PATHOLOGICAL FEATURES OF HEREDITARY PROSTATE-CANCER

The aim of this study was to characterize the pathological features of hereditary prostate cancer, a recently recognized variant of prostate cancer with an autosomal dominant inheritance of a rare highly penetrant gene associated with early onset of disease. We compared the histology at radical prostatectomy of clinical stage T2 prostate cancer, including its relationship to prostatic intraepithelial neoplasia, in men with a family history of prostate cancer to those without a family history of prostate cancer. Three cohorts (hereditary, familial and sporadic) were identified based on pedigree analysis. A hereditary subgroup (28 patients) met 1 of the following 3 criteria: 1) cluster of greater than 3 affected relatives within the nuclear family, 2) occurrence of prostate cancer in each of 3 generations in either the proband paternal or maternal lineage, or 3) a cluster of 2 relatives affected at an early age of less than 55 years. This subgroup was compared to an age-matched subgroup with family history of prostate cancer (26 patients) yet the aforementioned conditions for inclusion within the hereditary subgroup were not met and to a sporadic subgroup without a family history of prostate cancer (27 patients). All parameters were statistically similar among the groups except that hereditary and familial group multifocal tumors were of lower grade (p = 0.0001), sporadic cases had a greater proportion of small multifocal cancers associated with prostatic intraepithelial neoplasia (p = 0.02) and the familial group had a weaker correlation between total tumor volume and grade. In conclusion, our analysis failed to demonstrate substantial pathological differences among hereditary, familial and sporadic forms of prostate cancer. Rather, our data are remarkable for the wide range of all parameters studied in each group. Even the sporadic cases had features, such as increased numbers of precursor lesions and tumor multifocality, which in other organs are commonly associated with either hereditary cancer or cancer arising in a field effect due to diffuse exposure to a carcinogen.