Department of Pathology, University of Chicago Medical Center, Chicago, IL, USA.
Arch Pathol Lab Med. 2010 Nov;134(11):1702-5. doi: 10.1043/2009-0664-OAR1.1.
c-Met is important in the pathogenesis, invasion, and spread of several forms of lung cancer, and multiple c-Met inhibitors are undergoing clinical trials. PAX5 has been shown to upregulate c-Met in small cell lung carcinoma (SCLC), and coinhibiting PAX5 and c-Met had a synergic effect in killing tumor cells. Paxillin is a downstream target of activated c-Met, and its activation leads to enhanced cell motility and tumor spread. The expression patterns of these functionally related proteins have not, to our knowledge, been systemically studied in neuroendocrine tumors of the lung.
To investigate the expression patterns of PAX5, paxillin, c-Met, and phosphorylated c-Met in 4 categories of pulmonary neuroendocrine tumors.
Tissue microarrays of 38 typical carcinoids, 6 atypical carcinoids, 34 SCLCs, and 11 large cell neuroendocrine carcinomas were studied with immunohistochemistry.
Most of the 4 tumor types expressed c-Met, phosphorylated c-Met, and paxillin. PAX5 was frequently expressed in atypical carcinoids, SCLCs, and large cell neuroendocrine carcinomas but tended to be negative in typical carcinoids. Coexpression of PAX5 with c-Met or phosphorylated c-Met was present in most of the atypical carcinoids, SCLCs, and large cell neuroendocrine carcinomas. Significant correlation between PAX5 and paxillin was detected in SCLCs and large cell neuroendocrine carcinomas but not in carcinoid tumors.
The frequent coexpression of PAX5 with c-Met or phosphorylated c-Met in intermediate-grade and high-grade neuroendocrine tumors supports the therapeutic strategy of coinhibiting these proteins. The discrepancy between high-grade and low-grade neuroendocrine tumors in PAX5/paxillin expression correlation may be due to the different underlying molecular genetics of these tumors.
c-Met 在多种肺癌的发病机制、侵袭和转移中起着重要作用，多种 c-Met 抑制剂正在进行临床试验。PAX5 已被证明可上调小细胞肺癌（SCLC）中的 c-Met，而同时抑制 PAX5 和 c-Met 对杀伤肿瘤细胞具有协同作用。桩蛋白是激活的 c-Met 的下游靶标，其激活导致细胞迁移和肿瘤扩散增强。据我们所知，这些功能相关蛋白在肺部神经内分泌肿瘤中的表达模式尚未系统研究过。
研究 PAX5、桩蛋白、c-Met 和磷酸化 c-Met 在 4 种肺神经内分泌肿瘤中的表达模式。
用免疫组织化学法研究了 38 例典型类癌、6 例非典型类癌、34 例 SCLC 和 11 例大细胞神经内分泌癌的组织微阵列。
4 种肿瘤类型均表达 c-Met、磷酸化 c-Met 和桩蛋白。PAX5 在非典型类癌、SCLC 和大细胞神经内分泌癌中常表达，但在典型类癌中往往为阴性。PAX5 与 c-Met 或磷酸化 c-Met 的共表达存在于大多数非典型类癌、SCLC 和大细胞神经内分泌癌中。在 SCLC 和大细胞神经内分泌癌中检测到 PAX5 与桩蛋白之间存在显著相关性，但在类癌肿瘤中未检测到。
中高级别神经内分泌肿瘤中 PAX5 与 c-Met 或磷酸化 c-Met 的频繁共表达支持联合抑制这些蛋白的治疗策略。高级别和低级别神经内分泌肿瘤在 PAX5/桩蛋白表达相关性上的差异可能是由于这些肿瘤的不同潜在分子遗传学所致。
