Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies

作者：Martin Köbel, Steve E. Kalloger, Niki Boyd, Steven E. McKinney, Erika Mehl, Chana Palmer, Samuel C. Y. Leung, Nathan J. Bowen, Diana N. Ionescu, Ashish B. Rajput, Leah Prentice, Dianne M. Miller, Jennifer L. Santos, Kenneth D. Swenerton, C. Blake Gilks, David George Huntsman · 发表于：PLoS Medicine · 年份：2008 · DOI：10.1371/journal.pmed.0050232 · 被引用次数：829 · 研究领域：Ovarian cancer diagnosis and treatment、Ferroptosis and cancer prognosis、Reproductive Biology and Fertility

BACKGROUND: Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous) are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. METHODS AND FINDINGS: In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1) in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognosti...