Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers

Abstract

Objective-The Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC).Methods-Women were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel+carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide+cisplatin vs. paclitaxel+cisplatin in suboptimally-resected, advanced stage EOC. The N-terminal DO-7 p53 antibody was used to examine the expression of the major normal and mutant p53-isoforms. p53 overexpression was defined as ≥10% tumor cells exhibiting nuclear staining. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-p53 overexpression assessed by DO-7 immunostaining is common in early and advanced stage EOC, but has limited prognostic value in women treated with surgical staging and platinum-based combination chemotherapy. NIH Public Access

The apoptosis regulators p53, bax and PUMA: Relationship and impact on outcome in early stage (FIGO I-II) ovarian carcinoma after post-surgical taxane-based treatmen

“…Patients with p53-positive tumors continued to die of disease after the 5-year checkpoint and survival at 100 months from diagnosis was only 43%. The risk of late recurrent disease for patients with p53 overexpression of tumors also was noted in the GOG-157 study (23). A strong correlation has been observed between a p53 mutation and DO-7 expression of the p53 protein, the antibody used in the present study (23,24).…”

Qualitative Age Interactions between Low-grade and High-grade Serous Ovarian Carcinomas

“…Indeed, contemporary molecular-based models implicate two major carcinogenic pathways (2,(6)(7)(8). High-grade SOCs represent the majority of invasive ovarian cancers (9)(10)(11), and typically show molecular signatures or DNA amplification associated with genetic instability (12)(13)(14)(15)(16). Low-grade SOCs, which can also spread progressively (17,18), have been associated with stable oncogenic mutations (KRAS or BRAF) that influence cell proliferation (2,19).…”

“…There is growing interest in defining the molecular determinants of ovarian cancer risk, including cancer genomic patterns, epigenetic modifications, and molecular signatures (3,13,15,16,(20)(21)(22)(23). Although a major gradebased dichotomy in SOC molecular biology is now widely acknowledged, the age-specific risks relevant to heterogeneity in the carcinogenic pathways have not been fully explored.…”

Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis

“…[18][19][20] In view of these different patterns of immunoexpression associated with mutant TP53, it is therefore not surprising that studies correlating TP53 gene status and/or p53 overexpression with clinical outcome and response to chemotherapy in ovarian/pelvic serous carcinoma have reported conflicting results. 10,12,19,[21][22][23][24][25][26][27] Some of the studies that focused on ovarian high-grade serous carcinomas failed to demonstrate correlation between TP53 mutation and survival that to some extent have been related to the fact that TP53 mutation is an early event in high-grade serous carcinogenesis with near ubiquitous occurrence. 21,25,28,29 In addition, accurate pathological classification of ovarian carcinoma is frequently lacking in many reports as evidenced by the use of the all encompassing diagnosis 'ovarian cancer', without segregating tumors by histological type.…”

“…Some studies have simply used a cuff-off of as little as 10% of positive cells staining, whereas other have employed complicated scoring systems, which take into account both the quantity of positive cells, as well as the staining intensity. 22,25,27,30,31 In addition to the lack of uniform scoring systems, variations in immunohistochemical protocols make data from different studies difficult to compare and interpret. The aim of this study was to correlate immunohistochemical staining patterns of p53 expression in ovarian carcinomas with mutational analysis in order to establish practical immunohistochemical cut-points, which can be used to infer the presence of a TP53 mutation.…”