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Construction and Analysis of Multiparameter Prognostic Models for Melanoma Outcome

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Molecular Diagnostics for Melanoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1102))

Abstract

The outcome of Stage II melanoma is uncertain. Despite that 10-year melanoma-specific survival can approach 50 % following curative-intent wide local excision and negative sentinel lymph node biopsy, the adverse risk–benefit ratio of interferon-based adjuvant regimens precludes their use in most patients. The discovery and translation of protein-based prognostic biomarkers into the clinic offers the promise for residual risk stratification of Stage II melanoma patients beyond conventional clinicopathologic criteria to identify an additional subset of patients who, based upon tumor molecular profiles, might also derive benefit from adjuvant regimens. Despite incorporation of Ki-67 assays into clinical practice, systematic review of REMARK-compliant, immunostain-based prognostic biomarker assays in melanoma suggests that residual risk of recurrence might be best explained by a composite score derived from a small panel of proteins representing independent features of melanoma biology. Reflecting this trend, to date, five such multiparameter melanoma prognostic models have been published. Here, we review these five models and provide detailed protocols for discovering and validating multiparameter models including: appropriate cohort recruitment strategies, comprehensive laboratory protocols supporting fully quantitative chromogenic or fluorescent immunostaining platforms, statistical approaches to create composite prognostic indices recommended steps for model validation in independent cohorts.

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References

  1. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, CoitDG DS, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27(36):6199–6206

    Article  PubMed  Google Scholar 

  2. Petrella T, Verma S, Spithoff K, Quirt I, McCready D (2012) Adjuvant interferon therapy for patients at high risk for recurrent melanoma: an updated systematic review and practice guideline. Clin Oncol (R Coll Radiol) 24(6):413–423

    Article  CAS  Google Scholar 

  3. Thompson JF, Soong SJ, Balch CM, Gershenwald JE, Ding S, Coit DG, Flaherty KT, Gimotty PA, Johnson T, Johnson MM, Leong SP, Ross MI, Byrd DR, Cascinelli N, Cochran AJ, Eggermont AM, McMasters KM, Mihm MC Jr, Morton DL, Sondak VK (2011) Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol 29(16):2199–2205

    Article  PubMed  Google Scholar 

  4. Gould Rothberg BE, Bracken MB, Rimm DL (2009) Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst 101(7):452–474

    Article  PubMed  Google Scholar 

  5. Altman DG, McShane LM, Sauerbrei W, Taube SE (2012) Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. PLoS Med 9(5):e1001216, PMEDICINE-D-11-01220 [pii]

    Article  PubMed  Google Scholar 

  6. Schramm SJ, Mann GJ (2011) Melanoma prognosis: a REMARK-based systematic review and bioinformatic analysis of immunohistochemical and gene microarray studies. Mol Cancer Ther 10(8):1520–1528

    Article  CAS  PubMed  Google Scholar 

  7. Meyer S, Fuchs TJ, Bosserhoff AK, Hofstadter F, Pauer A, Roth V, Buhmann JM, Moll I, Anagnostou N, Brandner JM, Ikenberg K, Moch H, Landthaler M, Vogt T, Wild PJ (2012) A seven-marker signature and clinical outcome in malignant melanoma: a large-scale tissue-microarray study with two independent patient cohorts. PLoS One 7(6):e38222. doi:10.1371/journal.pone.0038222

    Article  CAS  PubMed  Google Scholar 

  8. Vaisanen A, Kuvaja P, Kallioinen M, Turpeenniemi-Hujanen T (2011) A prognostic index in skin melanoma through the combination of matrix metalloproteinase-2, Ki67, and p53. Hum Pathol 42(8):1103–1111

    Article  PubMed  Google Scholar 

  9. Nodin B, Fridberg M, Jonsson L, Bergman J, Uhlen M, Jirstrom K (2012) High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma. Diagn Pathol 7:82. doi:1746-1596-7-82 [pii]

    Article  CAS  PubMed  Google Scholar 

  10. Ladstein RG, Bachmann IM, Straume O, Akslen LA (2010) Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma. BMC Cancer 10:140. doi:10.1186/1471-2407-10-140

    Article  PubMed  Google Scholar 

  11. Ladstein RG, Bachmann IM, Straume O, Akslen LA (2012) Prognostic importance of the mitotic marker phosphohistone H3 in cutaneous nodular melanoma. J Invest Dermatol 132(4):1247–1252. doi:10.1038/jid.2011.464, jid2011464 [pii]

    Article  CAS  PubMed  Google Scholar 

  12. Jonsson L, Bergman J, Nodin B, Manjer J, Ponten F, Uhlen M, Jirstrom K (2011) Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmo Diet and Cancer Study. J Transl Med 9:114. doi:10.1186/1479-5876-9-114, 1479-5876-9-114 [pii]

    Article  PubMed  Google Scholar 

  13. Gremel G, Ryan D, Rafferty M, Lanigan F, Hegarty S, Lavelle M, Murphy I, Unwin L, Joyce C, Faller W, McDermott EW, Sheahan K, Ponten F, Gallagher WM (2011) Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma. Br J Cancer 105(4):565–574. doi:10.1038/bjc.2011.249, bjc2011249 [pii]

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Z, Chen G, Cheng Y, Martinka M, Li G (2011) Prognostic significance of RUNX3 expression in human melanoma. Cancer 117(12):2719–2727. doi:10.1002/cncr.25838

    Article  CAS  PubMed  Google Scholar 

  15. Chen G, Cheng Y, Zhang Z, Martinka M, Li G (2011) Cytoplasmic Skp2 expression is increased in human melanoma and correlated with patient survival. PLoS One 6(2):e17578. doi:10.1371/journal.pone.0017578

    Article  CAS  PubMed  Google Scholar 

  16. Svobodova S, Browning J, MacGregor D, Pollara G, Scolyer RA, Murali R, Thompson JF, Deb S, Azad A, Davis ID, Cebon JS (2011) Cancer-testis antigen expression in primary cutaneous melanoma has independent prognostic value comparable to that of Breslow thickness, ulceration and mitotic rate. Eur J Cancer 47(3):460–469. doi:10.1016/j.ejca.2010.09.042, S0959-8049(10)00963-9 [pii]

    Article  CAS  PubMed  Google Scholar 

  17. Jafarnejad SM, Wani AA, Martinka M, Li G (2010) Prognostic significance of Sox4 expression in human cutaneous melanoma and its role in cell migration and invasion. Am J Pathol 177(6):2741–2752. doi:10.2353/ajpath.2010.100377, S0002-9440(10)62903-3 [pii]

    Article  CAS  PubMed  Google Scholar 

  18. Li J, Cheng Y, Tai D, Martinka M, Welch DR, Li G (2011) Prognostic significance of BRMS1 expression in human melanoma and its role in tumor angiogenesis. Oncogene 30(8):896–906. doi:10.1038/onc.2010.470, onc2010470 [pii]

    Article  PubMed  Google Scholar 

  19. Rotte A, Martinka M, Li G (2012) MMP2 expression is a prognostic marker for primary melanoma patients. Cell Oncol (Dordr) 35(3):207–216. doi:10.1007/s13402-012-0080-x

    Article  CAS  Google Scholar 

  20. Brown ER, Doig T, Anderson N, Brenn T, Doherty V, Xu Y, Bartlett JM, Smyth JF, Melton DW (2012) Association of galectin-3 expression with melanoma progression and prognosis. Eur J Cancer 48(6):865–874. doi:10.1016/j.ejca.2011.09.003, S0959-8049(11)00714-3 [pii]

    Article  CAS  PubMed  Google Scholar 

  21. Buljan M, Situm M, Tomas D, Milosevic M, Kruslin B (2011) Prognostic value of galectin-3 in primary cutaneous melanoma. J Eur Acad Dermatol Venereol 25(10):1174–1181. doi:10.1111/j.1468-3083.2010.03943.x

    Article  CAS  PubMed  Google Scholar 

  22. Pencina MJ, D’Agostino RB, Pencina KM, Janssens AC, Greenland P (2012) Interpreting incremental value of markers added to risk prediction models. Am J Epidemiol 176(6):473–481. doi:10.1093/aje/kws207, kws207 [pii]

    Article  PubMed  Google Scholar 

  23. Weinlich G, Eisendle K, Hassler E, Baltaci M, Fritsch PO, Zelger B (2006) Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients. Br J Cancer 94(6):835–841

    Article  CAS  PubMed  Google Scholar 

  24. Weinlich G, Topar G, Eisendle K, Fritsch PO, Zelger B (2007) Comparison of metallothionein-overexpression with sentinel lymph node biopsy as prognostic factors in melanoma. J Eur Acad Dermatol Venereol 21(5):669–677

    CAS  PubMed  Google Scholar 

  25. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826

    Article  CAS  PubMed  Google Scholar 

  26. Cronin M, Sangli C, Liu ML, Pho M, Dutta D, Nguyen A, Jeong J, Wu J, Langone KC, Watson D (2007) Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer. Clin Chem 53(6):1084–1091. doi:10.1373/clinchem.2006.076497, clinchem.2006.076497 [pii]

    Article  CAS  PubMed  Google Scholar 

  27. Buyse M, Loi S, Van’t Veer L, Viale G, Delorenzi M, Glas AM, d’ Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98(17):1183–1192. doi:10.1093/jnci/djj329, 98/17/1183 [pii]

    Article  CAS  PubMed  Google Scholar 

  28. Glas AM, Floore A, Delahaye LJ, Witteveen AT, Pover RC, Bakx N, Lahti-Domenici JS, Bruinsma TJ, Warmoes MO, Bernards R, Wessels LF, Van;t Veer LJ (2006) Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics 7:278. doi:10.1186/1471-2164-7-278, 1471-2164-7-278 [pii]

    Article  PubMed  Google Scholar 

  29. Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, Beaumont C, Clark-Langone KM, Yoshizawa CN, Lee M, Watson D, Shak S, Kerr DJ (2011) Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol 29(35):4611–4619. doi:10.1200/JCO.2010.32.8732, JCO.2010.32.8732 [pii]

    Article  PubMed  Google Scholar 

  30. Salazar R, Roepman P, Capella G, Moreno V, Simon I, Dreezen C, Lopez-Doriga A, Santos C, Marijnen C, Westerga J, Bruin S, Kerr D, Kuppen P, van de Velde C, Morreau H, Van Velthuysen L, Glas AM, Van’t Veer LJ, Tollenaar R (2011) Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J Clin Oncol 29(1):17–24. doi:10.1200/JCO.2010.30.1077, JCO.2010.30.1077 [pii]

    Article  PubMed  Google Scholar 

  31. Bartlett JM, Bloom KJ, Piper T, Lawton TJ, van de Velde CJ, Ross DT, Ring BZ, Seitz RS, Beck RA, Hasenburg A, Kieback D, Putter H, Markopoulos C, Dirix L, Seynaeve C, Rea D (2012) Mammostrat as an immunohistochemical multigene assay for prediction of early relapse risk in the tamoxifen versus exemestane adjuvant multicenter trial pathology study. J Clin Oncol. doi:10.1200/JCO.2012.42.8896, JCO.2012.42.8896 [pii]

    Google Scholar 

  32. Gould Rothberg BE, Berger AJ, Molinaro AM, Subtil A, Krauthammer MO, Camp RL, Bradley WR, Ariyan S, Kluger HM, Rimm DL (2009) A melanoma prognostic model using tissue microarrays and genetic algorithms. J Clin Oncol 27(34):5772–5780

    Article  PubMed  Google Scholar 

  33. Kashani-Sabet M, Venna S, Nosrati M, Rangel J, Sucker A, Egberts F, Baehner FL, Simko J, Leong SP, Haqq C, Hauschild A, Schadendorf D, Miller JR 3rd, Sagebiel RW (2009) A multimarker prognostic assay for primary cutaneous melanoma. Clin Cancer Res 15(22):6987–6992. doi:10.1158/1078-0432.CCR-09-1777, 1078-0432.CCR-09-1777 [pii]

    Article  CAS  PubMed  Google Scholar 

  34. Piras F, Perra MT, Murtas D, Minerba L, Floris C, Maxia C, Demurtas P, Ugalde J, Ribatti D, Sirigu P (2008) Combinations of apoptosis and cell-cycle control biomarkers predict the outcome of human melanoma. Oncol Rep 20(2):271–277

    PubMed  Google Scholar 

  35. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4(7):844–847

    Article  CAS  PubMed  Google Scholar 

  36. Moeder CB, Giltnane JM, Moulis SP, Rimm DL (2009) Quantitative, fluorescence-based in-situ assessment of protein expression. Methods Mol Biol 520:163–175

    Article  CAS  PubMed  Google Scholar 

  37. Rimm DL, Camp RL, Charette LA, Olsen DA, Provost E (2001) Amplification of tissue by construction of tissue microarrays. Exp Mol Pathol 70(3):255–264

    Article  CAS  PubMed  Google Scholar 

  38. DiVito KA, Charette LA, Rimm DL, Camp RL (2004) Long-term preservation of antigenicity on tissue microarrays. Lab Invest 84(8):1071–1078

    Article  CAS  PubMed  Google Scholar 

  39. Brennan DJ, Rexhepaj E, O’Brien SL, McSherry E, O’Connor DP, Fagan A, Culhane AC, Higgins DG, Jirstrom K, Millikan RC, Landberg G, Duffy MJ, Hewitt SM, Gallagher WM (2008) Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer. Clin Cancer Res 14(9):2681–2689. doi:10.1158/1078-0432.CCR-07-1760, 14/9/2681 [pii]

    Article  CAS  PubMed  Google Scholar 

  40. Rexhepaj E, Brennan DJ, Holloway P, Kay EW, McCann AH, Landberg G, Duffy MJ, Jirstrom K, Gallagher WM (2008) Novel image analysis approach for quantifying expression of nuclear proteins assessed by immunohistochemistry: application to measurement of oestrogen and progesterone receptor levels in breast cancer. Breast Cancer Res 10(5):R89. doi:10.1186/bcr2187, bcr2187 [pii]

    Article  PubMed  Google Scholar 

  41. Lloyd MC, Allam-Nandyala P, Purohit CN, Burke N, Coppola D, Bui MM (2010) Using image analysis as a tool for assessment of prognostic and predictive biomarkers for breast cancer: how reliable is it? J Pathol Inform 1:29. doi:10.4103/2153-3539.74186

    Article  PubMed  Google Scholar 

  42. Camp RL, Chung GG, Rimm DL (2002) Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med 8(11):1323–1327

    Article  CAS  PubMed  Google Scholar 

  43. Neumeister V, Agarwal S, Bordeaux J, Camp RL, Rimm DL (2010) In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosis. Am J Pathol 176(5):2131–2138. doi:10.2353/ajpath.2010.090712, S0002-9440(10)60010-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  44. Goens G, Rusu D, Bultot L, Goval JJ, Magdalena J (2009) Characterization and quality control of antibodies used in ChIP assays. Methods Mol Biol 567:27–43. doi:10.1007/978-1-60327-414-2_2

    Article  CAS  PubMed  Google Scholar 

  45. Larsson PH (2008) Purification of antibodies. Methods Mol Med 138:197–207. doi:10.1007/978-1-59745-366-0_16

    Article  CAS  PubMed  Google Scholar 

  46. Bordeaux J, Welsh A, Agarwal S, Killiam E, Baquero M, Hanna J, Anagnostou V, Rimm D (2010) Antibody validation. Biotechniques 48(3):197–209. doi:10.2144/000113382, 000113382 [pii]

    Article  CAS  PubMed  Google Scholar 

  47. Welsh AW, Moeder CB, Kumar S, Gershkovich P, Alarid ET, Harigopal M, Haffty BG, Rimm DL (2011) Standardization of estrogen receptor measurement in breast cancer suggests false-negative results are a function of threshold intensity rather than percentage of positive cells. J Clin Oncol 29(22):2978–2984. doi:10.1200/JCO.2010.32.9706, JCO.2010.32.9706 [pii]

    Article  CAS  PubMed  Google Scholar 

  48. Gustavson M, Dolled-Filhart M, Christiansen J, Pinard R, Rimm D (2009) AQUA technology and molecular pathology. In: Platero JS (ed) Molecular pathology in drug discovery and development. Wiley, Hoboken, NJ, pp 295–333

    Chapter  Google Scholar 

  49. Gustavson MD, Bourke-Martin B, Reilly DM, Cregger M, Williams C, Tedeschi G, Pinard R, Christiansen J (2009) Development of an unsupervised pixel-based clustering algorithm for compartmentalization of immunohistochemical expression using Automated QUantitative Analysis. Appl Immunohistochem Mol Morphol 17(4):329–337. doi:10.1097/PAI.0b013e318195ecaa

    Article  PubMed  Google Scholar 

  50. Gustavson MD, Molinaro AM, Tedeschi G, Camp RL, Rimm DL (2008) AQUA analysis of thymidylate synthase reveals localization to be a key prognostic biomarker in 2 large cohorts of colorectal carcinoma. Arch Pathol Lab Med 132(11):1746–1752. doi:10.1043/1543-2165-132.11.1746, 2007-0718-OA [pii]

    PubMed  Google Scholar 

  51. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57(1):289–300

    Google Scholar 

  52. Ooi CH, Tan P (2003) Genetic algorithms applied to multi-class prediction for the analysis of gene expression data. Bioinformatics 19(1):37–44

    Article  CAS  PubMed  Google Scholar 

  53. Breiman L, Friedman JH, Olshen RA, Stone CJ (1984) Classification and regression trees. CRC Press, Boca Raton, FL

    Google Scholar 

  54. Molinaro AM, Dudoit S, van der Laan MJ (2004) Tree-based multivariate regression and density estimation with right-censored data. J Multivar Anal 90:154–177

    Article  Google Scholar 

  55. Segal MR, Bloch DA (1989) A comparison of estimated proportional hazards models and regression trees. Stat Med 8(5):539–550

    Article  CAS  PubMed  Google Scholar 

  56. Gimotty PA, Elder DE, Fraker DL, Botbyl J, Sellers K, Elenitsas R, Ming ME, Schuchter L, Spitz FR, Czerniecki BJ, Guerry D (2007) Identification of high-risk patients among those diagnosed with thin cutaneous melanomas. J Clin Oncol 25(9):1129–1134

    Article  PubMed  Google Scholar 

  57. Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF (2001) Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19(16):3635–3648

    CAS  PubMed  Google Scholar 

  58. Massi D, Franchi A, Borgognoni L, Paglierani M, Reali UM, Santucci M (2002) Tumor angiogenesis as a prognostic factor in thick cutaneous malignant melanoma. A quantitative morphologic analysis. Virchows Arch 440(1):22–28

    Article  CAS  PubMed  Google Scholar 

  59. de Giorgi V, Rossari S, Gori A, Grazzini M, Savarese I, Crocetti E, Cervadoro E, Massi D (2012) The prognostic impact of the anatomical sites in the ‘head and neck melanoma’: scalp versus face and neck. Melanoma Res 22(5):402–405. doi:10.1097/CMR.0b013e3283577b96

    Article  PubMed  Google Scholar 

  60. Thies A, Mangold U, Moll I, Schumacher U (2001) PAS-positive loops and networks as a prognostic indicator in cutaneous malignant melanoma. J Pathol 195(5):537–542. doi:10.1002/path.988, 10.1002/path.988 [pii]

    Article  CAS  PubMed  Google Scholar 

  61. Gimotty PA, Guerry D (2010) Prognostication in thin cutaneous melanomas. Arch Pathol Lab Med 134(12):1758–1763. doi:10.1043/2009-0653-RAR.1, 10.1043/2009-0653-RAR.1 [pii]

    PubMed  Google Scholar 

  62. Lindholm C, Andersson R, Dufmats M, Hansson J, Ingvar C, Moller T, Sjodin H, Stierner U, Wagenius G (2004) Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors. Cancer 101(9):2067–2078. doi:10.1002/cncr.20602

    Article  PubMed  Google Scholar 

  63. Storr SJ, Safuan S, Mitra A, Elliott F, Walker C, Vasko MJ, Ho B, Cook M, Mohammed RA, Patel PM, Ellis IO, Newton-Bishop JA, Martin SG (2012) Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma. Mod Pathol 25(4):493–504. doi:10.1038/modpathol.2011.182, modpathol2011182 [pii]

    Article  PubMed  Google Scholar 

  64. Xu X, Chen L, Guerry D, Dawson PR, Hwang WT, VanBelle P, Elder DE, Zhang PJ, Ming ME, Schuchter L, Gimotty PA (2012) Lymphatic invasion is independently prognostic of metastasis in primary cutaneous melanoma. Clin Cancer Res 18(1):229–237. doi:10.1158/1078-0432.CCR-11-0490, 1078-0432.CCR-11-0490 [pii]

    Article  PubMed  Google Scholar 

  65. Yun SJ, Gimotty PA, Hwang WT, Dawson P, Van Belle P, Elder DE, Elenitsas R, Schuchter L, Zhang PJ, Guerry D, Xu X (2011) High lymphatic vessel density and lymphatic invasion underlie the adverse prognostic effect of radial growth phase regression in melanoma. Am J Surg Pathol 35(2):235–242. doi:10.1097/PAS.0b013e3182036ccd, 00000478-201102000-00008 [pii]

    Article  PubMed  Google Scholar 

  66. Mills JL (1993) Data torturing. N Engl J Med 329(16):1196–1199

    Article  CAS  PubMed  Google Scholar 

  67. Molinaro AM, Simon R, Pfeiffer RM (2005) Prediction error estimation: a comparison of resampling methods. Bioinformatics 21(15):3301–3307

    Article  CAS  PubMed  Google Scholar 

  68. Deeks JJ, Altman DG, Bradburn MJ (2001) Chapter 15: Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: Egger M, Smith GD, Altman DG (eds) Systematic reviews in health care: meta-analysis in context, 2nd edn. BMJ Press, Cornwall, UK, pp 285–312

    Chapter  Google Scholar 

  69. Gould Rothberg BE, Bracken MB (2006) E-cadherin immunohistochemical expression as a prognostic factor in infiltrating ductal carcinoma of the breast: a systematic review and meta-analysis. Breast Cancer Res Treat 100(2):139–148. doi:10.1007/s10549-006-9248-2

    Article  CAS  PubMed  Google Scholar 

  70. Rothman KJ, Greenland S (2008) Chapter 7: Cohort studies. In: Rothman KJ, Greenland S, Lash TL (eds) Modern epidemiology, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, PA

    Google Scholar 

  71. Simon RM, Paik S, Hayes DF (2009) Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 101(21):1446–1452. doi:10.1093/jnci/djp335, djp335 [pii]

    Article  PubMed  Google Scholar 

  72. Tolles J, Bai Y, Baquero M, Harris LN, Rimm DL, Molinaro AM (2011) Optimal tumor sampling for immunostaining of biomarkers in breast carcinoma. Breast Cancer Res 13(3):R51. doi:10.1186/bcr2882, bcr2882 [pii]

    Article  PubMed  Google Scholar 

  73. Pacifico MD, Grover R, Richman P, Daley F, Wilson GD (2004) Validation of tissue microarray for the immunohistochemical profiling of melanoma. Melanoma Res 14(1):39–42, 00008390-200402000-00006 [pii]

    Article  PubMed  Google Scholar 

  74. Pacifico MD, Grover R, Richman PI, Buffa F, Daley FM, Wilson GD (2005) Identification of P-cadherin in primary melanoma using a tissue microarrayer: prognostic implications in a patient cohort with long-term follow up. Ann Plast Surg 55(3):316–320

    Article  CAS  PubMed  Google Scholar 

  75. Pearl RA, Pacifico MD, Richman PI, Wilson GD, Grover R (2008) Stratification of patients by melanoma cell adhesion molecule (MCAM) expression on the basis of risk: implications for sentinel lymph node biopsy. J Plast Reconstr Aesthet Surg 61:265–271

    Article  CAS  PubMed  Google Scholar 

  76. De Jong AS, Van Kessel-van VM, Raap AK (1985) Sensitivity of various visualization methods for peroxidase and alkaline phosphatase activity in immunoenzyme histochemistry. Histochem J 17(10):1119–1130

    Article  PubMed  Google Scholar 

  77. Harlow E, Lane D (2006) Detection of horseradish peroxidase-labeled reagents with aminoethylcarbazole. CSH Protoc 2006(1). doi:2006/1/pdb.prot4334 [pii]10.1101/pdb.prot4334

    Google Scholar 

  78. Altman DG, Lausen B, Sauerbrei W, Schumacher M (1994) Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst 86(11):829–835

    Article  CAS  PubMed  Google Scholar 

  79. Camp RL, Dolled-Filhart M, Rimm DL (2004) X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 10(21):7252–7259

    Article  CAS  PubMed  Google Scholar 

  80. Greenland S, Finkle WD (1995) A critical look at methods for handling missing covariates in epidemiologic regression analyses. Am J Epidemiol 142(12):1255–1264

    CAS  PubMed  Google Scholar 

  81. Ali AM, Dawson SJ, Blows FM, Provenzano E, Ellis IO, Baglietto L, Huntsman D, Caldas C, Pharoah PD (2011) Comparison of methods for handling missing data on immunohistochemical markers in survival analysis of breast cancer. Br J Cancer 104(4):693–699. doi:10.1038/sj.bjc.6606078, 6606078 [pii]

    Article  CAS  PubMed  Google Scholar 

  82. Emerson JW, Dolled-Filhart M, Harris L, Rimm DL, Tuck DP (2009) Quantitative assessment of tissue biomarkers and construction of a model to predict outcome in breast cancer using multiple imputation. Cancer Inform 7:29–40

    CAS  PubMed  Google Scholar 

  83. Alonso SR, Ortiz P, Pollan M, Perez-Gomez B, Sanchez L, Acuna MJ, Pajares R, Martinez-Tello FJ, Hortelano CM, Piris MA, Rodriguez-Peralto JL (2004) Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study. Am J Pathol 164(1):193–203

    Article  CAS  PubMed  Google Scholar 

  84. Vaisanen AH, Kallioinen M, Turpeenniemi-Hujanen T (2008) Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma. Hum Pathol 39:377–385

    Article  CAS  PubMed  Google Scholar 

  85. Pacifico MD, Grover R, Richman PI, Daley FM, Buffa F, Wilson GD (2005) Development of a tissue array for primary melanoma with long-term follow-up: discovering melanoma cell adhesion molecule as an important prognostic marker. Plast Reconstr Surg 115(2):367–375

    Article  CAS  PubMed  Google Scholar 

  86. Lin H, Wong RP, Martinka M, Li G (2009) Loss of SNF5 expression correlates with poor patient survival in melanoma. Clin Cancer Res 15(20):6404–6411. doi:10.1158/1078-0432.CCR-09-1135, 1078-0432.CCR-09-1135 [pii]

    Article  CAS  PubMed  Google Scholar 

  87. Ekmekcioglu S, Ellerhorst JA, Prieto VG, Johnson MM, Broemeling LD, Grimm EA (2006) Tumor iNOS predicts poor survival for stage III melanoma patients. Int J Cancer 119(4):861–866

    Article  CAS  PubMed  Google Scholar 

  88. Straume O, Sviland L, Akslen LA (2000) Loss of nuclear p16 protein expression correlates with increased tumor cell proliferation (Ki-67) and poor prognosis in patients with vertical growth phase melanoma. Clin Cancer Res 6(5):1845–1853

    CAS  PubMed  Google Scholar 

  89. Thies A, Moll I, Berger J, Wagener C, Brummer J, Schulze HJ, Brunner G, Schumacher U (2002) CEACAM1 expression in cutaneous malignant melanoma predicts the development of metastatic disease. J Clin Oncol 20(10):2530–2536

    Article  CAS  PubMed  Google Scholar 

  90. Florenes VA, Maelandsmo GM, Faye R, Nesland JM, Holm R (2001) Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome. J Pathol 195(5):530–536

    Article  CAS  PubMed  Google Scholar 

  91. Thies A, Schachner M, Moll I, Berger J, Schulze HJ, Brunner G, Schumacher U (2002) Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma. Eur J Cancer 38(13):1708–1716

    Article  CAS  PubMed  Google Scholar 

  92. Soltani MH, Pichardo R, Song Z, Sangha N, Camacho F, Satyamoorthy K, Sangueza OP, Setaluri V (2005) Microtubule-associated protein 2, a marker of neuronal differentiation, induces mitotic defects, inhibits growth of melanoma cells, and predicts metastatic potential of cutaneous melanoma. Am J Pathol 166(6):1841–1850

    Article  CAS  PubMed  Google Scholar 

  93. Niezabitowski A, Czajecki K, Rys J, Kruczak A, Gruchala A, Wasilewska A, Lackowska B, Sokolowski A, Szklarski W (1999) Prognostic evaluation of cutaneous malignant melanoma: a clinicopathologic and immunohistochemical study. J Surg Oncol 70(3):150–160

    Article  CAS  PubMed  Google Scholar 

  94. Piras F, Murtas D, Minerba L, Ugalde J, Floris C, Maxia C, Colombari R, Perra MT, Sirigu P (2007) Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanoma. Histopathology 50(7):835–842

    Article  CAS  PubMed  Google Scholar 

  95. Tran TA, Ross JS, Carlson JA, Mihm MC Jr (1998) Mitotic cyclins and cyclin-dependent kinases in melanocytic lesions. Hum Pathol 29(10):1085–1090

    Article  CAS  PubMed  Google Scholar 

  96. Florenes VA, Faye RS, Maelandsmo GM, Nesland JM, Holm R (2000) Levels of cyclin D1 and D3 in malignant melanoma: deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma. Clin Cancer Res 6(9):3614–3620

    CAS  PubMed  Google Scholar 

  97. McDermott NC, Milburn C, Curran B, Kay EW, Barry Walsh C, Leader MB (2000) Immunohistochemical expression of nm23 in primary invasive malignant melanoma is predictive of survival outcome. J Pathol 190(2):157–162

    Article  CAS  PubMed  Google Scholar 

  98. Pacifico MD, Grover R, Richman PI, Buffa F, Daley FM, Wilson GD (2005) nm23 as a prognostic marker in primary cutaneous melanoma: evaluation using tissue microarray in a patient group with long-term follow-up. Melanoma Res 15(5):435–440

    Article  CAS  PubMed  Google Scholar 

  99. Li Q, Murphy M, Ross J, Sheehan C, Carlson JA (2004) Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship. J Cutan Pathol 31(10):633–642

    Article  PubMed  Google Scholar 

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Rothberg, B.E.G., Rimm, D.L. (2014). Construction and Analysis of Multiparameter Prognostic Models for Melanoma Outcome. In: Thurin, M., Marincola, F. (eds) Molecular Diagnostics for Melanoma. Methods in Molecular Biology, vol 1102. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-727-3_13

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  • DOI: https://doi.org/10.1007/978-1-62703-727-3_13

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