LaPoint Randi J A, Bourne Patricia A, Wang Hanlin L, Xu Haodong
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Elmwood 601, Rochester, NY 14642, USA.
Appl Immunohistochem Mol Morphol. 2007 Dec;15(4):401-6. doi: 10.1097/01.pai.0000213153.41440.7d.
It has been shown that tyrosine kinase oncoprotein c-kit and antiapoptotic molecule bcl-2 are overexpressed in several types of malignancy, including small cell carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung. Whether these 2 molecules are coexpressed in lung neuroendocrine tumors has not been investigated. Here, we analyzed immunohistochemical results to determine expression and coexpression patterns of c-kit and bcl-2 in the spectrum of lung neuroendocrine tumors. Using a polyclonal antibody against c-kit and a monoclonal antibody against bcl-2, our data demonstrated that all 7 cases (100%) of SCLC included in this study were positive for both c-kit and bcl-2. Among 14 LCNECs, 7 (50%) stained positive for c-kit and 9 (64%) for bcl-2. All cases of high grade neuroendocrine carcinomas (SCLCs and LCNECs) that showed positive staining for c-kit coexpressed bcl-2. In contrast, all typical and atypical carcinoids (TC and AC) were negative for c-kit, and only 1 of 16 (6.3%) TCs and 1 of 6 (16.7%) ACs stained positive for bcl-2. These results indicate a progressive increase in the frequency of c-kit and bcl-2 expression and coexpression, from carcinoid tumors (TC and AC) to LCNEC and to SCLC. High grade neuroendocrine carcinomas are more likely to coexpress c-kit and bcl-2 when compared with carcinoid tumors. The high frequency of coexpression of these 2 molecules in high grade neuroendocrine carcinomas of the lung suggests that they may be involved in the carcinogenic pathway, given their important roles in carcinogenesis. Therapeutic targeting on both c-kit and bcl-2 molecules might be beneficial in the management of patients with high grade neuroendocrine carcinomas of the lung in the future.
研究表明，酪氨酸激酶癌蛋白c-kit和抗凋亡分子bcl-2在包括肺小细胞癌（SCLC）和大细胞神经内分泌癌（LCNEC）在内的多种恶性肿瘤中均有过表达。这两种分子在肺神经内分泌肿瘤中是否共表达尚未得到研究。在此，我们分析免疫组化结果，以确定c-kit和bcl-2在肺神经内分泌肿瘤谱系中的表达及共表达模式。使用抗c-kit多克隆抗体和抗bcl-2单克隆抗体，我们的数据表明，本研究纳入的所有7例（100%）SCLC的c-kit和bcl-2均呈阳性。在14例LCNEC中，7例（50%）c-kit染色阳性，9例（64%）bcl-2染色阳性。所有c-kit染色阳性的高级别神经内分泌癌（SCLC和LCNEC）病例均共表达bcl-2。相比之下，所有典型和非典型类癌（TC和AC）的c-kit均为阴性，16例TC中仅1例（6.3%）和6例AC中仅1例（16.7%）bcl-2染色阳性。这些结果表明，从类癌肿瘤（TC和AC）到LCNEC再到SCLC，c-kit和bcl-2表达及共表达的频率呈逐渐增加趋势。与类癌肿瘤相比，高级别神经内分泌癌更可能共表达c-kit和bcl-2。这两种分子在肺高级别神经内分泌癌中共表达的高频率表明，鉴于它们在致癌过程中的重要作用，它们可能参与了致癌途径。未来，针对c-kit和bcl-2分子的治疗靶点可能对肺高级别神经内分泌癌患者的管理有益。
