Focal Prostate Atrophic Lesions and Risk of Lethal Prostate Cancer.
Sabina Davidsson, Michelangelo Fiorentino, Ove Andren, Fang Fang, Lorelei A Mucci, Eberhard Varenhorst, Katja Fall, Jennifer R Stark. Orebro University Hospital, Orebro, Sweden; Bologna University, Italy; Brigham & Women´s Hospital, Boston, MA; Harvard School of Public Health, Boston, MA; Linkoping University Hospital, Linkoping, Sweden; Karolinska Institute, Stockholm, Sweden
Background: Repeated tissue damage and regeneration in a highly reactive microenviroment may contribute to cancer development and progression, including prostate cancer. Chronic inflammation in the prostate is often associated with focal glandular atrophy, especially post-atrophic hyperplasia (PAH) and simple atrophy (SA). It has been hypothesized that these lesions in the presence of inflammation may represent a precursor of prostate cancer (PCa).
Design: We investigated PIA and cancer mortality in a cohort of Swedish men diagnosed through TURP between 1977-99 with early PCa stage T1a-b tumors. We utilized an “extreme” case-control design by selecting as cases men who died of PCa within 10 years after diagnosis (n=228) and as controls men who survived more than 10 years after PCa diagnosis without any metastases (n=387). Slides were assessed for Gleason grade, presence and type of inflammation. Focal prostate atrophy was characterized according to a new atrophic classification. We used multivariable logistic regression to calculate odds ratios (OR) and 95% Confidence Intervals (CI).
Results: We identified chronic inflammation in 74% of the specimens. SA (59.4%) and PAH (20.3%) were the two most common atrophy lesions present. We found that HGPIN was more frequently observed in tumors with evidence of PAH (22% PAH positive vs.11% PAH negative; p<0.001). We found no overall association between either SA or PAH and lethal PCa. However, the association between PAH and lethal PCa was modified by degree of chronic inflammation (p-interaction =0.02). In patients with moderate or severe chronic inflammation the presence of PAH was associated with a 2-fold increased risk of PCa death compared to those without evidence of PAH (OR: 2.05; 95% CI: 0.81-5.21).
Conclusions: This study provides evidence that PAH lesions may have prognostic significance for PCa in the presence of inflammation. Chronic inflammation was a common feature in men with PCa and present in almost all specimens with evidence of PAH. HGPIN was more frequently observed in tumors with PAH present. A higher frequency of PAH lesions in an environment of chronic inflammation may result in more cells sensitive to DNA alterations, enhancing the potential for epithelial transformations that may lead to lethal PCa.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 71, Wednesday Morning