p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
Details
Publication Year 2023-05,Volume 9,Issue #3,Page 208-222
Journal Title
Journal of Pathology: Clinical Research
Publication Type
Research article
Abstract
Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
Publisher
Wiley
Keywords
Humans; Female; Tumor Suppressor Protein p53/genetics/metabolism; *Ovarian Neoplasms/pathology; Carcinoma, Ovarian Epithelial; *Carcinoma, Endometrioid/metabolism; Tp53; clear cell; endometrioid; high-grade serous carcinoma; ovarian cancer; p53; prognosis
Department(s)
Laboratory Research
PubMed ID
36948887
Open Access at Publisher's Site
https://doi.org/10.1002/cjp2.311
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2023-08-15 07:31:28
Last Modified: 2023-08-15 07:32:14

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