title: Prognostic value of INPP4B protein immunohistochemistry in ovarian cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.forename: L
authors.initials: L
authors.lastname: Salmena
authors.forename: P
authors.initials: P
authors.lastname: Shaw
authors.forename: I
authors.initials: I
authors.lastname: Fans
authors.lastname: McLaughlin
authors.forename: B
authors.initials: B
authors.lastname: Rosen
authors.forename: H
authors.initials: H
authors.lastname: Risch
authors.forename: C
authors.initials: C
authors.lastname: Mitchell
authors.forename: P
authors.initials: P
authors.lastname: Sun
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: J
authors.initials: J
authors.lastname: Kotsopoulos
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human