Oncotarget

Research Papers: Pathology:

WT1, p53 and p16 expression in the diagnosis of low- and high-grade serous ovarian carcinomas and their relation to prognosis

Luis Felipe Sallum, Liliana Andrade, Susana Ramalho, Amanda Canato Ferracini, Rodrigo de Andrade Natal, Angelo Borsarelli Carvalho Brito, Luis Otávio Sarian and Sophie Derchain _

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Oncotarget. 2018; 9:15818-15827. https://doi.org/10.18632/oncotarget.24530

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Abstract

Luis Felipe Sallum1, Liliana Andrade2, Susana Ramalho1, Amanda Canato Ferracini3, Rodrigo de Andrade Natal4, Angelo Borsarelli Carvalho Brito5, Luis Otávio Sarian1 and Sophie Derchain1

1Department of Obstetrics and Gynecology, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, São Paulo, Brazil

2Department of Pathology, University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, São Paulo, Brazil

3Program in Medical Sciences, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, São Paulo, Brazil

4Laboratory of Investigative and Molecular Pathology, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, São Paulo, Brazil

5Laboratory of Cancer Genetics, State University of Campinas, Campinas, Faculty of Medical Sciences, Campinas, São Paulo, Brazil

Correspondence to:

Sophie Derchain, email: fsallum@unicamp.br

Keywords: cystadenocarcinoma; serous; diagnoses; survival; prognosis; Pathology

Received: September 28, 2017     Accepted: February 12, 2018     Epub: February 19, 2018      Published: March 23, 2018

ABSTRACT

Objective: To evaluate the diagnostic and prognostic value of the immunohistochemical expression of WT1, p53 and p16 in low- (LGSOCs) and high-grade serous ovarian carcinomas (HGSOCs).

Results: HGSOC had a significantly higher proportion of advanced stage disease, higher CA125 levels, higher proportion of post-surgery residual disease and higher recurrence or disease progression. WT1 was expressed in 71.4% of LGSOCs and in 57.1% of HGSOCs (p = 0.32). Focal and/or complete absence of p53 expression with negative p16 expression was found in 90.5% of LGSOCs, in contrast to the 88.1% of HGSOCs with diffuse or complete absence of p53 expression with positive p16 expression (<0.001). The IHC p53/p16 index and the morphological classification were closely matched (k = 0.68). In the univariate analysis, FIGO stage, post-surgery residual disease and histological grade were significantly associated with progression-free survival (PFS) and overall survival (OS). The IHC p53/p16 index was associated only with PFS. WT1 was not associated with PFS or OS. According to the multivariate analysis, advanced FIGO stage and presence of post-surgery residual disease remained independent prognostic factors for worst PFS, however these features had only a trend association with OS.

Methods: 21 LGSOC and 85 HGSOC stage I–IV cases were included. The morphological classification was assessed according to the World Health Organization (WHO) criteria. Immunohistochemistry (IHC) was performed in tissue microarray slides. IHC p53/p16 index was compared with the morphological classification.

Conclusions: The IHC p53/p16 index was a good marker for the differentiation of LGSOC and HGSOC, but the morphologic classification showed a better association with survival. FIGO stage and post-surgery residual disease remained the only independent prognostic factors for survival.


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