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PTEN expression and morphological patterns in prostatic adenocarcinoma.

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Cribriform prostate cancer patterns, including intraductal carcinoma (IDCP), predict poor prognosis and biochemical recurrence (BCR). PTEN loss within glomeruloid morphology is linked to BCR, but not significantly with invasive cribriform carcinoma.

Keywords:
biochemical recurrencecribriformintraductal carcinomapathologyprostate cancer

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Area of Science:

  • Uropathology
  • Prostate Cancer Research
  • Molecular Oncology

Background:

  • Cribriform morphology in prostate cancer, encompassing intraductal carcinoma (IDCP) and invasive cribriform carcinoma, is linked to unfavorable prognosis.
  • Loss of Phosphatase and tensin homologue (PTEN) expression is a known predictor of adverse outcomes in cancer.
  • The relationship between PTEN expression and specific prostate cancer morphological patterns, particularly cribriform types, requires further elucidation.

Purpose of the Study:

  • To investigate the association between PTEN expression, various Gleason pattern 4 morphologies (including IDCP and invasive cribriform carcinoma), and biochemical recurrence (BCR) in prostate cancer.
  • To determine if PTEN loss modifies the prognostic impact of cribriform patterns on BCR.
  • To explore the prognostic significance of glomeruloid morphology and its relationship with PTEN loss in relation to BCR and cancer staging.

Main Methods:

  • Analysis of 163 radical prostatectomy specimens using immunohistochemistry to assess PTEN expression.
  • Morphological evaluation, including the distinction of IDCP from invasive cribriform carcinoma using p63 staining.
  • Statistical analysis to correlate morphological patterns and PTEN status with biochemical recurrence (BCR) and pT3 cancer stage.

Main Results:

  • Both invasive cribriform carcinoma and IDCP were significantly associated with a higher cumulative incidence of BCR (HR=5.06).
  • Invasive cribriform carcinoma remained an independent predictor of BCR (HR=3.72), whereas PTEN loss within this pattern was not significantly associated with BCR.
  • PTEN loss within glomeruloid morphology was associated with a higher cumulative incidence of BCR (HR=4.07), while glomeruloid morphology itself was associated with lower odds of pT3 stage and BCR (HR=0.27).

Conclusions:

  • PTEN loss within the glomeruloid pattern is a significant predictor of BCR in prostate cancer.
  • The presence of any cribriform pattern is associated with BCR, independent of PTEN loss in invasive cribriform carcinoma.
  • These findings suggest that other molecular drivers, beyond PTEN loss, may contribute to the poor prognostic features observed in cribriform prostate cancer.