ALLELIC LOSS IN LOCALLY METASTATIC, MULTISAMPLED PROSTATE-CANCER

In order to determine whether retention or loss of potential tumor sup pressor loci that map to 8p, 10q, or 16q reflect genetic relationships among prostatic intraepithelial neoplasias (PINs), multicentric prima ry prostatic cancers, and regional lymph node metastases or are associ ated with the metastatic phenotype, we analyzed 19 cases of locally me tastatic prostate carcinoma (stage D1) utilizing polymerase chain reac tion techniques. In each case, tissue samples from metastatic tumor, t he (dominant) primary tumor, and nonneoplastic prostatic tissue were e xamined. In selected cases, allelic loss in additional tumor foci, sep arate 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. Dis crepancies in sequence dosage between histological components were mos t pronounced for 8p sequences, especially between the dominant tumor n odule and metastatic deposits in cases in which greater than or equal to 3 separate tumor foci/gland were identified. These results suggest that putative premalignant lesions, moderately or poorly differentiate d, geographically separate primary tumor foci, and metastases within m orphologically ''complex'' prostates (those with greater than or equal to 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 compl ex prostates and that accumulation of genetic aberration may differ in primary and metastatic lesions.