Ambrosch P, Schlott T, Hilmes D, Ruschenburg I
Department of Otorhinolaryngology, University of Goettingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany.
Virchows Arch. 2001 Apr;438(4):343-9. doi: 10.1007/s004280000368.
The progression potential of preinvasive epithelial lesions is usually evaluated by assessing the degree of histologic dysplasia. We examined p16, retinoblastoma protein (pRb), and proliferating cell nuclear antigen (PCNA) immunophenotypes in 57 cases of previously untreated squamous cell carcinoma (SCC) of the upper digestive tract and in the neighboring normal and dysplastic epithelia. Tissue samples were examined for homozygous deletion of exon 2 of the p16 gene using polymerase chain reaction (PCR) analysis. The PCNA index increased with increasing grade of dysplasia. The pRb protein was expressed in 89% of the samples of SCCs and in the neighboring dysplasias and carcinoma in situ (CIS). In cases with a lack of pRb expression, corresponding preinvasive lesions were also negative. Lack of p16 expression was found in 82% of SCCs. The prevalence of p16 expression decreased with increasing grade of dysplasia. Molecular analysis of the p16 gene showed homozygous deletion in 37% of SCCs, 33% of CIS, and 15% of the samples of normal epithelia. Our data indicate that inactivation of p16 may play an important role in early head and neck carcinogenesis, whereas the mutation of Rb may be an infrequent event. The p16 immunophenotype might be a biomarker for an increased risk of progression in squamous dysplasia.
通常通过评估组织学发育异常程度来判断浸润前上皮病变的进展潜能。我们检测了57例未经治疗的上消化道鳞状细胞癌（SCC）及其邻近正常和发育异常上皮组织中的p16、视网膜母细胞瘤蛋白（pRb）和增殖细胞核抗原（PCNA）免疫表型。采用聚合酶链反应（PCR）分析检测组织样本中p16基因第2外显子的纯合缺失情况。PCNA指数随发育异常程度的增加而升高。pRb蛋白在89%的SCC样本、邻近发育异常组织及原位癌（CIS）中表达。在缺乏pRb表达的病例中，相应的浸润前病变也呈阴性。82%的SCC存在p16表达缺失。p16表达的发生率随发育异常程度的增加而降低。对p16基因的分子分析显示，37%的SCC、33%的CIS和15%的正常上皮组织样本存在纯合缺失。我们的数据表明，p16失活可能在头颈部早期癌变中起重要作用，而Rb突变可能是罕见事件。p16免疫表型可能是鳞状发育异常进展风险增加的生物标志物。
