Vaishnavi T

India

Somatic PTEN Alterations in an Indian Endometrial Cancer Cohort: Prevalence and Therapeutic Implications.

Vaishnavi.T1, Dr Tina Bhardwaj1
1.Department of Oncogenomics, Lifecell Diagnostics, No. 26, Vandalur-Kelambakkam Main Road, Keelakottaiyur, Chennai, Tamil Nadu, India.

Abstract

Background

Endometrial carcinoma (EC) is one of the most common gynecological malignancies globally. The tumor suppressor gene PTEN is a critical regulator of the PI3K/AKT/mTOR signaling pathway, and its somatic mutations are frequently reported in Type I (endometrioid) EC. While PTEN alterations serve as key molecular drivers and potential targets for therapeutic strategies, data regarding the prevalence and associated clinical implications in diverse ethnic groups, particularly in the Indian population, remain limited. This study investigates the prevalence of PTEN gene mutations and assesses their clinical and therapeutic relevance in an Indian cohort of patients with established EC. The primary aim of this study is to determine the prevalence of PTEN gene mutations and to assess their clinical and therapeutic relevance within an Indian cohort of patients diagnosed with endometrial carcinoma (EC).

Methods

This study included 117 consecutive adult female patients with histologically confirmed endometrial carcinoma. Formalin fixed paraffin embedded blocks with more than 20% tumor content were used for molecular test, DNA was extracted with manual extraction method. The inclusion criteria mandated clear documentation of clinical history, histopathology report and the presence of PTEN genetic alterations, defined as either pathogenic variants or variants of unknown significance (VUS). Patients with PTEN synonymous variants, germline variants, or those with poor quality tissue samples insufficient for molecular analysis were excluded. Oncolife Endometrial panel-21 Genes was performed with Next generation Sequencing (NGS) on MGI DNBseq T7 sequencer platform to identify somatic PTEN mutations, and clinical data were analyzed to correlate mutation status with established prognostic factors and therapeutic outcomes by the Molecular Pathologist.

Results

The final study cohort comprised 117 patients with established endometrial carcinoma. Molecular analysis for PTEN mutations revealed the presence of genetic alterations in 61 patients, corresponding to a high prevalence rate of 52.13% (61/117). The study successfully documented the specific PTEN mutation status (either pathogenic, likely pathogenic or VUS) for all 61 cases. Further analysis of the cohort demonstrated that the presence of a somatic PTEN mutation was significantly associated with certain clinicopathological features, which will be presented, highlighting its utility as a molecular marker for disease stratification and prognosis.

Conclusions

PTEN gene mutations are highly prevalent in this Indian cohort of endometrial carcinoma patients, affecting over half of the cases studied. This high frequency underscores the pivotal role of PTEN loss in the pathogenesis of EC within this population. Routine molecular screening for PTEN mutation status is warranted, as this information can facilitate the adoption of personalized medicine approaches, potentially guiding decisions toward targeted therapies that exploit the PI3K/AKT pathway for improved patient outcomes.