van Leenders G J, Aalders T W, Hulsbergen-van de Kaa C A, Ruiter D J, Schalken J A
Department of Pathology, University Medical Centre St. Radboud, Nijmegen, The Netherlands.
J Pathol. 2001 Dec;195(5):563-70. doi: 10.1002/path.993.
Within normal human prostate epithelium, basal and luminal cells can be discriminated by their expression of keratins (K). While basal cells express K5/14, luminal cells show expression of K8/18 and an intermediate cell population can be identified by co-expression of K5/18. Prostate cancer is predominantly composed of luminal and neuroendocrine cells, while a minority of cells have a basal phenotype. In order to distinguish between basal and intermediate cells, and to assess the effects of androgen deprivation on prostate cancer, 56 human prostate cancer metastases and three cancer cell lines were characterized using antibodies to K5, K14, K18, and the neuroendocrine marker chromogranin A (ChA). The staining was performed on paraffin tissue and visualized by the avidin-biotin-peroxidase complex method. Protein expression was quantified as the number of positive cells in 20 high power fields (HPF; 400x). Keratin expression in the prostate cancer cell lines LNCaP, DU145, and PC3 was analysed by immunofluorescence with triple staining and confocal laser scanning microscopy. Prostate cancer metastases were consistently positive for K18 and negative for K14, irrespective of hormonal therapy. K5 expression was displayed in 28.9% of the tumours without treatment, in 75% after androgen deprivation, and in 57.1% of hormone-escaped prostate carcinomas. After androgen deprivation, the number of K5-expressing cells increased significantly. While androgen-dependent prostate cancer showed a median of 0 cells/20 HPF (range 0-50), regressed tumours displayed 22.5 (range 0-65) and hormone-escaped tumours 7.5 (range 0-361) positive cells/20 HPF. Expression of ChA was observed in 47.4% of the androgen-dependent tumours. The number of neuroendocrine cells was not significantly affected in regressed or hormone-escaped disease. The androgen-dependent cell line LNCaP stained for K18, while the androgen-independent lines DU145 and PC3 both expressed K5 and 18. Expression of K5 in the absence of K14 identifies the existence of an intermediate cell population in prostate carcinoma. Accumulation of intermediate cells in regressed and hormone-escaped prostate cancer indicates that for their survival, these cells are androgen-independent.
在正常人类前列腺上皮中，基底细胞和管腔细胞可通过其角蛋白（K）的表达来区分。基底细胞表达K5/14，管腔细胞表达K8/18，而中间细胞群体可通过K5/18的共表达来识别。前列腺癌主要由管腔细胞和神经内分泌细胞组成，而少数细胞具有基底细胞表型。为了区分基底细胞和中间细胞，并评估雄激素剥夺对前列腺癌的影响，使用针对K5、K14、K18和神经内分泌标志物嗜铬粒蛋白A（ChA）的抗体对56例人类前列腺癌转移灶和三种癌细胞系进行了表征。染色在石蜡组织上进行，并通过抗生物素蛋白-生物素-过氧化物酶复合物法进行可视化。蛋白质表达以20个高倍视野（HPF；400倍）中的阳性细胞数进行量化。通过三重染色免疫荧光和共聚焦激光扫描显微镜分析前列腺癌细胞系LNCaP、DU145和PC3中的角蛋白表达。无论激素治疗如何，前列腺癌转移灶K18始终呈阳性，K14呈阴性。28.9%未经治疗的肿瘤显示K5表达，雄激素剥夺后为75%，激素逃逸性前列腺癌为57.1%。雄激素剥夺后，表达K5的细胞数量显著增加。雄激素依赖性前列腺癌的中位数为0个细胞/20 HPF（范围0 - 50），消退肿瘤为22.5个（范围0 - 65），激素逃逸性肿瘤为7.5个（范围0 - 361）阳性细胞/20 HPF。在47.4%的雄激素依赖性肿瘤中观察到ChA表达。在消退或激素逃逸性疾病中，神经内分泌细胞的数量没有受到显著影响。雄激素依赖性细胞系LNCaP对K18染色，而雄激素非依赖性细胞系DU145和PC3均表达K5和18。在缺乏K14的情况下K5的表达表明前列腺癌中存在中间细胞群体。在消退和激素逃逸性前列腺癌中中间细胞的积累表明，为了生存，这些细胞不依赖雄激素。
