PTEN mutation, expression and LOH at its locus in ovarian carcinomas. Relation to TP53, K-RAS and BRCA1 mutations

• Published in: Gynecologic oncology 2006-11, Vol.103 (2), p.692-697
• Main Authors: Kolasa, I.K., Rembiszewska, A., Janiec-Jankowska, A., Dansonka-Mieszkowska, A., Lewandowska, A.M., Konopka, B., Kupryjańczyk, J.
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BRCA1; Carcinoma, Endometrioid - drug therapy; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - metabolism; Female; Genes, BRCA1; Genes, p53; Genes, ras; Humans; Immunohistochemistry; K-RAS; Loss of Heterozygosity; Mutation; Organoplatinum Compounds - administration & dosage; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; PTEN; PTEN Phosphohydrolase - biosynthesis; PTEN Phosphohydrolase - genetics; TP53
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2006.05.007

We aimed to evaluate frequency of PTEN mutation, LOH and expression in ovarian tumors. In search for a molecular pathway, we confronted PTEN gene mutations with TP53, K-RAS and BRCA1 gene status in the same tumors. We also evaluated clinical significance of PTEN expression in a subgroup of patients uniformly treated with platinum-based regimens. Molecular analysis was performed on 105 ovarian tumors (100 carcinomas) with the use of the SSCP and sequencing. Seventy-six tumors were analyzed for LOH at 10q23 locus with the use of six polymorphic markers. Immunohistochemical PTEN expression was done on paraffin-embedded material. Multivariate and univariate analysis was performed with the STATA program. PTEN mutations occurred in 5/100 (5%) of all carcinomas and in 3/15 (20%) of endometrioid carcinomas (EC). Low-grade EC that developed in borderline tumors had PTEN and/or K-RAS mutation (4/5, 80%), while high-grade EC had TP53 mutations only. There was a reverse association between PTEN and TP53 mutations ( P = 0.005). LOH at PTEN locus was found in 60% of endometrioid and in 28% of serous and clear cell carcinomas. PTEN expression did not associate with PTEN mutations or LOH. Strong PTEN expression diminished risk of death in a TP53 positive group only (HR = 0.35, P = 0.029). Our results suggest that PTEN mutations may play a role in a development of low-grade endometrioid tumors. PTEN haploinsufficiency caused by LOH or epigenetic events may possibly contribute to development of other histological types and may be an adverse prognostic factor.