Phosphorylated akt and phosphorylated mtor expression in breast invasive carcinomas: Analysis of 530 cases

Jungsuk An, Hoiseon Jeong, Youngseok Lee, Sang Uk Woo, Jae Hong Seo, Aeree Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: The phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) pathway has a central role in regulation of cell proliferation, differentiation, motility and survival. This pathway has recently generated great interest because its elements are, potentially, novel targets for the treatment of various malignancies, including breast cancer. Methods: Using tissue microarray sections of breast carcinoma, we performed immunohistochemical studies using antibodies against the phosphorylated forms of Akt (p-Akt) and mTOR (p-mTOR) in 530 invasive breast carcinomas and 30 ductal carcinomas in situ (DCIS). We investigated possible associations between expression of these proteins and clinicopathologic characteristics and disease outcomes. Results: In 530 invasive carcinomas, weak and strong expression of p-Akt was observed in 180 (34.0%) and 288 (54.3%) cases, respectively. The expression of p-Akt was associated with expression of estrogen receptors (ER) (p=0.045), progesterone receptors (PR) (p=0.003), lymph node metastasis (p<0.001) and cancer stage (p=0.027). Weak and strong expression of p-mTOR was found in 136 (25.7%) and 207 (39.1%) cases, respectively. The mTOR pathway was more frequently activated in DCIS than in invasive breast carcinoma (p=0.001). p-mTOR expression was associated with expression of ER (p=0.040), PR (p=0.009), tumor size (p<0.001), and stage (p=0.002). In a univariate analysis, strong expression of p-Akt was associated with longer disease-free survival (DFS). In a multivariate analysis, neither p-Akt nor p-mTOR was associated with DFS. Conclusion: The PI3K/Akt/mTOR pathway is active in DCIS as well as in invasive carcinoma of the breast. Our study also suggests that the PI3K/Akt/mTOR pathway is influenced by ER rather than erbB-2, and that this pathway may contribute more to cancer pathogenesis in ER-positive tumors.

Original languageEnglish
Pages (from-to)337-348
Number of pages12
JournalJournal of Breast Cancer
Volume13
Issue number4
DOIs
Publication statusPublished - 2010 Dec 1

Keywords

  • Breast
  • Carcinoma
  • Proto-oncogene protein c-akt
  • mTOR protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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