K-ras activation andras p21 expression in latent prostatic carcinoma in Japanese men

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Abstract
Twenty‐three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto‐oncogene mutations by mutation‐specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin‐fixed, paraffin‐embedded tissue. Six of the 22 that were satisfactorily amplified contained activating point mutations in codon 12 of K‐ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K‐ras, one had a GGT → GAT transition, four had GGT → GTT trans‐versions, and one had both GGT → GAT and GGT → GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti‐ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K‐ras mutation. K‐ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.