Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy

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Abstract:
Decreased expression of tumor suppressor DAB2IP is linked to aggressive cancer and radiation resistance in several malignancies, but clinical survival data is largely unknown. We hypothesized that pretreatment DAB2IP reduction would predict worse prostate cancer-specific survival (PCSS). Immunohistochemistry of pretreatment biopsies was scored by an expert genitourinary pathologist. Other endpoints analyzed include freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS). Seventy-nine patients with NCCN-defined high-risk prostate cancer treated with radiotherapy from 2005 to 2012 at our institution were evaluated. Twenty-eight percent (22/79) of pretreatment biopsies revealed DAB2IP-reduction. The median follow up times were 4.8 years and 5.3 years for patients in the DAB2IP-reduced group and DAB2IP-retained group, respectively. Patients with reduced DAB2IP demonstrated worse outcome compared to patients retaining DAB2IP, including FFBF (4-year: 34 vs. 92%; P < 0.0001), CRFS (4-year: 58 vs. 96%; P = 0.0039), DMFS (4-year: 58 vs. 100%; P = 0.0006), and PCSS (5-year: 83 vs. 100%;P = 0.0102). Univariate analysis showed T stage, N stage, and Gleason score were statistically significant variables. Pretreatment tumor DAB2IP status remained significant in multivariable analyses. This study suggests that about one-fourth of men with high-risk prostate cancer have decreased tumor expression of DAB2IP. This subpopulation with reduced DAB2IP has a suboptimal response and worse malignancy-specific survival following radiation therapy and androgen deprivation. DAB2IP loss may be a genetic explanation for the observed differences in aggressive tumor characteristics and radiation resistance. Further study into improving treatment response and survival in this subpopulation is warranted.

Keywords:
Biomarker; DAB2IP; EZH2; prostate cancer; survival

Autoři: Corbin Jacobs ¹; Vasu Tumati ¹; Payal Kapur ²; Jingsheng Yan ³; Xian-Jin Xie ³; Raquibul Hannan ¹; Jer-Tsong Hsieh ⁴; Dong Wook Nathan Kim ¹; Debabrata Saha ^1,*
Působiště autorů: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas ¹; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas ²; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas ³; Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas ⁴
Vyšlo v časopise: Cancer Medicine 2015; Early View(Early View)
Kategorie: Original Research
prolekare.web.journal.doi_sk: https://doi.org/10.1002/cam4.554

© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Souhrn

Keywords:
Biomarker; DAB2IP; EZH2; prostate cancer; survival

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