title: Intact PTEN Expression by Immunohistochemistry is Associated With Decreased Survival in Advanced Stage Ovarian/Primary Peritoneal High-grade Serous Carcinoma.
abstract: Ovarian high-grade serous carcinoma is an aggressive malignancy with poor prognosis. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are 2 well-established prognostics for this tumor type. Molecular markers that identify more clinically aggressive tumors would potentially allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with nonendometrioid tumors. The prognostic and predictive value for PTEN has not been effectively explored in ovarian/peritoneal high-grade serous carcinoma. PTEN immunohistochemistry was assessed in 126 women with Stage III, high-grade serous carcinoma of the ovary/peritoneum treated with surgery and then a platinum-based regimen. Compared with PTEN-negative or PTEN-reduced tumors, positive PTEN immunohistochemistry, detected in 58% of tumors, was associated with decreased pS6 and increased PTEN mRNA levels. Positive PTEN expression was independent of surgical debulking status or platinum sensitivity. PTEN-positive tumors were associated with significantly decreased recurrence-free survival. Importantly, the devised PTEN immunohistochemistry scoring system was reproducible among pathologists.
authors.affiliation: Departments of Pathology (R.B., S.-S.X., K.V., R.R.B.) Biostatistics (D.L.U.), University of Texas MD Anderson Cancer Center, Houston, Texas Eastern Ontario Regional Laboratory (B.D.), Department of Pathology and Laboratory Medicine, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: Rania M
authors.initials: RM
authors.lastname: Bakkar
authors.forename: Su-Su
authors.initials: SS
authors.lastname: Xie
authors.forename: Diana L
authors.initials: DL
authors.lastname: Urbauer
authors.forename: Bojana
authors.initials: B
authors.lastname: Djordjevic
authors.forename: Kim
authors.initials: K
authors.lastname: Vu
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018284:Cystadenocarcinoma, Serous / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human