Immunohistochemical Study of DNA Repair Related Proteins in Sporadic Ovarian Cancer
J Castellvi, A Garcia, A Perez-Benavente, MC Ruiz-Marcellan, F Marginean, D Badia, C Parada, S Ramon y Cajal. Vall de Hebron Hospital. Universitat Autonoma de Barcelona, Barcelona, Spain
Background: Molecules involved in DNA repair, like BRCA, are related with hereditary ovarian carcinoma development, and have also been found downregulated in sporadic ovarian cancers although only nuclear expression of BRCA1 has been evaluated. In the complex DNA repair machinery other molecules, like PARP1 and PML, have been less studied, and their implication in the response to therapy is unknown. The aim of our work is to analyze the level and the cellular pattern of expression of these molecules in sporadic ovarian cancers, correlating them with the pathological characteristics of the tumors and their clinical outcome.
Design: We selected 42 patients with sporadic ovarian carcinomas that recurred after cisplatin and taxol chemotherapy. Immunohistochemistry for BRCA1 (GLK-2), PARP (A6.4.12) and PML (PG-M3) was performed on paraffin sections. The percentage of positive cells, its subcellular location, and the intensity of the staining were scored by two independent pathologists.
Results: BRCA1 nuclear expression was lost in 35% of cases and was found in the cytoplasm of 59% of the tumors. In all cases, non-tumor cells showed only nuclear expression. Similarly, PARP was lost in tumor cells in 47% of the cases. PML showed a speckled nuclear pattern, and was partially lost in 49% of cases. None of the three markers correlated with histologic type, grade or stage, although PML showed a tendency to be more strongly expressed in advanced stages. No correlation was found between the three proteins. The cases with higher expression of PARP recurred before 6 months (p=0.023), while in the survival analysis only BRCA1 cytoplasmic expression was significant (p=0.0026).
Conclusions: These results show that cytoplasmic subcellular location of BRCA1 expression has prognostic significance in ovarian tumors. Moreover, higher levels of PARP were observed in the cases that recurred before 6 months, suggesting that DNA repair is involved in the mechanism of chemoresistance, and that these patients could be candidates to be treated with PARP inhibitors. Finally, in our series PML expression does not correlate with prognosis in ovarian tumors.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 159, Wednesday Afternoon