Abstract 2045: Aneuploidy, immunohistochemical overexpression of MSH-2, P53, P21^WAF1/CIP1, P16^INK4A, and correlation to epithelial ovarian carcinoma patient prognosis
Authors: Kavitha Advikolanu Rao, Antony M. Magliocco, Andrew W. Maksymiuk
Journal: Cancer Research (2021)

Abstract Aneuploidy, immunohistochemical overexpression of MSH-2, P53, P21WAF1/CIP1, P16INK4A, and correlation to epithelial ovarian carcinoma patient prognosis Overexpression of MSH-2, P53, P21WAF1/CIP1, P16INK4A and DNA status in epithelial ovarian carcinoma (EOC) was determined in paraffin-embedded tissue (PET) to predict prognosis. Immunoreactivity, DNA and % S content were evaluated for their potential role in survival and relapse-free survival (RFS) in 112 patients diagnosed with EOC at Saskatoon Cancer Center, Canada. Immunostaining studies were with the following mouse monoclonal antibodies: MSH-2, FE11; P53, D07; P21WAF1/CIP1, EA 10; except for P16INK4A, rabbit, G175-405, 13251A. DNA and % S content (median, &amp;lt; % 5 = low-risk or &amp;gt; % 5 = high-risk) were assessed by flow-cytometric analysis1. Survival curves were determined by Kaplan-Meier method, mean survival time, and log rank test. P-values &amp;lt; 0.05 were considered significant; X2-test examined association between variables. Patients with aneuploid DNA had 59 months mean survival time, compared to cases with diploid DNA which had 89 months, (p = 0.03). RFS in those with diploid DNA lasted longer (84 months) while aneuploid cases had shorter time to progression (47 months, p = 0.01). % S content in the high-risk group, 47 cases, had worse survival (57 months, p = 0.0008) and RFS (52 months, p = 0.004). Aneuploidy was not related to overall survival within the subsets of early and advanced stage patients. Grade 2 patients with abnormal DNA and P53 expression were adversely associated with survival and RFS. Diploid DNA was observed in all mucinous tumors except in one case with aneuploid DNA. P53 immunoreactivity was related to shorter survival and RFS in 44 cases. P21WAF1/CIP1 overexpression was associated with P53 overexpression in 11 cases (p = 0.04) and shorter median survival (29 months) compared to negative P21WAF1/CIP1 staining (median survival time 62 months, p = 0.03). 11 grade 2 patients with P53 positivity had worse survival (59 months) and RFS (47 months) than the P53 negative tumors (p = 0.05, and p = 0.01 respectively). P16INK4A overexpression (46 cases) had no adverse effect on survival and RFS. No significant prognostic difference was found between MSH-2 positive and negative tumors. We conclude that % S content was a more beneficial prognostic marker than ploidy status. In grade 2 EOC, the effects of DNA content and P53 overexpression were significant variables related to outcome. For pathologists, these variables in grade 2 tumors can be adjunctive aid for reaching an agreement to diagnose the grade of EOC patients.Footnotes1 A. Geissel and J. L. Griffin, “Preparation of nuclei for flow cytometry,” in AFIP Advances in Laboratory Methods in histology and Pathology, ed. Mikel UV (Washington DC: American Registry of Pathology, 1944), 111-121. Citation Format: Kavitha Advikolanu Rao, Antony M. Magliocco, Andrew W. Maksymiuk. Aneuploidy, immunohistochemical overexpression of MSH-2, P53, P21^WAF1/CIP1, P16^INK4A, and correlation to epithelial ovarian carcinoma patient prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2045.