Fas gene mutations in prostatic: Intraepithelial neoplasia and concurrent carcinoma: Analysis of laser capture microdissected specimens

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signalin g through binding of Fas ligand. Mutations of the Fas gene might be involve d in proliferative diseases of the prostate by prolongation of programmed c ell death of prostatic epithelial cells. Using the laser capture microdisse ction method, Fas gene mutations were examined on genomic DNA extracted fro m lesions with high-grade prostatic intraepithelial neoplasia (HGPIN), a po ssible precursor of prostatic cancer (PCA), and from PGA, A total of 193 le sions, 111 with HGPIN, 55 with PCA, and 27 benign glands, were microdissect ed from 27 patients with PCA. Polymerase chain reaction-amplified products were directly sequenced. Loss of heterozygosity (LOH) was examined at four sites of known polymorphisms. Fas gene mutations were detected in HGPIN: 4 of 27 (14.8%) cases or 4 of 111 (3.6%) lesions. All were point mutations: t hree missense and one nonsense in the death domain. Benign proliferative gl ands adjoining HGPIN and/or PCA, and PCA never showed mutations. LOH was fo und in 31.3% of PCA and 25% of HGPIN lesions, but was never found in benign glands. Exclusive occurrence of Fas mutations in HGPIN might underlie the development of these lesions. Occasional findings of LOH in HGPIN and PCA s uggested that genetic instability might occur during the early phase of pro static carcinogenesis.