Genomic alterations in prostate high-grade intraepithelial neoplasia (HPIN) can be predictive of a more aggressive disease process.

摘要

High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate carcinoma (Pca). To determine whether chromosomal instability (CIN) detected in HPIN could increase its predictive value for cancer, interphase FISH analysis was performed on isolated HPIN. We found that CIN was elevated in HPIN that subsequently progressed to carcinoma. p53 mutation is associated with CIN in many dysplastic and neoplastic lesions. However the precise role of p53 in the pathogenesis of Pca is unknown. p53 analysis using immunohistochemistry was performed. HPIN foci intermingled with cancer tended to have higher overall p53 immunoreactivity and CIN than HPIN situated away. Our study provided additional evidence in support of the concept that HPIN is the earliest precursor of cancer. Furthermore our studies identify genomic similarities in HPINI and Pca, implying that carcinoma may arise from progression of certain HPIN foci that most likely harbor p53 mutation and/or more marked levels of CIN.