In order to determine whether retention or loss of potential tumor suppressor loci that map to 8p, 10q, or 16q reflect genetic relationships among prostatic intraepithelial neoplasias (PINs), multicentric primary prostatic cancers, and regional lymph node metastases or are associated with the metastatic phenotype, we analyzed 19 cases of locally metastatic prostate carcinoma (stage D1) utilizing polymerase chain reaction techniques. In each case, tissue samples from metastatic tumor, the (dominant) primary tumor, and nonneoplastic prostatic tissue were examined. In selected cases, allelic loss in additional tumor foci, separate from the dominant tumor nodule, and areas of PIN were examined. Allelic loss of sequences on 8p, 10q, and 16q were observed in 20–29% of PINs, 18–42% of primary tumors, and 8–25% of metastatic tumors. Discrepancies in sequence dosage between histological components were most pronounced for 8p sequences, especially between the dominant tumor nodule and metastatic deposits in cases in which ≥3 separate tumor foci/gland were identified. These results suggest that putative premalignant lesions, moderately or poorly differentiated, geographically separate primary tumor foci, and metastases within morphologically “complex” prostates (those with ≥3 foci/gland) are likely to be more discordant for sequence dosage at 8p than those within “simpler” glands (<3 foci/gland). Also, our results suggest that lymph node metastases may be genetically related to either the dominant or additional primary tumor foci in more complex prostates and that accumulation of genetic aberration may differ in primary and metastatic lesions.
This work was supported, in part, by a grant from Merck, Sharpe and Dohme and funds from the Departments of Pathology and Urology, Wayne State University School of Medicine, Detroit, MI.