ISSN:
1432-1335
Keywords:
ras
;
Proliferation
;
mibl
;
Ki-67
;
Renal cell carcinoma
;
Tumor heterogeneity
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The variable prevalence and a possible stage-dependent increase ofras gene point mutations in human tumors might correspond to clonal growth advantages ofras-activated cells. Tumor areas with activatedras genes might thus differ in proliferative activity from those lackingras gene activation. This hypothesis is studied in a series of human renal cell carcinomas that had been used previously for an analysis of proliferative compartments after post-operative vascular [3H]/[14C]thymidine perfusion [Rabes et al. (1979) Cancer 44: 799–813]. The growth fraction of different subcompartments of these tumors was studied by immunohistochemistry with mib1 antibody, recognizing a fixation- and embedding-resistant epitope of Ki-67 protein. Thirty subpopulations of 14 human renal cell carcinomas that exhibited a broad spectrum of proliferative activity were chosen for an analysis of the prevalence of K-ras point mutations in exon 1 by a mutation-enriching primermediated restriction-fragment-length-polymorphism analysis and/or direct sequencing of polymerase-chain-reaction-amplified material. The combined autoradiographic and immunohistochemical analysis confirmed the intra- and intertumoral proliferative heterogeneity. Compared to [3H]/[14C]thymidine labeling indices, mib1 labeling indices are higher. The ratio of mib1 to [3H]/[14C]thymidine labeling indices varies from 1.9 to 4.1 for the individual tumor subcompartments. However, neither in K-ras codons 12/13 nor in adjacent codons did we detect any mutations in the various tumor compartments. The results suggest that neither mode of proliferation nor type of differentiation is related to K-ras exon 1 point mutations in human renal cell carcinomas.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01209647
Permalink
