Journal article
Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy
Cancer medicine (Malden, MA), Vol.4(12), pp.1844-1852
12/2015
DOI: 10.1002/cam4.554
PMCID: PMC4940806
PMID: 26471467
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.
Details
- Title: Subtitle
- Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy
- Creators
- Corbin Jacobs - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Vasu Tumati - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Payal Kapur - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Jingsheng Yan - Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Xian-Jin Xie - Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Raquibul Hannan - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Jer-Tsong Hsieh - Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Dong Wook Nathan Kim - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390Debabrata Saha - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
- Resource Type
- Journal article
- Publication Details
- Cancer medicine (Malden, MA), Vol.4(12), pp.1844-1852
- DOI
- 10.1002/cam4.554
- PMID
- 26471467
- PMCID
- PMC4940806
- NLM abbreviation
- Cancer Med
- ISSN
- 2045-7634
- eISSN
- 2045-7634
- Publisher
- United States
- Grant note
- CA175879 / NCI NIH HHS R21 CA175879 / NCI NIH HHS
- Language
- English
- Date published
- 12/2015
- Academic Unit
- Preventive and Community Dentistry; Biostatistics; Dental Research
- Record Identifier
- 9983917779202771
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