PTEN Genetic and Epigenetic Alterations Define Distinct Subgroups in North Indian Breast Cancer Patients

Background: Breast cancer is a heterogeneous disease that can be subdivided on the basis of histopathologicalfeatures, genetic alterations, and gene-expression profiles. PTEN gene is considered an established tumor suppressor genein different types of cancer including breast cancer. However, the role of PTEN alterations in north Indian breast cancerhas not been explored especially in defining a group with distinct histological factors. Methodology: 181 sporadic breastcancer and their adjacent normal tissues were included in the present study. We analyzed methylation and LOH throughMS-PCR and microsatellite markers respectively. While, for PTEN protein expression, we used immunohistochemistry.All the molecular findings were correlated with the clinicopathological parameters of the patients to underline clinicalrelevance. Results: We found that LOH and methylation of the PTEN promoter were significantly associated withloss of PTEN protein expression, while, PTEN mutation was a rare event. Furthermore, out of 46 double hit cases (i.e.,having both methylation and LOH), 70% (32/46) cases showed complete loss of PTEN expression (P= 0.0249). BothLOH and PTEN promoter methylation were associated significantly with age and clinical stage, while, methylationand loss of PTEN expression were associated with high grade and Her-2 negativity. In addition, a quadruple (ER/PR/Her-2 and PTEN) negative group with distinct features was found. Conclusion: The pattern of PTEN expression andits correlation with the clinical parameters indicates that loss of PTEN expression defines a clinical group with distinctfeatures. Hence, PTEN expression provides differential therapeutic strategies for north Indian breast cancer.