前列腺叶状肿瘤上皮和间质成分不同克隆起源的分子遗传学证据。
Molecular genetic evidence for different clonal origins of epithelial and stromal components of phyllodes tumor of the prostate.
作者信息
McCarthy Ryan P, Zhang Shaobo, Bostwick David G, Qian Junqi, Eble John N, Wang Mingsheng, Lin Haiqun, Cheng Liang
机构信息
Department of Pathology and Laboratory Medicine, Indiana University Medical Center, University Hospital 3465, 550 North University Blvd., Indianapolis, IN 46202, USA.
出版信息
Am J Pathol. 2004 Oct;165(4):1395-400. doi: 10.1016/S0002-9440(10)63397-4.
Phyllodes tumor of the prostate is a rare neoplasm, composed of epithelium-lined cysts and channels embedded in a variably cellular stroma. The pathogenetic relationship of the epithelium and stroma is unknown and whether each is a clonal neoplastic element is uncertain. We studied the clonality of phyllodes tumors from six patients who underwent either enucleation or transurethral resection as their initial treatment. This was followed by total prostatectomy in three of the patients. Laser-assisted microdissection was performed to extract epithelial and stromal components of phyllodes tumor from formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 7q31 (D7S522), 8p21.3-q11.1 (D8S133, D8S137), 8p22 (D8S261), 10q23 (D10S168, D10S571), 17p13 (TP53), 16q23.2 (D16S507), 12q11-12 (D12S264), 17q (D17S855), 18p11.22-p11 (D18S53), and 22q11.2 (D22S264). In each tumor, stroma and epithelium were analyzed separately. Gel electrophoresis with autoradiography was used to detect loss of heterozygosity. All tumors showed allelic loss in one or more loci of both the epithelial and stromal components. The frequency of allelic loss in the epithelial component was 2 of 5 (40%) at D7S522, 2 of 6 (33%) at D8S133, 1 of 5 (20%) at D8S137, 3 of 6 (50%) at D8S261, 4 of 4 (100%) at D10S168, 4 of 6 (67%) at TP53, 2 of 6 (33%) at D10S571, 6 of 6 (100%) at D16S507, 1 of 5 (20%) at D12S264, 1 of 6 (17%) at D17S855, 2 of 6 (33%) at D18S53, and 2 of 5 (40%) at D22S264. The frequency of allelic loss in the stromal component was 2 of 5 (40%) at D7S522, 1 of 6 (17%) at D8S133, 2 of 5 (40%) at D8S137, 3 of 6 (50%) at D8S261, 1 of 4 (25%) at D10S168, 3 of 6 (50%) at TP53, 2 of 6 (33%) at D10S571, 3 of 6 (50%) at D16S507, 1 of 5 (20%) at D12S264, 0 of 6 (0%) at D17S855, 1 of 6 (17%) at D18S53, and 0 of 5 (0%) at D22S264. The pattern of allelic loss is significantly different in both stroma and epithelium statistically; completely concordant allelic loss patterns were not seen in any tumor examined. Our data demonstrate that both epithelial and stromal components of phyllodes tumor of the prostate are clonal, supporting the hypothesis that both elements are neoplastic. While both epithelium and stroma are clonal proliferations, they appear to have different clonal origins.
前列腺叶状肿瘤是一种罕见的肿瘤，由内衬上皮的囊肿和通道组成，包埋于细胞成分各异的间质中。上皮与间质之间的发病机制关系尚不清楚，且二者是否均为克隆性肿瘤成分也不确定。我们研究了6例接受剜除术或经尿道切除术作为初始治疗的患者的叶状肿瘤的克隆性。其中3例患者随后接受了前列腺全切术。采用激光辅助显微切割技术从福尔马林固定、石蜡包埋的组织中提取前列腺叶状肿瘤的上皮和间质成分。利用聚合酶链反应扩增7号染色体长臂31区（D7S522）、8号染色体短臂21.3区至长臂11.1区（D8S133、D8S137）、8号染色体短臂22区（D8S261）、10号染色体长臂23区（D10S168、D10S571）、17号染色体短臂13区（TP53）、16号染色体长臂23.2区（D16S507）、12号染色体长臂11区至12区（D12S264）、17号染色体长臂（D17S855）、18号染色体短臂11.22区至11区（D18S53）以及22号染色体长臂11.2区（D22S264）特定位点的基因组DNA。对每例肿瘤的间质和上皮分别进行分析。采用凝胶电泳及放射自显影检测杂合性缺失。所有肿瘤的上皮和间质成分在一个或多个位点均显示出等位基因缺失。上皮成分中等位基因缺失的频率在D7S522为5例中的2例（40%），在D8S133为6例中的2例（33%），在D8S137为5例中的1例（20%），在D8S261为6例中的3例（50%），在D10S168为4例中的4例（100%），在TP53为6例中的4例（67%），在D10S571为6例中的2例（33%），在D16S507为6例中的6例（100%），在D12S264为5例中的1例（20%），在D17S855为6例中的1例（17%），在D18S53为6例中的2例（33%），在D22S264为5例中的2例（40%）。间质成分中等位基因缺失的频率在D7S522为5例中的2例（40%），在D8S133为6例中的1例（17%），在D8S137为5例中的2例（40%），在D8S261为6例中的3例（50%），在D10S168为4例中的1例（25%），在TP53为6例中的3例（50%），在D10S571为6例中的2例（33%），在D16S507为6例中的3例（50%），在D12S264为5例中的1例（20%），在D17S855为6例中的0例（0%）,在D18S53为6例中的1例（17%），在D22S264为5例中的0例（0%）。在统计学上，间质和上皮的等位基因缺失模式均有显著差异；在所检测的任何肿瘤中均未发现完全一致的等位基因缺失模式。我们的数据表明，前列腺叶状肿瘤的上皮和间质成分均为克隆性，支持二者均为肿瘤成分这一假说。虽然上皮和间质均为克隆性增殖，但它们似乎有不同的克隆起源。
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