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Prognostic value of INPP4B protein immunohistochemistry in ovarian cancer
L. Salmena1,2,3, P. Shaw4, I. Fan5, J.R. McLaughlin5, B. Rosen6, H. Risch7, C. Mitchell8, P. Sun3, S.A. Narod3,9, J. Kotsopoulos3,9,*
1 Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON
2 Princess Margaret Cancer Centre, University Health Network, Toronto, ON
3 Women’s College Research Institute, Women’s College Hospital, Toronto, ON
4 Department of Pathology, University Health Network, Toronto, ON
5 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, ON
6 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON (Canada);
7 Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT (USA);
8 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria (Australia);
9 Dalla Lana School of Public Health, University of Toronto, Toronto, ON (Canada)
Eur. J. Gynaecol. Oncol. 2015, 36(3), 260–267; https://doi.org/10.12892/ejgo2741.2015
Published: 10 June 2015
Purpose of investigation: Ovarian cancer is associated with poor prognosis and altered protein expression patterns may be useful for identifying patients likely to have poor disease outcomes. The impact of altered INPP4B protein expression on prognosis is unclear. The aim of this study was to evaluate the implication of INPP4B expression changes in a large series of ovarian cancer tissue samples. Materials and Methods: Tissue microarrays were constructed from 599 epithelial ovarian tumors and stained with antibodies for INPP4B, p53, and PTEN. Proportional hazard models were used to estimate survival hazard ratios (HRs) associated with altered protein expression. Results: Seventy-nine percent of the ovarian cancers demonstrated loss of INPP4B, whereas 53% showed aberrant p53 expression (i.e., complete loss of p53 or over-expression of p53) and 8% showed loss of PTEN. INPP4B was frequently lost in serous and endometrioid cancer subtypes, aberrant p53 expression was most common among serous subtype, and loss of PTEN was most common among endometrioid tumors (p for all three proteins across histologic subtypes ≤0.0001). INPP4B loss or aberrant p53 expression were both associated with increased mortality (HR = 1.84; 95% CI 1.27 - 2.68 and HR = 3.10; 95% CI 2.33 - 4.11, respectively); however, in multivariate models, only the relationship with p53 achieved statistical significance (HR = 1.20; 95% CI 0.82 - 1.76 for INPP4B and HR = 1.73; 95% CI 1.28 - 2.34 for p53). Conclusion: The INPP4B protein is frequently lost in serous and endometrioid subtypes of ovarian cancer. A possible prognostic role of INPP4B for endometrioid ovarian tumors requires further evaluation.