Molecular Markers of Patient Outcome in Prostate Cancer Treated with Radiotherapy: Ki-67, Bcl-2, Bax, and Bcl-x

William Levin, MD
University of Pennsylvania Cancer Center
Last Modified: November 6, 2001

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Presenter: A. Pollack
Presenter's Affiliation: UT MD Anderson Cancer Center, Houston, TX
Type of Session: Scientific

Background
Abnormal expression of certain proteins have been found to alter the normal process of dying, or apoptosis, in cells. To date, there is little data correlating the presence of these proteins with outcome after radiation therapy for prostate cancer. This study looks at the relationship between the expression of Ki-67, Bcl-2, Bax, and bcl-x from pretreatment biopsy specimens and patient outcome after definitive radiotherapy alone.

Materials and Methods

  • Pre-treatment tissue biopsies of 106 men treated with external beam radiation therapy between 1987-1993 were obtained.
  • Median follow-up was 62 months.
  • Imunohistochemical staining was used to determine expression of Ki-67, Bcl-2, Bax, and bcl-x.
  • Biochemical failure after radiotherapy was defined as 3 consecutive rises in PSA on follow-up.

    Results

  • 5 year rates of freedom from biochemical failure (bNED) were inferior in those patients with tumors having a high Ki67-Labeling Index (>3.5%).
  • Positive Bcl-2 and altered Bax staining were also related to increased failure.
  • There was no relationship between bcl-x staining and biochemical failure.
  • Multivariate analysis showed that Bcl-2 and Bax were independent of pretreatment PSA, Gleason score, and stage in predicting biochemical failure.

    Author's Conclusions
    Abnormal expression of Bcl-2 and Bax is correlated with increased failure after external beam radiotherapy. Bax overexpression and underexpression are both correlated with biochemical failure. Increased expression of KI 67 also is predictive of poor outcome.

    Clinical/Scientific Implications
    In the future, screening pre-treatment tissue samples for expression of certain proteins might help identify patients at high risk for treatment failure. This information could be used when choosing therapy and when designing clinical trials.

    Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology and Pharmacia Oncology.


    News
    BCL2L1 Linked to Colorectal Cancer-Related Processes

    Aug 31, 2011 - BCL2L1 is involved in several colorectal cancer-related processes and its protein expression is associated with chromosome 20q gain, according to a study published online Aug. 18 in The Journal of Pathology.



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