Fan K
Department of Pathology, John L. McClellan Memorial Veterans Hospital, Little Rock, Arkansas.
J Urol. 1988 Feb;139(2):318-22. doi: 10.1016/s0022-5347(17)42397-4.
Expression of the p21 protein of the ras oncogene family was studied in a case of human prostatic adenocarcinoma tissue and the cell line was derived from the primary tumor. Flow cytometry analysis of the tumor cells obtained from the primary tumor indicated that approximately 25 per cent of the cells were positive for this oncogene product. However, by the immunoperoxidase method almost all of the tumor cells at the vertebral metastatic sites in the same patient were positive for the p21 protein. The cell line established from the primary tumor displayed 2 distinct subpopulation growth patterns in vitro: a monolayer, density-inhibited growth and a multicellular aggregate type growth morphology. These 2 subpopulations could be separated by density elutriation centrifugation. The isolated subpopulation cells were noted to express prostatic acid phosphatase and prostate specific antigen at high frequency. High levels of expression of these 2 prostatic markers also were found in the tumor cells at the vertebral metastatic sites. However, when the isolated subpopulations were analyzed for the expression of p21 protein, the multicellular grown cells were almost 90 per cent positive for the p21 antigen, whereas only approximately 5 per cent of the monolayer grown cells were positive for the same protein. Our findings suggest that primary prostatic carcinomas are composed of heterogeneous subpopulations of neoplastic cells while only specific subpopulations have metastatic potential. Quantification of prostatic acid phosphatase and prostate specific antigen in the primary tumor cells probably will not offer a predictive value for the eventual behavior of the tumors. However, evaluation of oncogene products, such as the p21 protein, may be useful as a clinical predictor for metastatic potential.
在一例人前列腺腺癌组织中研究了ras癌基因家族p21蛋白的表达,其细胞系源自原发性肿瘤。对原发性肿瘤获得的肿瘤细胞进行流式细胞术分析表明,约25%的细胞对该癌基因产物呈阳性。然而,通过免疫过氧化物酶法,同一患者椎体转移部位的几乎所有肿瘤细胞对p21蛋白呈阳性。从原发性肿瘤建立的细胞系在体外显示出两种不同的亚群生长模式:单层、密度抑制生长和多细胞聚集体类型生长形态。这两个亚群可以通过密度淘析离心分离。分离出的亚群细胞被发现高频表达前列腺酸性磷酸酶和前列腺特异性抗原。在椎体转移部位的肿瘤细胞中也发现了这两种前列腺标志物的高表达水平。然而,当对分离出的亚群进行p21蛋白表达分析时,多细胞生长的细胞对p21抗原的阳性率几乎为90%,而单层生长的细胞中只有约5%对同一蛋白呈阳性。我们的研究结果表明,原发性前列腺癌由肿瘤细胞的异质性亚群组成,而只有特定亚群具有转移潜能。对原发性肿瘤细胞中的前列腺酸性磷酸酶和前列腺特异性抗原进行定量分析可能无法为肿瘤的最终行为提供预测价值。然而,对癌基因产物,如p21蛋白的评估,可能作为转移潜能的临床预测指标有用。