Open AccessPretreatment biopsy analysis of DAB 2 IP identifies subpopulation of high‐risk prostate cancer patients with worse survival following radiation therapy
Author(s) -
Jacobs Corbin,
Tumati Vasu,
Kapur Payal,
Yan Jingsheng,
Xie XianJin,
Hannan Raquibul,
Hsieh JerTsong,
Kim Dong Wook Nathan,
Saha Debabrata
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.554
Subject(s) - prostate cancer , medicine , prostate , metastasis , cancer , genitourinary system , urology , immunohistochemistry , radiation therapy , univariate analysis , biopsy , oncology , multivariate analysis
Decreased expression of tumor suppressor DAB 2 IP is linked to aggressive cancer and radiation resistance in several malignancies, but clinical survival data is largely unknown. We hypothesized that pretreatment DAB 2 IP 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 DAB 2 IP ‐reduction. The median follow up times were 4.8 years and 5.3 years for patients in the DAB 2 IP ‐reduced group and DAB 2 IP ‐retained group, respectively. Patients with reduced DAB 2 IP demonstrated worse outcome compared to patients retaining DAB 2 IP , 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 DAB 2 IP 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 DAB 2 IP . This subpopulation with reduced DAB 2 IP has a suboptimal response and worse malignancy‐specific survival following radiation therapy and androgen deprivation. DAB 2 IP 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.