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PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement.

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  • 1Department of Medical Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume 447, 34149 Trieste, Italy.

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Summary

Gene expression differences in primary breast cancer (BC) correlate with lymph node involvement. Specific AKT gene expressions impact patient survival and may predict response to Tamoxifen treatment in certain BC subtypes.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lymph node metastasis is a key predictor of breast carcinoma (BC) recurrence and survival.
  • Understanding gene expression differences in primary tumors can identify prognostic markers.

Purpose of the Study:

  • To investigate gene expression variations in primary BC tumors based on lymph node involvement at diagnosis.
  • To explore the prognostic and predictive roles of candidate biomarkers, particularly those in the PI3K/AKT pathway.

Main Methods:

  • Retrospective analysis of 305 BC patients (151 LN-, 154 LN+).
  • RT-qPCR to assess mRNA levels of 9 candidate genes (RAS, RB, and cellular differentiation pathways).
  • Correlation of gene expression with molecular subtypes and clinical/pathological features.

Main Results:

  • Differential expression of genes like PIK3CB, RB1, AKT3 (higher in LN-), and ERBB2, AKT1 (higher in LN+) was observed.
  • AKT isoform expression levels significantly impacted patient survival.
  • AKT1 and AKT2 overexpression correlated with reduced overall survival; AKT2 specifically identified high-risk luminal B BC patients.

Conclusions:

  • The PI3K/AKT pathway exhibits complex regulation in BC, with distinct expression patterns in lymph node-negative versus lymph node-positive patients.
  • AKT3 expression is associated with longer survival in luminal A BC and may predict Tamoxifen response.
  • Candidate biomarkers, especially AKT isoforms, offer prognostic and predictive value in breast cancer management.