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Genetic heterogeneity of surgically resected prostate carcinomas and their biopsy specimens is related to their histologic differentiation
Author(s) -
Takimoto Yasuhiko,
Shimazui Toru,
Akaza Hideyuki,
Sato Nakako,
Noguchi Masayuki
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20010115)91:2<362::aid-cncr1010>3.0.co;2-3
Subject(s) - loss of heterozygosity , microdissection , pathology , prostate , biology , microsatellite , biopsy , carcinoma , polymerase chain reaction , laser capture microdissection , carcinogenesis , medicine , cancer , gene , genetics , allele , gene expression
BACKGROUND In human prostate carcinogenesis, many genetic analyses including conventional loss of heterozygosity (LOH) studies and microsatellite LOH analyses using the polymerase chain reaction method have revealed frequent LOH events at specific regions on chromosomes 3p, 7q, 8p, 10q, 16q, 17q, and 18q. METHODS Using the laser‐captured microdissection method, the authors extracted genomic DNA from 23 cases of prostate carcinomas including 59 different lesions and 8 biopsy specimens. Using 32 P‐labeled primers, the authors analyzed six microsatellite loci (D3S647, D3S1228, D7S522, D8S137, NEFL, and D10S190) at which frequent LOH events have been reported. RESULTS Of 10 cases in which the authors found LOH at any of the loci, 8 cases showed a heterogeneous LOH pattern. In four cases, the authors also found replication error (RER) at some of the loci examined. There was no significant relation between histologic differentiation and frequency of LOH or RER events. The overall LOH rate was found to be significantly lower in foci at classification pT2 (1 of 28 foci, 3%) compared with those at classification pT3 (13 of 44 foci, 30%). In pT3 samples, LOH events in extraglandular foci (9 of 23 foci, 39%) tended to be more frequent compared with those in intraglandular foci (8 of 41 foci, 20%). The patterns of LOH events in biopsy specimens correlated well with those in foci from surgical material showing the same histologic characteristics. CONCLUSIONS Prostate carcinoma is a genetically multicentric carcinoma, and the genetic heterogeneity is well correlated with histologic differentiation. The frequency of LOH events increased according to the degree of tumor progression. Cancer 2001;91:362–70. © 2001 American Cancer Society.