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Molecular Cytology of Serous Effusions

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Molecular Applications in Cytology

Abstract

Serous effusions are commonly encountered cytology specimens and are often submitted with the clinical suspicion of malignancy. The myriad cancers affecting this anatomic site may present a challenge in terms of differential diagnosis. Once recognized, the presence of metastasis within the serosal cavities, most often from carcinomas of the lung, breast, genital tract, or gastrointestinal tract, carries grave clinical implications, as disease at this anatomic site cannot be surgically removed. Therapeutic strategies must therefore include alternative approaches. In recent years, targeted therapy has assumed an increasing role in the management of metastatic cancer, including that of tumors affecting the serosal cavities. Additionally, high-throughput methodology has improved our understanding of the biology and disease progression of specific cancers at this anatomic site. This chapter discusses the molecular tests that have in recent years been applied to effusions and bear on specimen diagnosis and patient management.

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References

  1. Davidson B, Firat P, Michael CW, editors. Serous effusions. London: Springer; 2011.

    Google Scholar 

  2. Davidson B. Serous effusions. In: Bartlett JMS, Shabaan A, Schmitt F, editors. Molecular pathology: a practical guide for the surgical pathologist and cytopathologist. Cambridge: Cambridge University Press; 2015. p. 356–72.

    Google Scholar 

  3. Han J, Cao S, Zhang K, et al. Fluorescence in situ hybridization as adjunct to cytology improves the diagnosis and directs estimation of prognosis of malignant pleural effusions. J Cardiothorac Surg. 2012;7:121.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rosolen DC, Kulikowski LD, Bottura G, et al. Efficacy of two fluorescence in situ hybridization (FISH) probes for diagnosing malignant pleural effusions. Lung Cancer. 2013;80:284–8.

    Article  PubMed  Google Scholar 

  5. Fiegl M, Massoner A, Haun M, et al. Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH). Br J Cancer. 2004;91:558–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Illei PB, Ladanyi M, Rusch VW, et al. The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions. Cancer. 2003;99:51–6.

    Article  CAS  Google Scholar 

  7. Matsumoto S, Nabeshima K, Kamei T, et al. Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology. Cancer Cytopathol. 2013;121:415–22.

    Article  PubMed  Google Scholar 

  8. Onofre FB, Onofre AS, Pomjanski N, et al. 9 p21 deletion in the diagnosis of malignant mesothelioma in serous effusions additional to immunocytochemistry, DNA-ICM, and AgNOR analysis. Cancer. 2008;114:204–15.

    Article  PubMed  Google Scholar 

  9. Hida T, Matsumoto S, Hamasaki M, et al. Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue. Cancer Sci. 2015;106:1635–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hwang HC, Sheffield BS, Rodriguez S, et al. Utility of BAP1 immunohistochemistry and p16 (CDKN2A) FISH in the diagnosis of malignant mesothelioma in effusion cytology specimens. Am J Surg Pathol. 2016;40:120–6.

    Article  PubMed  Google Scholar 

  11. Walts AE, Hiroshima K, McGregor SM, et al. BAP1 immunostain and CDKN2A (p16) FISH analysis: clinical applicability for the diagnosis of malignant mesothelioma in effusions. Diagn Cytopathol. 2016;44:599–606.

    Article  PubMed  Google Scholar 

  12. Flores-Staino C, Darai-Ramqvist E, Dobra K, et al. Adaptation of a commercial fluorescent in situ hybridization test to the diagnosis of malignant cells in effusions. Lung Cancer. 2010;68:39–43.

    Article  PubMed  Google Scholar 

  13. Savic S, Franco N, Grilli B, et al. Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology. Chest. 2010;138:137–44.

    Article  CAS  PubMed  Google Scholar 

  14. Shin HJ, Shin DM, Tarco E, et al. Detection of numerical aberrations of chromosomes 7 and 9 in cytologic specimens of pleural malignant mesothelioma. Cancer. 2003;99:233–9.

    Article  PubMed  Google Scholar 

  15. O’Connell JT, Hacker CM, Barsky SH. MUC2 is a molecular marker for pseudomyxoma peritonei. Mod Pathol. 2002;15:958–72.

    Article  PubMed  Google Scholar 

  16. Li X, Wan L, Shen H, et al. Thyroid transcription factor-1 amplification and expressions in lung adenocarcinoma tissues and pleural effusions predict patient survival and prognosis. J Thorac Oncol. 2012;7:76–84.

    Article  CAS  PubMed  Google Scholar 

  17. Yu CJ, Shew JY, Liaw YS, et al. Application of mucin quantitative competitive reverse transcription polymerase chain reaction in assisting the diagnosis of malignant pleural effusion. Am J Respir Crit Care Med. 2001;164:1312–8.

    Article  CAS  PubMed  Google Scholar 

  18. Sakaguchi M, Virmani AK, Ashfaq R, et al. Development of a sensitive, specific reverse transcriptase polymerase chain reaction-based assay for epithelial tumour cells in effusions. Br J Cancer. 1999;79:416–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hofmann M, Ruschenburg I. mRNA detection of tumor-rejection genes BAGE, GAGE, and MAGE in peritoneal fluid from patients with ovarian carcinoma as a potential diagnostic tool. Cancer. 2002;96:187–93.

    Article  CAS  PubMed  Google Scholar 

  20. Saito T, Kobayashi M, Harada R, et al. Sensitive detection of small cell lung carcinoma cells by reverse transcriptase-polymerase chain reaction for prepro-gastrin-releasing peptide mRNA. Cancer. 2003;97:2504–11.

    Article  CAS  PubMed  Google Scholar 

  21. Fiegl M, Haun M, Massoner A, et al. Combination of cytology, fluorescence in situ hybridization for aneuploidy, and reverse-transcriptase polymerase chain reaction for human mammaglobin/mammaglobin B expression improves diagnosis of malignant effusions. J Clin Oncol. 2004;22:474–83.

    Article  CAS  PubMed  Google Scholar 

  22. Mohamed F, Vincent N, Cottier M, et al. Improvement of malignant serous effusions diagnosis by quantitative analysis of molecular claudin 4 expression. Biomarkers. 2010;15:315–24.

    Article  CAS  PubMed  Google Scholar 

  23. Salani R, Davidson B, Fiegl M, et al. Measurement of cyclin E genomic copy number and strand length in cell-free DNA distinguish malignant versus benign effusions. Clin Cancer Res. 2007;13:5805–9.

    Article  CAS  PubMed  Google Scholar 

  24. Wang T, Qian X, Wang Z, et al. Detection of cell-free BIRC5 mRNA in effusions and its potential diagnostic value for differentiating malignant and benign effusions. Int J Cancer. 2009;125:1921–5.

    Article  CAS  PubMed  Google Scholar 

  25. Tiwari SR, Mishra P, Abraham J. Neratinib, a novel HER2-targeted tyrosine kinase inhibitor. Clin Breast Cancer. 2016;16:344–8.

    Article  CAS  PubMed  Google Scholar 

  26. Lordick F, Janjigian YY. Clinical impact of tumour biology in the management of gastroesophageal cancer. Nat Rev Clin Oncol. 2016;13:348–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Graham DM, Coyle VM, Kennedy RD, et al. Molecular subtypes and personalized therapy in metastatic colorectal cancer. Curr Colorectal Cancer Rep. 2016;12:141–50.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yeung C, Hilton J, Clemons M, et al. Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours-a review. Cancer Metastasis Rev. 2016;35:427–37.

    Article  CAS  PubMed  Google Scholar 

  29. Shabaik A, Lin G, Peterson M, et al. Reliability of Her2/neu, estrogen receptor, and progesterone receptor testing by immunohistochemistry on cell block of FNA and serous effusions from patients with primary and metastatic breast carcinoma. Diagn Cytopathol. 2011;39:328–32.

    Article  PubMed  Google Scholar 

  30. Schlüter B, Gerhards R, Strumberg D, et al. Combined detection of Her2/neu gene amplification and protein overexpression in effusions from patients with breast and ovarian cancer. J Cancer Res Clin Oncol. 2010;136:1389–400.

    Article  CAS  PubMed  Google Scholar 

  31. Arihiro K, Oda M, Ogawa K, et al. Discordant HER2 status between primary breast carcinoma and recurrent/metastatic tumors using fluorescence in situ hybridization on cytological samples. Jpn J Clin Oncol. 2013;43:55–62.

    Article  PubMed  Google Scholar 

  32. Nakayama Y, Nakagomi H, Omori M, et al. Benefits of using the cell block method to determine the discordance of the HR/HER2 expression in patients with metastatic breast cancer. Breast Cancer. 2016;23:633–9.

    Article  PubMed  Google Scholar 

  33. Bozzetti C, Negri FV, Lagrasta CA, et al. Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer. 2011;104:1372–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sheikine Y, Rangachari D, McDonald DC, et al. EGFR testing in advanced non-small-cell lung cancer, a mini-review. Clin Lung Cancer. 2016;17:483–92.

    Article  CAS  PubMed  Google Scholar 

  35. Ellison G, Zhu G, Moulis A, et al. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol. 2013;66:79–89.

    Article  CAS  PubMed  Google Scholar 

  36. Goto K, Satouchi M, Ishii G, et al. An evaluation study of EGFR mutation tests utilized for non-small-cell lung cancer in the diagnostic setting. Ann Oncol. 2012;23:2914–9.

    Article  CAS  PubMed  Google Scholar 

  37. Sun PL, Jin Y, Kim H, et al. High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas. Cancer Cytopathol. 2013;121:311–9.

    Article  CAS  PubMed  Google Scholar 

  38. Yeo CD, Kim JW, Kim KH, et al. Detection and comparison of EGFR mutations in matched tumor tissues, cell blocks, pleural effusions, and sera from patients with NSCLC with malignant pleural effusion, by PNA clamping and direct sequencing. Lung Cancer. 2013;81:207–12.

    Article  PubMed  Google Scholar 

  39. Kang JY, Park CK, Yeo CD, et al. Comparison of PNA clamping and direct sequencing for detecting KRAS mutations in matched tumour tissue, cell block, pleural effusion and serum from patients with malignant pleural effusion. Respirology. 2015;20:138–46.

    Article  PubMed  Google Scholar 

  40. Buttitta F, Felicioni L, Del Grammastro M, et al. Effective assessment of egfr mutation status in bronchoalveolar lavage and pleural fluids by next-generation sequencing. Clin Cancer Res. 2013;19:691–8.

    Article  CAS  PubMed  Google Scholar 

  41. Facchinetti F, Tiseo M, Di Maio M, et al. Tackling ALK in non-small cell lung cancer: the role of novel inhibitors. Transl Lung Cancer Res. 2016;5:301–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Soda M, Isobe K, Inoue A, North-East Japan Study Group, ALK Lung Cancer Study Group, et al. A prospective PCR-based screening for the EML4-ALK oncogene in non-small cell lung cancer. Clin Cancer Res. 2012;18:5682–9.

    Article  CAS  PubMed  Google Scholar 

  43. Wu SG, Kuo YW, Chang YL, et al. EML4-ALK translocation predicts better outcome in lung adenocarcinoma patients with wild-type EGFR. J Thorac Oncol. 2012;7:98–104.

    Article  CAS  PubMed  Google Scholar 

  44. Chen YL, Lee CT, Lu CC, et al. Epidermal growth factor receptor mutation and anaplastic lymphoma kinase gene fusion: detection in malignant pleural effusion by RNA or PNA analysis. PLoS One. 2016;11:e0158125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Saito M, Shiraishi K, Kunitoh H, et al. Gene aberrations for precision medicine against lung adenocarcinoma. Cancer Sci. 2016;107:713–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tsai TH, Wu SG, Hsieh MS. Clinical and prognostic implications of RET rearrangements in metastatic lung adenocarcinoma patients with malignant pleural effusion. Lung Cancer. 2015;88:208–14.

    Article  PubMed  Google Scholar 

  47. Akamatsu H, Koh Y, Kenmotsu H, et al. Multiplexed molecular profiling of lung cancer using pleural effusion. J Thorac Oncol. 2014;9:1048–52.

    Article  CAS  PubMed  Google Scholar 

  48. Roscilli G, De Vitis C, Ferrara FF, et al. Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity. J Transl Med. 2016;14:61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Puglisi M, Stewart A, Thavasu P, et al. Characterisation of the phosphatidylinositol 3-kinase pathway in non-small cell lung cancer cells isolated from pleural effusions. Oncology. 2016;90:280–8.

    Article  CAS  PubMed  Google Scholar 

  50. DiBardino DM, Saqi A, Elvin JA, et al. Yield and clinical utility of next-generation sequencing in selected patients with lung adenocarcinoma. Clin Lung Cancer. 2016;17:517–522.e3.

    Article  CAS  PubMed  Google Scholar 

  51. Wei S, Lieberman D, Morrissette JJ, et al. Using “residual” FNA rinse and body fluid specimens for next-generation sequencing: an institutional experience. Cancer Cytopathol. 2016;124:324–9.

    Article  CAS  PubMed  Google Scholar 

  52. Lim B, Kim C, Kim JH, et al. Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites. Oncotarget. 2016;7:8055–66.

    PubMed  PubMed Central  Google Scholar 

  53. Castellarin M, Milne K, Zeng T, et al. Clonal evolution of high-grade serous ovarian carcinoma from primary to recurrent disease. J Pathol. 2013;229:515–24.

    Article  CAS  PubMed  Google Scholar 

  54. Shah RH, Scott SN, Brannon AR, et al. Comprehensive mutation profiling by next-generation sequencing of effusion fluids from patients with high-grade serous ovarian carcinoma. Cancer Cytopathol. 2015;123:289–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Reinartz S, Finkernagel F, Adhikary T, et al. A transcriptome-based global map of signaling pathways in the ovarian cancer microenvironment associated with clinical outcome. Genome Biol. 2016;17:108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Davidson, B. (2018). Molecular Cytology of Serous Effusions. In: Schmitt, F. (eds) Molecular Applications in Cytology. Springer, Cham. https://doi.org/10.1007/978-3-319-74942-6_6

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  • DOI: https://doi.org/10.1007/978-3-319-74942-6_6

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