Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions
Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions
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DOI：
10.1097/01.mp.0000062656.60581.aa
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发表时间：
2003-04-01
期刊：
影响因子：
7.5
通讯作者：
Argani, P
中科院分区：
文献类型：
--
作者：
Parwani, AV;Geradts, J;Argani, P
胆囊癌是高度致命的肿瘤。相对而言，人们对这些肿瘤的遗传异常知之甚少，特别是在肿瘤进展的时间方面。作者通过免疫组织化学方法评估了5例非侵袭性发育不良和33例浸润性胆囊癌（6例小细胞癌，27例非小细胞癌，其中16例伴有原位癌成分）p16、p53、Dpc4和pRB肿瘤抑制基因蛋白产物的表达。肿瘤也被评估是否存在活化的K-ras癌基因突变。75%的非小细胞胆囊癌表现出p16表达的缺失，而63%的p53积累了高水平。Dpc4和pRB表达缺失较少见，分别在19%和4%的肿瘤中可见。30%的肿瘤含有活化的K-ras突变。相比之下，100%的胆囊小细胞癌表现出pRB/p16通路失活；67%的人表达pRB缺失，33%的人表达p16缺失。83%的小细胞癌积累了高水平的p53，而没有发现Dpc4表达缺失和激活K-ras突变。在15个可评估的原位成分中，13个具有与侵入性成分相同的改变。p16和p53失活发生在大多数非小细胞胆囊癌中。Dpc4失活和K-ras突变发生在少数病例中。pRB缺失在非小细胞胆囊癌中并不常见，但几乎所有的小细胞癌都通过视网膜母细胞瘤蛋白缺失使p16/pRB通路失活。值得注意的是，所有这些改变都发生在原位癌水平。
Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing hi neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6 small cell carcinomas, 27 non-small cell carcinomas, of which 16 were accompanied by an in situ carcinoma component) for expression of the protein products of the p16, p53, Dpc4, and pRB tumor suppressor genes by immunohistochemistry. Neoplasms were also evaluated for the presence of activating K-ras oncogene mutations. Seventy-five percent of non-small cell gallbladder carcinomas demonstrated loss of p16 expression, whereas 63% accumulated high levels of p53. Loss of Dpc4 and pRB expression was less frequent, seen in 19% and 4% of the neoplasms, respectively. Thirty percent of neoplasms harbored activating K-ras mutations. In contrast, 100% of the small cell carcinomas of the gallbladder demonstrated inactivation of the pRB/p16 pathway; 67% showed loss of pRB expression, and the other 33% lost p16 expression. Eighty-three percent of small cell carcinomas accumulated high levels of p53, whereas loss of Dpc4 expression and activating K-ras mutations were not found. Among 15 evaluable in situ components, 13 harbored the same alterations found in the invasive component. Inactivation of p 16 and p53 occur in the majority of non-small cell gallbladder carcinomas. Dpc4 inactivation and K-ras mutations occur in a significant minority of cases. pRB loss is uncommon in non-small cell gallbladder carcinoma, but virtually all small cell carcinomas inactivate the p16/pRB pathway, usually by retinoblastoma protein loss. It is noteworthy that all of these alterations occur at the level of carcinoma in situ.