Cellular and Molecular Biology of Esophageal Cancer

  • Alfred K. LamEmail author


The study of cellular and molecular biology in esophageal carcinomas serves the following purposes: (1) to establish the presence or absence of an infectious cofactor such as human papilloma virus; (2) to understand the genetic mechanisms of disease such as genetic mutations, changes in microRNAs, and the roles of cancer stem cells; (3) to provide prognostic information; and (4) to predict response to medical therapies and new modalities of treatment. In recent years, significant genomic information obtained from the whole genomic sequencing of prospectively collected frozen samples of esophageal carcinomas has opened the field for in-depth understanding of the complex molecular pathways underlying this cancer type. Anti-Her 2 therapy was approved internationally as targeted therapy for esophageal adenocarcinoma of the gastroesophageal junction. Assessment of Her 2 expression is currently the most important molecular test to be performed in clinical settings. The study of cellular and molecular biology of esophageal carcinomas depends on the proper collection of formalin-fixed and snap-frozen tissues as well as blood from patients. Tissue microarray and whole-slide scanning technologies allow tissue research in esophageal carcinomas to progress more efficiently. Cancer cell lines and animal models are valuable to study functional aspects of the various cellular and molecular changes in esophageal carcinomas.


Esophageal Squamous cell carcinoma Adenocarcinoma HPV Gene Prognosis TMA Pathology Cell lines Animal model Molecular biology 


  1. 1.
    Lam KY, Ma L. Pathology of esophageal cancers: local experience and current insights. Chin Med J. 1997;110:459–64.PubMedGoogle Scholar
  2. 2.
    Lam AKY. Critical review: molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol. 2000;33:71–90.PubMedCrossRefGoogle Scholar
  3. 3.
    Lam AK. Histopathological assessment for esophageal adenocarcinoma. Methods Mol Biol. 2018;1756:67–76.PubMedCrossRefGoogle Scholar
  4. 4.
    Lam KY, Law S, Tung PH, Wong J. Esophageal basaloid squamous cell carcinoma: an unique clinicopathological entity with telomerase activity as a prognostic indicator. J Pathol. 2001;195:435–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Lam KY, Law SYK, Loke SL, Fok M, Ma LT. Double sarcomatoid carcinomas of the esophagus. Pathol Res Pract. 1996;192:604–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Lam KY, Dickens P, Loke SL, Fok M, Ma L, Wong J. Squamous cell carcinoma of the esophagus with mucin-secreting component (mucoepidermoid carcinoma and adenosquamous cell carcinoma): a clinicopathologic study and a review of literature. Eur J Surg Oncol. 1994;20:25–31.PubMedGoogle Scholar
  7. 7.
    Law SYK, Fok M, Lam KY, Loke SL, Ma LT, Wong J. Small cell carcinoma of the esophagus. Cancer. 1994;73:2894–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Chow V, Law S, Lam KY, Luk JM, Wong J. Telomerase activity in small cell esophageal carcinoma. Dis Esophagus. 2001;14:139–42.PubMedCrossRefGoogle Scholar
  9. 9.
    Lam KY, Law S, Tung PH, Wong J. Esophageal small cell carcinoma: clinicopathologic parameters, p53 overexpression, proliferative marker, and their impact on pathogenesis. Arch Pathol Lab Med. 2000;124:228–33.PubMedGoogle Scholar
  10. 10.
    Lam AK. Introduction: esophageal adenocarcinoma: updates of current status. Methods Mol Biol. 1756;2018:1–6.Google Scholar
  11. 11.
    Juckett G, Hartman-Adams H. Human papillomavirus: clinical manifestations and prevention. Am Fam Physician. 2010;82:1209–13.PubMedGoogle Scholar
  12. 12.
    Husain N, Neyaz A. Human papillomavirus associated head and neck squamous cell carcinoma: controversies and new concepts. J Oral Biol Craniofac Res. 2017;7:198–205.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Shaikh MH, Khan AI, Sadat A, Chowdhury AH, Jinnah SA, Gopalan V, Lam AK, Clarke DTW, McMillan NAJ, Johnson NW. Prevalence and types of high-risk human papillomaviruses in head and neck cancers from Bangladesh. BMC Cancer. 2017;17:792.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    He D, Zhang DK, Lam KY, Ma L, Ngan HYS, Liu SS, Tsao SW. Prevalence of HPV infection in esophageal squamous cell carcinoma in Chinese patients and its relationship to the p53 gene mutation. Int J Cancer. 1997;72:959–64.PubMedCrossRefGoogle Scholar
  15. 15.
    Lam KY, He D, Ma L, Zhang D, Ngan HYS, Wan TSK, Tsao SW. Presence of human papillomavirus in esophageal squamous cell carcinomas of Hong Kong Chinese and its relationship with p53 gene mutation. Hum Pathol. 1997;28:657–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Li X, Gao C, Yang Y, Zhou F, Li M, Jin Q, Gao L. Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther. 2014;39:270–81.PubMedCrossRefGoogle Scholar
  17. 17.
    Rajendra S, Yang T, Xuan W, Sharma P, Pavey D, Lee CS, Le S, Collins J, Wang B. Active human papillomavirus involvement in Barrett’s dysplasia and oesophageal adenocarcinoma is characterized by wild-type p53 and aberrations of the retinoblastoma protein pathway. Int J Cancer. 2017;141:2037–49.PubMedCrossRefGoogle Scholar
  18. 18.
    Antonsson A, Knight L, Whiteman DC. Human papillomavirus not detected in esophageal adenocarcinoma tumor specimens. Cancer Epidemiol. 2016;41:96–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Löfdahl HE, Du J, Näsman A, Andersson E, Rubio CA, Lu Y, Ramqvist T, Dalianis T, Lagergren J, Dahlstrand H. Prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma in relation to anatomical site of the tumour. PLoS One. 2012;7:e46538.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Wang WJ, Wu MJ, Ren JL, Xie P, Chang J, Hu GM, Wu HF. p16INK4a is not a reliable screening marker of HPV infection in esophageal squamous cell carcinoma:evidence from a meta-analysis. Int J Biol Markers. 2016;31:e431–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Bucchi D, Stracci F, Buonora N, Masanotti G. Human papillomavirus and gastrointestinal cancer: a review. World J Gastroenterol. 2016;22:7415–30.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Xi R, Pan S, Chen X, Hui B, Zhang L, Fu S, Li X, Zhang X, Gong T, Guo J, Zhang X, Che S. HPV16 E6-E7 induces cancer stem-like cells phenotypes in esophageal squamous cell carcinoma through the activation of PI3K/Akt signaling pathway in vitro and in vivo. Oncotarget. 2016;7:57050–65.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Zhang D, Zhang W, Liu W, Mao Y, Fu Z, Liu J, Huang W, Zhang Z, An D, Li B. Human papillomavirus infection increases the chemoradiation response of esophageal squamous cell carcinoma based on P53 mutation. Radiother Oncol. 2017;124:155–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Wang WL, Wang YC, Lee CT, Chang CY, Lo JL, Kuo YH, Hsu YC, Mo LR. The impact of human papillomavirus infection on the survival and treatment response of patients with esophageal cancers. J Dig Dis. 2015;16:256–63.PubMedCrossRefGoogle Scholar
  25. 25.
    da Costa AM, Fregnani JHTG, Pastrez PRA, Mariano VS, Silva EM, Neto CS, Guimarães DP, Villa LL, Sichero L, Syrjanen KJ, Longatto-Filho A. HPV infection and p53 and p16 expression in esophageal cancer: are they prognostic factors? Infect Agent Cancer. 2017;12:54.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Pouyanfard S, Müller M. Human papillomavirus first and second generation vaccines-current status and future directions. Biol Chem. 2017;398:871–89.PubMedCrossRefGoogle Scholar
  27. 27.
    Al-Haddad S, El-Zimaity H, Hafezi-Bakhtiari S, Rajendra S, Streutker CJ, Vajpeyi R, Wang B. Infection and esophageal cancer. Ann N Y Acad Sci. 2014;1325:187–96.PubMedCrossRefGoogle Scholar
  28. 28.
    Lam KY, Srivastava G, Leung ML, Ma L. Absence of Epstein-Barr virus in esophageal squamous cell carcinoma: a study of 74 cases using in-situ hybridization. J Clin Pathol Mol Pathol. 1995;48:M188–90.CrossRefGoogle Scholar
  29. 29.
    Xu W, Liu Z, Bao Q, Qian Z. Viruses, other pathogenic microorganisms and esophageal cancer. Gastrointest Tumors. 2015;2:2–13.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Wang ZK, Yang YS. Upper gastrointestinal microbiota and digestive diseases. World J Gastroenterol. 2013;19:1541–50.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Gibson MK, Dhaliwal AS, Clemons NJ, Phillips WA, Dvorak K, Tong D, Law S, Pirchi ED, Räsänen J, Krasna MJ, Parikh K, Krishnadath KK, Chen Y, Griffiths L, Colleypriest BJ, Farrant JM, Tosh D, Das KM, Bajpai M. Barrett’s esophagus: cancer and molecular biology. Ann N Y Acad Sci. 2013;1300:296–314.PubMedCrossRefGoogle Scholar
  32. 32.
    Li B, Xu WW, Lam AKY, Wang Y, Hu HF, Guan XY, Qin YR, Saremi N, Tsao SW, He QY, Cheung ALM. Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy. Oncotarget. 2017;8:38755–66.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Yu VZ, Wong VC, Dai W, Ko JM, Lam AK, Chan KW, Samant RS, Lung HL, Shuen WH, Law S, Chan YP, Lee NP, Tong DK, Law TT, Lee VH, Lung ML. Nuclear localization of DNAJB6 is associated with survival of patients with esophageal cancer and reduces AKT signaling and proliferation of cancer cells. Gastroenterology. 2015;149:1825–36.PubMedCrossRefGoogle Scholar
  34. 34.
    Chung Y, Lam AK, Luk JM, Law S, Chan KW, Lee PY, Wong J. Altered E-cadherin expression and p120 catenin localization in esophageal squamous cell carcinoma. Ann Surg Oncol. 2007;14:3260–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Xu WW, Li B, Lam AK, Tsao SW, Law SY, Chan KW, Yuan QJ, Cheung AL. Targeting VEGFR1- and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy. Oncotarget. 2015;6:1790–805.PubMedGoogle Scholar
  36. 36.
    Chan D, Tsoi MY, Liu CD, Chan SH, Law SY, Chan KW, Chan YP, Gopalan V, Lam AK, Tang JC. Oncogene GAEC1 regulates CAPN10 expression which predicts survival in esophageal squamous cell carcinoma. World J Gastroenterol. 2013;19:2772–80.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Chai AW, Cheung AK, Dai W, Ko JM, Ip JC, Chan KW, Kwong DL, Ng WT, Lee AW, Ngan RK, Yau CC, Tung SY, Lee VH, Lam AK, Pillai S, Law S, Lung ML. Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma. Oncotarget. 2016;7:78859–71.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Lam KY, Tsao SW, Zhang D, Law S, He D, Ma L, Wong J. Prevalence and predictive value of p53 mutation in patients with esophageal squamous cell carcinomas: a prospective clinicopatholgical study and survival analysis of 70 patients. Int J Cancer. 1997;74:212–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Appelman HD, Matejcic M, Parker MI, Riddell RH, Salemme M, Swanson PE, Villanacci V. Progression of esophageal dysplasia to cancer. Ann N Y Acad Sci. 2014;1325:96–107.PubMedCrossRefGoogle Scholar
  40. 40.
    Lee KTW, Gopalan V, Lam AK. Somatic DNA copy number alterations detection for oesophageal adenocarcinoma using digital polymerase chain reaction. Methods Mol Biol. 2018;1756:195–212.PubMedCrossRefGoogle Scholar
  41. 41.
    Islam F, Tang JC, Gopalan V, Lam AK. Epigenetics: DNA methylation analysis in esophageal adenocarcinoma. Methods Mol Biol. 2018;1756:247–56.PubMedCrossRefGoogle Scholar
  42. 42.
    Haque MH, Islam MN, Islam F, Gopalan V, Nguyen NT, Lam AK, Shiddiky MJ. Electrochemical detection of FAM134B mutations in oesophageal cancer based on DNA-gold affinity interactions. Electroanalysis. 2017;29:1359–67.CrossRefGoogle Scholar
  43. 43.
    Haque MH, Gopalan V, Islam MN, Masud MK, Bhattacharjee R, Hossain MSA, Nguyen NT, Lam AK, Shiddiky MJA. Quantification of gene-specific DNA methylation in oesophageal cancer via electrochemistry. Anal Chim Acta. 2017;976:84–93.PubMedCrossRefGoogle Scholar
  44. 44.
    Pack SD, Karkera JD, Zhuang Z, Pak ED, Balan KV, Hwu P, Park WS, Pham T, Ault DO, Glaser M, Liotta L, Detera-Wadleigh SD, Wadleigh RG. Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations. Genes Chromosomes Cancer. 1999;25:160–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Walch AK, Zitzelsberger HF, Bruch J, Keller G, Angermeier D, Aubele MM, Mueller J, Stein H, Braselmann H, Siewert JR, Höfler H, Werner M. Chromosomal imbalances in Barrett’s adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence. Am J Pathol. 2000;156:555–66.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Kwong D, Lam A, Guan X, Law S, Tai A, Wong J, Sham J. Chromosomal aberrations in esophageal squamous cell carcinoma among Chinese: gain of 12p predicts poor prognosis after surgery. Hum Pathol. 2004;35:309–16.PubMedCrossRefGoogle Scholar
  47. 47.
    Qin YR, Wang LD, Fan ZM, Kwong D, Guan XY. Comparative genomic hybridization analysis of genetic aberrations associated with development of esophageal squamous cell carcinoma in Henan, China. World J Gastroenterol. 2008;14:1828–35.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Tang JCO, Lam KY, Law S, Wong J, Srivastava G. Detection of genetic alterations in esophageal squamous cell carcinomas and adjacent normal epithelia by comparative DNA fingerprinting using inter-simple sequence repeat PCR. Clin Cancer Res. 2001;7:1539–45.PubMedGoogle Scholar
  49. 49.
    Hu YC, Lam KY, Law S, Wong J, Srivastava G. Identification of differentially expressed in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1 and CDC25B genes in ESCC. Clin Cancer Res. 2001;7:2213–21.PubMedGoogle Scholar
  50. 50.
    Fatima S, Chui CH, Tang WK, Hui KS, Au HW, Li WY, Wong MM, Cheung F, Tsao SW, Lam KY, Beh PS, Wong J, Law S, Srivastava G, Ho KP, Chan AS, Tang JC. Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma. Int J Mol Med. 2006;17:159–70.PubMedGoogle Scholar
  51. 51.
    Tang WK, Chui CH, Fatima S, Kok SH, Pak KC, Ou TM, Hui KS, Wong MM, Wong J, Law S, Tsao SW, Lam KY, Beh PS, Srivastava G, Chan AS, Ho KP, Tang JC. Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma. Int J Mol Med. 2007;19:915–23.PubMedGoogle Scholar
  52. 52.
    Goh XY, Rees JR, Paterson AL, Chin SF, Marioni JC, Save V, O’Donovan M, Eijk PP, Alderson D, Ylstra B, Caldas C, Fitzgerald RC. Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma. Gut. 2011;60:1317–26.PubMedCrossRefGoogle Scholar
  53. 53.
    Law FB, Chen YW, Wong KY, Ying J, Tao Q, Langford C, Lee PY, Law S, Cheung RW, Chui CH, Tsao SW, Lam KY, Wong J, Srivastava G, Tang JC. Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma. Oncogene. 2007;26:5877–88.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Haque MH, Gopalan V, Chan KW, Shiddiky MJ, Smith RA, Lam AK. Identification of novel FAM134B (JK1) mutations in oesophageal squamous cell carcinoma. Sci Rep. 2016;6:29173.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Lee KT, Smith RA, Gopalan V, Lam AK. Targeted single gene mutation in oesophageal adenocarcinoma. Methods Mol Biol. 1756;2018:213–29.Google Scholar
  56. 56.
    Pillai S, Gopalan V, Lam AK. DNA genome sequencing in oesophageal adenocarcinoma. Methods Mol Biol. 2018;1756:231–46.PubMedCrossRefGoogle Scholar
  57. 57.
    Pillai S, Gopalan V, Lam AK. Review of sequencing platforms and their applications in phaeochromocytoma and paragangliomas. Crit Rev Oncol Hematol. 2017;116:58–67.PubMedCrossRefGoogle Scholar
  58. 58.
    Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, Meng X, Sato Y, Okuno Y, Varela AM, Ding LW, Garg M, Liu LZ, Yang H, Yin D, Shi ZZ, Jiang YY, Gu WY, Gong T, Zhang Y, Xu X, Kalid O, Shacham S, Ogawa S, Wang MR, Koeffler HP. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet. 2014;46:467–73.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Wang Q, Bai J, Abliz A, Liu Y, Gong K, Li J, Shi W, Pan Y, Liu F, Lai S, Yang H, Lu C, Zhang L, Chen W, Xu R, Cai H, Ke Y, Zeng C. An old story retold: loss of G1 control defines a distinct genomic subtype of esophageal squamous cell carcinoma. Genomics Proteomics Bioinformatics. 2015;13:258–70.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Stachler MD, Taylor-Weiner A, Peng S, McKenna A, Agoston AT, Odze RD, Davison JM, Nason KS, Loda M, Leshchiner I, Stewart C, Stojanov P, Seepo S, Lawrence MS, Ferrer-Torres D, Lin J, Chang AC, Gabriel SB, Lander ES, Beer DG, Getz G, Carter SL, Bass AJ. Paired exome analysis of Barrett’s esophagus and adenocarcinoma. Nat Genet. 2015;47:1047–55.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Rajendra S, Wang B, Merrett N, Sharma P, Humphris J, Lee HC, Wu J. Genomic analysis of HPV-positive versus HPV-negative oesophageal adenocarcinoma identifies a differential mutational landscape. J Med Genet. 2016;53:227–31.PubMedCrossRefGoogle Scholar
  62. 62.
    Findlay JM, Castro-Giner F, Makino S, Rayner E, Kartsonaki C, Cross W, Kovac M, Ulahannan D, Palles C, Gillies RS, MacGregor TP, Church D, Maynard ND, Buffa F, Cazier JB, Graham TA, Wang LM, Sharma RA, Middleton M, Tomlinson I. Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy. Nat Commun. 2016;7:11111.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Liu W, Snell JM, Jeck WR, Hoadley KA, Wilkerson MD, Parker JS, Patel N, Mlombe YB, Mulima G, Liomba NG, Wolf LL, Shores CG, Gopal S, Sharpless NE. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis. JCI Insight. 2016;1:e88755.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Hao JJ, Lin DC, Dinh HQ, Mayakonda A, Jiang YY, Chang C, Jiang Y, Lu CC, Shi ZZ, Xu X, Zhang Y, Cai Y, Wang JW, Zhan QM, Wei WQ, Berman BP, Wang MR, Koeffler HP. Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma. Nat Genet. 2016;48:1500–7.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Chen XX, Zhong Q, Liu Y, Yan SM, Chen ZH, Jin SZ, Xia TL, Li RY, Zhou AJ, Su Z, Huang YH, Huang QT, Huang LY, Zhang X, Zhao YN, Yun JP, Wu QL, Lin DX, Bai F, Zeng MS. Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing. Nat Commun. 2017;8:524.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Forouzanfar N, Baranova A, Milanizadeh S, Heravi-Moussavi A, Jebelli A, Abbaszadegan MR. Novel candidate genes may be possible predisposing factors revealed by whole exome sequencing in familial esophageal squamous cell carcinoma. Tumour Biol. 2017;39:1010428317699115.PubMedCrossRefGoogle Scholar
  67. 67.
    Dai W, Ko JMY, Choi SSA, Yu Z, Ning L, Zheng H, Gopalan V, Chan KT, Lee NP, Chan KW, Law SY, Lam AK, Lung ML. Whole-exome sequencing reveals critical genes underlying metastasis in oesophageal squamous cell carcinoma. J Pathol. 2017;242:500–10.PubMedCrossRefGoogle Scholar
  68. 68.
    Zhang J, Baran J, Cros A, Guberman JM, Haider S, Hsu J, Liang Y, Rivkin E, Wang J, Whitty B, Wong-Erasmus M, Yao L, Kasprzyk A. International cancer genome consortium data portal—a one-stop shop for cancer genomics data. Database (Oxford). 2011;2011:bar026.Google Scholar
  69. 69.
    Dulak AM, Stojanov P, Peng S, Lawrence MS, Fox C, Stewart C, Bandla S, Imamura Y, Schumacher SE, Shefler E, McKenna A, Carter SL, Cibulskis K, Sivachenko A, Saksena G, Voet D, Ramos AH, Auclair D, Thompson K, Sougnez C, Onofrio RC, Guiducci C, Beroukhim R, Zhou Z, Lin L, Lin J, Reddy R, Chang A, Landrenau R, Pennathur A, Ogino S, Luketich JD, Golub TR, Gabriel SB, Lander ES, Beer DG, Godfrey TE, Getz G, Bass AJ. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45:478–86.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Song Y, Li L, Ou Y, Gao Z, Li E, Li X, Zhang W, Wang J, Xu L, Zhou Y, Ma X, Liu L, Zhao Z, Huang X, Fan J, Dong L, Chen G, Ma L, Yang J, Chen L, He M, Li M, Zhuang X, Huang K, Qiu K, Yin G, Guo G, Feng Q, Chen P, Wu Z, Wu J, Ma L, Zhao J, Luo L, Fu M, Xu B, Chen B, Li Y, Tong T, Wang M, Liu Z, Lin D, Zhang X, Yang H, Wang J, Zhan Q. Identification of genomic alterations in oesophageal squamous cell cancer. Nature. 2014;509:91–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, MCJ Q, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, TJC B, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderson M, Kazakoff S, Leonard C, Wood S, Simpson PT, Reid LE, Krause L, Hussey DJ, Watson DI, Lord RV, Nancarrow D, Phillips WA, Gotley D, Smithers BM, Whiteman DC, Hayward NK, Campbell PJ, Pearson JV, Grimmond SM, Barbour AP. Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun. 2014;5:5224.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Weaver JMJ, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, Barbera M, Murtaza M, Ong CJ, Lao-Sirieix P, Dunning MJ, Smith L, Smith ML, Anderson CL, Carvalho B, O’Donovan M, Underwood TJ, May AP, Grehan N, Hardwick R, Davies J, Oloumi A, Aparicio S, Caldas C, Eldridge MD, PAW E, Rosenfeld N, Tavaré S, Fitzgerald RC, OCCAMS consortium. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet. 2014;46:837–43.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Paterson AL, Weaver JM, Eldridge MD, Tavaré S, Fitzgerald RC, Edwards PA, OCCAMs Consortium. Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired-end sequencing analysis. BMC Genomics. 2015;16:473.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Ross-Innes CS, Becq J, Warren A, Cheetham RK, Northen H, O’Donovan M, Malhotra S, di Pietro M, Ivakhno S, He M, Weaver JMJ, Lynch AG, Kingsbury Z, Ross M, Humphray S, Bentley D, Fitzgerald RC. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma. Nat Genet. 2015;47:1038–46.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Zhang L, Zhou Y, Cheng C, Cui H, Cheng L, Kong P, Wang J, Li Y, Chen W, Song B, Wang F, Jia Z, Li L, Li Y, Yang B, Liu J, Shi R, Bi Y, Zhang Y, Wang J, Zhao Z, Hu X, Yang J, Li H, Gao Z, Chen G, Huang X, Yang X, Wan S, Chen C, Li B, Tan Y, Chen L, He M, Xie S, Li X, Zhuang X, Wang M, Xia Z, Luo L, Ma J, Dong B, Zhao J, Song Y, Ou Y, Li E, Xu L, Wang J, Xi Y, Li G, Xu E, Liang J, Yang X, Guo J, Chen X, Zhang Y, Li Q, Liu L, Li Y, Zhang X, Yang H, Lin D, Cheng X, Guo Y, Wang J, Zhan Q, Cui Y. Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma. Am J Hum Genet. 2015;96:597–611.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Qin HD, Liao XY, Chen YB, Huang SY, Xue WQ, Li FF, Ge XS, Liu DQ, Cai Q, Long J, Li XZ, Hu YZ, Zhang SD, Zhang LJ, Lehrman B, Scott AF, Lin D, Zeng YX, Shugart YY, Jia WH. Genomic characterization of esophageal squamous cell carcinoma reveals critical genes underlying tumorigenesis and poor prognosis. Am J Hum Genet. 2016;98:709–27.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Sawada G, Niida A, Uchi R, Hirata H, Shimamura T, Suzuki Y, Shiraishi Y, Chiba K, Imoto S, Takahashi Y, Iwaya T, Sudo T, Hayashi T, Takai H, Kawasaki Y, Matsukawa T, Eguchi H, Sugimachi K, Tanaka F, Suzuki H, Yamamoto K, Ishii H, Shimizu M, Yamazaki H, Yamazaki M, Tachimori Y, Kajiyama Y, Natsugoe S, Fujita H, Mafune K, Tanaka Y, Kelsell DP, Scott CA, Tsuji S, Yachida S, Shibata T, Sugano S, Doki Y, Akiyama T, Aburatani H, Ogawa S, Miyano S, Mori M, Mimori K. Genomic landscape of esophageal squamous cell carcinoma in a Japanese population. Gastroenterology. 2016;150:1171–82.PubMedCrossRefGoogle Scholar
  78. 78.
    Secrier M, Li X, de Silva N, Eldridge MD, Contino G, Bornschein J, MacRae S, Grehan N, O’Donovan M, Miremadi A, Yang TP, Bower L, Chettouh H, Crawte J, Galeano-Dalmau N, Grabowska A, Saunders J, Underwood T, Waddell N, Barbour AP, Nutzinger B, Achilleos A, Edwards PA, Lynch AG, Tavaré S, Fitzgerald RC, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance. Nat Genet. 2016;48:1131–41.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Cheng C, Zhou Y, Li H, Xiong T, Li S, Bi Y, Kong P, Wang F, Cui H, Li Y, Fang X, Yan T, Li Y, Wang J, Yang B, Zhang L, Jia Z, Song B, Hu X, Yang J, Qiu H, Zhang G, Liu J, Xu E, Shi R, Zhang Y, Liu H, He C, Zhao Z, Qian Y, Rong R, Han Z, Zhang Y, Luo W, Wang J, Peng S, Yang X, Li X, Li L, Fang H, Liu X, Ma L, Chen Y, Guo S, Chen X, Xi Y, Li G, Liang J, Yang X, Guo J, Jia J, Li Q, Cheng X, Zhan Q, Cui Y. Whole-genome sequencing reveals diverse models of structural variations in esophageal squamous cell carcinoma. Am J Hum Genet. 2016;98:256–74.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Cheng C, Cui H, Zhang L, Jia Z, Song B, Wang F, Li Y, Liu J, Kong P, Shi R, Bi Y, Yang B, Wang J, Zhao Z, Zhang Y, Hu X, Yang J, He C, Zhao Z, Wang J, Xi Y, Xu E, Li G, Guo S, Chen Y, Yang X, Chen X, Liang J, Guo J, Cheng X, Wang C, Zhan Q, Cui Y. Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma. Gigascience. 2016;5:1.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Fels Elliott DR, Perner J, Li X, Symmons MF, Verstak B, Eldridge M, Bower L, O’Donovan M, Gay NJ, OCCAMS Consortium, Fitzgerald RC. Impact of mutations in toll-like receptor pathway genes on esophageal carcinogenesis. PLoS Genet. 2017;13:e1006808.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Noorani A, Bornschein J, Lynch AG, Secrier M, Achilleos A, Eldridge M, Bower L, Weaver JMJ, Crawte J, Ong CA, Shannon N, MacRae S, Grehan N, Nutzinger B, O’Donovan M, Hardwick R, Tavaré S. Fitzgerald RC; oesophageal cancer clinical and molecular stratification (OCCAMS) consortium. A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy. Genome Res. 2017;27:902–12.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Liu X, Zhang M, Ying S, Zhang C, Lin R, Zheng J, Zhang G, Tian D, Guo Y, Du C, Chen Y, Chen S, Su X, Ji J, Deng W, Li X, Qiu S, Yan R, Xu Z, Wang Y, Guo Y, Cui J, Zhuang S, Yu H, Zheng Q, Marom M, Sheng S, Zhang G, Hu S, Li R, Su M. Genetic alterations in esophageal tissues from squamous dysplasia to carcinoma. Gastroenterology. 2017;153:166–77.PubMedCrossRefGoogle Scholar
  84. 84.
    Mamoori A, Wahab R, Islam F, Lee K, Vider J, Lu CT, Gopalan V, Lam AK. Clinical and biological significance of miR-193a-3p targeted KRAS in colorectal cancer pathogenesis. Hum Pathol. 2018;71:145–56.PubMedCrossRefGoogle Scholar
  85. 85.
    Mamoori A, Gopalan V, Lu CT, Chua TC, Morris DL, Smith RA, Lam AK. Expression pattern of miR-451 and its target MIF (macrophage migration inhibitory factor) in colorectal cancer. J Clin Pathol. 2017;70:308–12.PubMedCrossRefGoogle Scholar
  86. 86.
    Pillai S, Lo CY, Liew V, Lalloz M, Smith RA, Gopalan V, Lam AK. microRNA 183 family profiles in pheochromocytomas are related to clinical parameters and SDHB expression. Hum Pathol. 2017;64:91–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Islam F, Gopalan V, Vider J, Wahab R, Ebrahimi F, Lu CT, Kasem K, Lam AKY. MicroRNA-186-5p overexpression modulates colon cancer growth by repressing the expression of the FAM134B tumour inhibitor. Exp Cell Res. 2017;357:260–70.PubMedCrossRefGoogle Scholar
  88. 88.
    Lee KT, Tan JK, Lam AK, Gan SY. MicroRNAs serving as potential biomarkers and therapeutic targets in nasopharyngeal carcinoma: a critical review. Crit Rev Oncol Hematol. 2016;103:1–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Gopalan V, Smith RA, Lam AK. Downregulation of microRNA-498 in colorectal cancers and its cellular effects. Exp Cell Res. 2015;330:423–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Salajegheh A, Vosgha H, Md Rahman A, Amin M, Smith RA, Lam A. Modulatory role of miR-205 in angiogenesis and progression of thyroid cancer. J Mol Endocrinol. 2015;55:183–96.PubMedCrossRefGoogle Scholar
  91. 91.
    Ebrahimi F, Gopalan V, Wahab R, Lu CT, Anthony Smith R, Lam AK. Deregulation of miR-126 expression in colorectal cancer pathogenesis and its clinical significance. Exp Cell Res. 2015;339:333–41.PubMedCrossRefGoogle Scholar
  92. 92.
    Gopalan V, Pillai S, Ebrahimi F, Salajegheh A, Lam TC, Le TK, Langsford N, Ho YH, Smith RA, Lam AK. Regulation of microRNA-1288 in colorectal cancer: altered expression and its clinicopathological significance. Mol Carcinog. 2014;53:E36–44.PubMedCrossRefGoogle Scholar
  93. 93.
    Ebrahimi F, Gopalan V, Smith RA, Lam AK. miR-126 in human cancers: clinical roles and current perspectives. Exp Mol Pathol. 2014;96:98–107.PubMedCrossRefGoogle Scholar
  94. 94.
    Maroof H, Salajegheh A, Smith RA, Lam AK. Role of microRNA-34 family in cancer with particular reference to cancer angiogenesis. Exp Mol Pathol. 2014;97:298–304.PubMedCrossRefGoogle Scholar
  95. 95.
    Vosgha H, Salajegheh A, Smith RA, Lam AK. The important roles of miR-205 in normal physiology, cancers and as a potential therapeutic target. Curr Cancer Drug Targets. 2014;14:621–37.PubMedCrossRefGoogle Scholar
  96. 96.
    Maroof H, Salajegheh A, Smith RA, Lam AK. MicroRNA-34 family, mechanisms of action in cancer: a review. Curr Cancer Drug Targets. 2014;14:737–51.PubMedCrossRefGoogle Scholar
  97. 97.
    Amin M, Islam F, Gopalan V, Lam AK. Detection and quantification of microRNAs in in oesophageal adenocarcinoma. Methods Mol Biol. 1756;2018:257–68.Google Scholar
  98. 98.
    Kamal Masud M, Islam MN, Haque MH, Tanaka S, Gopalan V, Alici G, Nguyen NT, Lam AK, Hossain MSA, Yamauchi Y, Shiddiky MJA. Gold-loaded nanoporous superparamagnetic nanocubes for catalytic signal amplification in detecting miRNA. Chem Commun (Camb). 2017;53:8231–4.CrossRefGoogle Scholar
  99. 99.
    Amin M, Lam AK. Current perspectives of mi-RNA in oesophageal adenocarcinoma: roles in predicting carcinogenesis, progression and values in clinical management. Exp Mol Pathol. 2015;98:411–8.PubMedCrossRefGoogle Scholar
  100. 100.
    Mei LL, Qiu YT, Zhang B, Shi ZZ. MicroRNAs in esophageal squamous cell carcinoma: potential biomarkers and therapeutic targets. Cancer Biomark. 2017;19:1–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Islam F, Gopalan V, Law S, Tang JC, Chan KW. Lam AK∗. MiR-498 in oesophageal squamous cell carcinoma: clinicopathological impacts and functional interactions. Hum Pathol. 2017;62:141–51.PubMedCrossRefGoogle Scholar
  102. 102.
    Gopalan V, Islam F, Pillai S, Tang JC, Tong DK, Law S, Chan KW, Lam AK. Overexpression of microRNA-1288 in oesophageal squamous cell carcinoma. Exp Cell Res. 2016;348:146–54.PubMedCrossRefGoogle Scholar
  103. 103.
    Islam F, Qiao B, Smith RA, Gopalan V, Lam AK. Cancer stem cell: fundamental experimental pathological concepts and updates. Exp Mol Pathol. 2015;98:184–91.PubMedCrossRefGoogle Scholar
  104. 104.
    Wahab SMR, Islam F, Gopalan V, Lam AK. The identifications and clinical implications of cancer stem cells in colorectal cancer. Clin Colorectal Cancer. 2017;16:93–102.PubMedCrossRefGoogle Scholar
  105. 105.
    Islam F, Gopalan V, Smith RA, Lam AK. Translational potential of cancer stem cells: a review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment. Exp Cell Res. 2015;335:135–47.PubMedCrossRefGoogle Scholar
  106. 106.
    Chruścik A, Gopalan V, Lam AK. The clinical and biological roles of transforming growth factor beta in colon cancer stem cells: a systematic review. Eur J Cell Biol. 2018;97:15–22.PubMedCrossRefGoogle Scholar
  107. 107.
    Qiao B, Gopalan V, Chen Z, Smith RA, Tao Q, Lam AKY. Epithelial-mesenchymal transition and mesenchymal-epithelial transition are essential for the acquisition of stem cell properties in hTERT-immortalised oral epithelial cells. Bio Cell. 2012;104:476–89.CrossRefGoogle Scholar
  108. 108.
    Gopalan V, Islam F, Lam AK. Surface markers for the identification of cancer stem cells. Methods Mol Biol. 1692;2018:17–29.Google Scholar
  109. 109.
    Islam F, Gopalan V, Wahab R, Smith RA, Lam AK. Cancer stem cells in oesophageal squamous cell carcinoma: identification, prognostic and treatment perspectives. Crit Rev Oncol Hematol. 2015;96:9–19.PubMedCrossRefGoogle Scholar
  110. 110.
    Islam F, Gopalan V, Lam AK. Identification of cancer stem cells in esophageal adenocarcinoma. Methods Mol Biol. 2018;1756:165–76.PubMedCrossRefGoogle Scholar
  111. 111.
    di Pietro M, Alzoubaidi D, Fitzgerald RC. Barrett’s esophagus and cancer risk: how research advances can impact clinical practice. Gut Liver. 2014;8:356–70.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Ong CAJ, Lao-Sirieix P, Fitzgerald RC. Biomarkers in Barrett’s esophagus and esophageal adenocarcinoma: predictors of progression and prognosis. World J Gastroenterol. 2010;16:5669–81.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Chen M, Huang J, Zhu Z, Zhang J, Li K. Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer. BMC Cancer. 2013;13:539.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Shang L, Liu HJ, Hao JJ, Jiang YY, Shi F, Zhang Y, Cai Y, Xu X, Jia XM, Zhan QM, Wang MR. A panel of overexpressed proteins for prognosis in esophageal squamous cell carcinoma. PLoS One. 2014;9:e111045.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Lam KY, Law S, Lo T, Tung HM, Wong J. The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients. Am J Gastroenterol. 1999;94:2060–8.PubMedCrossRefGoogle Scholar
  116. 116.
    Lam KY, Law SYK, So MKP, Fok M, Ma LT, Wong J. Prognostic implication of proliferative markers MIB-1 and PC 10 in esophageal squamous cell carcinoma. Cancer. 1996;77:7–13.PubMedCrossRefGoogle Scholar
  117. 117.
    Tong DK, Law S, Kwong DL, Chan KW, Lam AK, Wong KH. Histological regression of squamous esophageal carcinoma assessed by percentage of residual viable cells after neoadjuvant chemoradiation is an important prognostic factor. Ann Surg Oncol. 2010;17:2184–92.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Lam KY, Law S, Ma LT, Ong SK, Wong J. Pre-operative chemotherapy for squamous cell carcinoma of the esophagus: do histological assessment and p53 overexpression predict chemo-responsiveness? Eur J Cancer. 1997;33:1221–5.PubMedCrossRefGoogle Scholar
  119. 119.
    Okumura H, Uchikado Y, Setoyama T, Matsumoto M, Owaki T, Ishigami S, Natsugoe S. Biomarkers for predicting the response of esophageal squamous cell carcinoma to neoadjuvant chemoradiation therapy. Surg Today. 2014;44:421–8.PubMedCrossRefGoogle Scholar
  120. 120.
    Zhang SS, Huang QY, Yang H, Xie X, Luo KJ, Wen J, Cai XL, Yang F, Hu Y, Fu JH. Correlation of p53 status with the response to chemotherapy-based treatment in esophageal cancer: a meta-analysis. Ann Surg Oncol. 2013;20:2419–27.PubMedCrossRefGoogle Scholar
  121. 121.
    Bain GH, Petty RD. Predicting response to treatment in gastroesophageal junction adenocarcinomas: combining clinical, imaging, and molecular biomarkers. Oncologist. 2010;15:270–84.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Imdahl A, Jenkner J, Ihling C, Rückauer K, Farthmann EH. Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer? Am J Surg. 2000;179:514–20.PubMedCrossRefGoogle Scholar
  123. 123.
    Lam AK. Application of pathological staging in esophageal adenocarcinoma. Methods Mol Biol. 2018;1756:93–103.PubMedCrossRefGoogle Scholar
  124. 124.
    Ung L, Lam AK, Morris DL, Chua TC. Tissue-based biomarkers predicting outcomes in metastatic colorectal cancer: a review. Clin Transl Oncol. 2014;16:425–35.PubMedCrossRefGoogle Scholar
  125. 125.
    Pakneshan S, Salajegheh A, Smith RA, Lam AK. Clinicopathological relevance of BRAF mutations in human cancer. Pathology. 2013;45:346–56.PubMedCrossRefGoogle Scholar
  126. 126.
    Rahman MA, Salajegheh A, Smith RA, Lam AK. BRAF inhibitors: from the laboratory to clinical trials. Crit Rev Oncol Hematol. 2014;90:220–32.PubMedCrossRefGoogle Scholar
  127. 127.
    Rahman MA, Salajegheh A, Smith RA, Lam AK. BRAF inhibitor therapy for melanoma, thyroid and colorectal cancers: development of resistance and future prospects. Curr Cancer Drug Targets. 2014;14:128–43.PubMedCrossRefGoogle Scholar
  128. 128.
    O’Sullivan CC, Connolly RM. Pertuzumab and its accelerated approval: evolving treatment paradigms and new challenges in the management of HER2-positive breast cancer. Oncology (Williston Park). 2014;28:186–94.Google Scholar
  129. 129.
    Wiedmann MW, Mössner J. New and emerging combination therapies for esophageal cancer. Cancer Manag Res. 2013;5:133–46.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Kordes S, Cats A, Meijer SL, van Laarhoven HW. Targeted therapy for advanced esophagogastric adenocarcinoma. Crit Rev Oncol Hematol. 2014;90:68–76.PubMedCrossRefGoogle Scholar
  131. 131.
    Orditura M, Galizia G, Fabozzi A, Lieto E, Gambardella V, Morgillo F, Del Genio GM, Fei L, Di Martino N, Renda A, Ciardiello F, De Vita F. Preoperative treatment of locally advanced esophageal carcinoma (review). Int J Oncol. 2013;43:1745–53.PubMedCrossRefGoogle Scholar
  132. 132.
    Nakajima M, Kato H. Treatment options for esophageal squamous cell carcinoma. Expert Opin Pharmacother. 2013;14:1345–54.PubMedCrossRefGoogle Scholar
  133. 133.
    Boland PM, Burtness B. Esophageal carcinoma: are modern targeted therapies shaking the rock? Curr Opin Oncol. 2013;25:417–24.PubMedCrossRefGoogle Scholar
  134. 134.
    Lam KY, Tin L, Ma L. C-erbB-2 protein expression in oesophageal squamous epithelium from oesophageal squamous cell carcinomas, with special reference to histological grade of carcinoma and pre-invasive lesions. Eur J Surg Oncol. 1998;24:431–5.PubMedCrossRefGoogle Scholar
  135. 135.
    Hicks DG, Whitney-Miller C. HER2 testing in gastric and gastroesophageal junction cancers: a new therapeutic target and diagnostic challenge. Appl Immunohistochem Mol Morphol. 2011;19:506–8.PubMedCrossRefGoogle Scholar
  136. 136.
    Bartley AN, Washington MK, Colasacco C, Ventura CB, Ismaila N, Benson AB 3rd, Carrato A, Gulley ML, Jain D, Kakar S, Mackay HJ, Streutker C, Tang L, Troxell M, Ajani JA. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35:446–64.PubMedCrossRefGoogle Scholar
  137. 137.
    Kumarasinghe MP, Brown I, Raftopoulos S, Bourke MJ, Charlton A, de Boer WB, Eckstein R, Epari K, Gill AJ, Lam AK, Price T, Streutker C, Lauwers GY. Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations. Pathology. 2014;46:473–80.PubMedCrossRefGoogle Scholar
  138. 138.
    Saremi N, Lam AK. Application of tissue microarray in esophageal adenocarcinoma. In: Lam AK, editor. Methods in molecular biology: esophageal adenocarcinoma: Springer; 2018. (in press).Google Scholar
  139. 139.
    Lam AK, Leung M. Whole-slide imaging for esophageal adenocarcinoma. Methods Mol Biol. 2018;1756:135–42.PubMedCrossRefGoogle Scholar
  140. 140.
    Gopalan V, Lam AK. Circulatory tumor cells in esophageal adenocarcinoma. Methods Mol Biol. 2018;1756:177–86.PubMedCrossRefGoogle Scholar
  141. 141.
    Smith RA, Lam AK. Liquid biopsy for investigation of cancer DNA in oesophageal adenocarcinoma: cell free plasma DNA and exosome associated DNA. Methods Mol Biol. 2018;1756:187–94.PubMedCrossRefGoogle Scholar
  142. 142.
    Islam F, Gopalan V. Lam AK. RNA interference mediated genes silencing in oesophageal adenocarcinoma. Methods Mol Biol. 2018;1756:269–79.PubMedCrossRefGoogle Scholar
  143. 143.
    Tang JCO, Wan TSK, Wong N, Pang E, Lam KY, Law SYK, Chow LMC, Ma ESK, Chan LC, Wong J, Srivastava G. Establishment and characterization of a new xenograft-derived human esophageal squamous cell line SLMT-1 of Chinese origin. Cancer Genet Cytogenet. 2001;124:36–41.PubMedCrossRefGoogle Scholar
  144. 144.
    Hu YC, Lam KY, Wan TSK, Fang WG, Ma ESK, Chan LC, Srivastava G. Establishment and characterization of HKESC-1, a new cancer cell line from human esophageal squamous cell carcinoma. Cancer Genet Cytogenet. 2000;118:112–20.PubMedCrossRefGoogle Scholar
  145. 145.
    Hu YC, Lam KY, Law SYK, Wan TSK, Ma ESK, Kwong YL, Chan LC, Wong J, Srivastava G. Establishment, characterization, karyotyping, and comparative genomic hybridization analysis of HKESC-2 and HKESC-3: two newly established human esophageal squamous cell lines. Cancer Genet Cytogenet. 2002;135:120–7.PubMedCrossRefGoogle Scholar
  146. 146.
    Boonstra JJ, Tilanus HW, Dinjens WN. Translational research on esophageal adenocarcinoma: from cell line to clinic. Dis Esophagus. 2015;28:90–6.PubMedCrossRefGoogle Scholar
  147. 147.
    Ip JC, Ko JM, Yu VZ, Chan KW, Lam AK, Law S, Tong DK, Lung ML. A versatile orthotopic nude mouse model for study of esophageal squamous cell carcinoma. Biomed Res Int. 2015;2015:910715.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Furihata T, Sakai T, Kawamata H, Omotehara F, Shinagawa Y, Imura J, Ueda Y, Kubota K, Fujimori T. A new in vivo model for studying invasion and metastasis of esophageal squamous cell carcinoma. Int J Oncol. 2001;19:903–7.PubMedGoogle Scholar
  149. 149.
    Hori T, Yamashita Y, Ohira M, Matsumura Y, Muguruma K, Hirakawa K. A novel orthotopic implantation model of human esophageal carcinoma in nude rats: CD44H mediates cancer cell invasion in vitro and in vivo. Int J Cancer. 2001;92:489–96.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.School of MedicineGriffith University and Pathology Queensland, Gold Coast University HospitalGold CoastAustralia

Personalised recommendations