Abstract
Ovarian carcinoma is the leading cause of gynecological malignancy, with the serous subtype being the most commonly presented subtype. Recent studies have demonstrated that grade does not yield significant prognostic information, independent of TNM staging. As such, several different grading systems have been proposed to reveal morphological characteristics of these tumors, however each yield different results. To help address this issue, we performed a rigorous computational analysis to better understand the molecular differences that fundamentally explain the different grades and grading systems. mRNA abundance levels were analyzed across 334 total patients and their association with each grade and grading system were assessed. Few molecular differences were observed between grade 2 and 3 tumors when using the International Federation of Gynecology and Obstetrics (FIGO) grading system, suggesting their molecular similarity. In contrast, grading by the Silverberg system reveals that grades 1–3 are molecularly equidistant from one another across a spectrum. Additionally, we have identified a few candidate genes with good prognostic information that could potentially be used for classifying cases with similar morphological appearances.
Highlights
Ovarian cancer is one of the most lethal gynecological cancers and is the fifth most common cause of cancer death in North America [1]
Cancer Medicine published by John Wiley & Sons Ltd
The large The Cancer Genome Atlas (TCGA) dataset [18] was not included in this study as it did not annotate which grading system was used, and the project spanned several years of reporting, it was likely that both grading systems were used at some centers
Summary
Ovarian cancer is one of the most lethal gynecological cancers and is the fifth most common cause of cancer death in North America [1]. Many subtypes of epithelial ovarian carcinoma exist including the serous, clear cell, endometrioid, and mucinous subtypes [2]. Histopathological grade is intended to provide additional information to a nominal diagnostic category; information which should have prognostic or therapeutic implications. Each grading systems employs a different scheme, but most are ternary systems stratifying ovarian serous carcinomas into well, moderately, and poorly differentiated categories. These ternary grading systems imply a progressive deterioration in differentiation, and the Silverberg, FIGO, and WHO systems are a 2014 The Authors.
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