DIFFERENT PATTERNS OF P53 MUTATIONS IN PROSTATIC INTRAEPITHELIAL NEOPLASIA AND CONCURRENT CARCINOMA - ANALYSIS OF MICRODISSECTED SPECIMENS

Prostatic intraepithelial neoplasia (PIN) is characterized by intralum inal proliferation of epithelial cells and can be divided into high-gr ade (HGPIN) and low-grade (LGPIN) lesions. HGPIN is regarded as the mo st likely precursor of prostatic carcinoma (PCA). Microdissected DNA s electively extracted from paraffin-embedded sections of 29 cases of PC A and 1 benign prostatic hypertrophy were analyzed for p53 mutation by single-strand conformation polymorphism (SSCP) of polymerase chain re action (PCR)-amplified DNA fragments followed by direct sequencing. Th ese patients had received total prostatectomy (27 cases) or transureth ral resection (3 cases). Under direct microscopic observation, DNA was microdissected from 108 lesions: 67 lesions from 22 cases of PIN (55 HGPIN and 12 LGPIN), 29 from 22 cases of PCA, and 12 from 11 cases of adjoining benign glands. Analysis revealed 13 mutations in 10 lesions from six cases. All 13 were point mutations: 7 missense, 5 silent, and 1 nonsense. Mutations were detected in 3 cases (14%) of PIN and 5 cas es (25%) of PCA. PIN lesions with p53 mutations were all categorized a s HGPIN. Neither LGPIN nor benign glands adjoining PIN and/or PCA had mutations. Two PIN and one PCA lesion in each of two cases had mutatio ns that were different from each other. G-to-A transition was the comm onest mutation pattern. The current findings showed that HGPIN, but no t LGPIN, and PCA are similar with regard to p53 mutation. The diverse patterns of p53 mutation among HGPIN and PCA lesions suggested multicl onal development of prostatic precancerous lesions.