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Purpose <p>Very often endometrioid endometrial carcinoma (EEC) arises in the setting of endometrial hyperplasia (EH). The area of endometrial neoplastic precursor lesions and their progression into cancer phenotypes mediated by Akt/mTOR pathway are under reported. In the present study, we determined the immunohistochemical expression of proteins (Akt, mTOR, and eIF-4E) of this pathway in EH along with EEC to assess the role of Akt/mTOR pathway in the initial stage of endometrial carcinogenesis. This may aid the development of additional potent molecular therapies at its earliest stages.</p> Methods <p>It was a prospective observational case–control study included biopsies of normal proliferative endometrium (<i>n</i> = 23), EH with and without atypia (<i>n</i> = 39), and EEC (<i>n</i> = 40). Biopsies were collected in 10% neutral formalin for routine histology and immunohistochemistry of pAKT, pMTOR, and eIF-4E. Statistical analysis was performed using version 22.0 SPSS software, and to assess association, Chi-square test was carried out.</p> Results <p>A total of 102 endometrial biopsies were assessed. Age ranged from 30 to 70&#xa0;years. Positive immunoexpression of pAkt, pMTOR, and eIF-4E was observed in 65%, 63%, 93% of EEC cases, respectively, and 80%, 70%, 100% of EH with atypia cases.</p> Conclusion <p>Upregulation of pAKT, pMTOR, and eIF-4E was observed in EH with atypia along with EEC cases suggesting that activation of Akt/mTOR pathway might be the initial step in endometrial carcinogenesis. A better understanding of the molecular process of this pathway may aid in the development of additional potent molecular therapies at its earliest stages.</p>

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Akt/mTOR Pathway in Endometrioid Endometrial Cancer and Precursor Lesions

  • 期刊论文

  • 发表日期：

    2025年10月24日

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  • Sunita Yadav,
  • Annu Makker,
  • Nikki Gupta,
  • Seema Nayak,
  • Uma Singh,
  • Madhu Mati Goel

摘要

Purpose

Very often endometrioid endometrial carcinoma (EEC) arises in the setting of endometrial hyperplasia (EH). The area of endometrial neoplastic precursor lesions and their progression into cancer phenotypes mediated by Akt/mTOR pathway are under reported. In the present study, we determined the immunohistochemical expression of proteins (Akt, mTOR, and eIF-4E) of this pathway in EH along with EEC to assess the role of Akt/mTOR pathway in the initial stage of endometrial carcinogenesis. This may aid the development of additional potent molecular therapies at its earliest stages.

Methods

It was a prospective observational case–control study included biopsies of normal proliferative endometrium (n = 23), EH with and without atypia (n = 39), and EEC (n = 40). Biopsies were collected in 10% neutral formalin for routine histology and immunohistochemistry of pAKT, pMTOR, and eIF-4E. Statistical analysis was performed using version 22.0 SPSS software, and to assess association, Chi-square test was carried out.

Results

A total of 102 endometrial biopsies were assessed. Age ranged from 30 to 70 years. Positive immunoexpression of pAkt, pMTOR, and eIF-4E was observed in 65%, 63%, 93% of EEC cases, respectively, and 80%, 70%, 100% of EH with atypia cases.

Conclusion

Upregulation of pAKT, pMTOR, and eIF-4E was observed in EH with atypia along with EEC cases suggesting that activation of Akt/mTOR pathway might be the initial step in endometrial carcinogenesis. A better understanding of the molecular process of this pathway may aid in the development of additional potent molecular therapies at its earliest stages.