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

Document Type : Research Articles


1 Department of Biosciences, Jamia Millia Islamia, New Delhi, India.

2 Department of Surgery, Maulana Azad Medical College,New Delhi, India.


Background: Breast cancer is a heterogeneous disease that can be subdivided on the basis of histopathological
features, genetic alterations, and gene-expression profiles. PTEN gene is considered an established tumor suppressor gene
in different types of cancer including breast cancer. However, the role of PTEN alterations in north Indian breast cancer
has not been explored especially in defining a group with distinct histological factors. Methodology: 181 sporadic breast
cancer and their adjacent normal tissues were included in the present study. We analyzed methylation and LOH through
MS-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 clinical
relevance. Results: We found that LOH and methylation of the PTEN promoter were significantly associated with
loss 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). Both
LOH and PTEN promoter methylation were associated significantly with age and clinical stage, while, methylation
and 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 and
its correlation with the clinical parameters indicates that loss of PTEN expression defines a clinical group with distinct
features. Hence, PTEN expression provides differential therapeutic strategies for north Indian breast cancer.


Main Subjects