【作者】 姚健；

【导师】 邵国光；

【作者基本信息】 吉林大学 ， 外科学， 2014， 博士

【摘要】 肺癌是发病率和死亡率增长最快，对人群健康和生命威胁最大的恶性肿瘤之一。伴随着人们体检意识的日益提高，以及高端螺旋CT在基层医院的普及，越来越多的早期肺癌患者被从无症状的健康人群中筛查出来，尤其是一些双肺多发肺结节（≥2个）的病人越来越多的出现在临床医师的视野内。对于这类病人，一旦其中一个结节被诊断为恶性病变，那么剩余的结节性病变多数会被诊断为肺内转移癌，而其中一部分同期多发肺癌的患者会因此丧失临床治愈的机会。因此，对于肺内多发恶性结节的病人，能否在诊断早期明确其是否为肺内转移癌，对其后续治疗就显得尤为重要。肿瘤的转移是一个复杂的，多因素参与调控的过程。多种基因参与其中，结肠癌转移相关基因1（MACC1）是这其中备受关注的一个。MACC1于2009年由stein第一次报道出来，它通过对HGF/c-Met信号通路的调控引起肿瘤的转移和侵袭。MACC1和c-Met高表达与多种肿瘤侵润转移有关，这点已在结肠癌、肝癌、胃癌、肾盂癌、肺癌等多种肿瘤中均有报道。但在肺部转移癌组织中是否存在高表达，其表达程度是否和肺原发癌组织中的表达程度存在明显差异，国内外尚无此类报道。通过此项研究我们可以明确肺部转移癌组织中的MACC1和c-Met的表达程度；并反向通过MACC1和c-Met的高表达鉴别肺部结节是否为转移癌，从而指导同期肺多发恶性肿瘤的具体临床治疗方法。目的：探讨结肠癌转移相关基因1（MACC1）及肝细胞生长因子受体（c-Met）在同期多发肺癌、原发肺癌、肺内转移癌中的表达及其临床意义。方法：采用免疫组织化学染色法和Western印迹检测法检测8例同期双原发肺癌（其中4例有新鲜冰冻标本）、20例原发肺癌及20例肺内转移癌组织中MACC1和c-Met的表达情况，并结合临床情况进行分析。结果：在所有标本中MACC1的高表达和c-Met的高表达呈正相关（P＜0.01），免疫组化法：在所有标本中MACC1的高表达和c-Met的高表达呈正相关（P＜0.01），免疫组化染色后，MACC１蛋白的表达主要位于组织细胞的胞质及包膜，在肺部转移癌的强阳性表达率为60%（12/20）；在多原发肺癌强阳性表达率为12.5%（2/16）；在原发肺癌的强阳性表达率为15.5%（3/20）；在癌旁组织中强阳性表达率为10.0%（2/20）。进行统计学检验，MACC1在肺部转移癌的强阳性表达与在癌旁组织中的表达上的差异有统计学意义（P＝0.031），在多原发肺癌及原发肺癌中的强阳性表达与癌旁组织中的表达无统计学差异。C-Met蛋白主要定位于组织的包膜。在肺部转移癌的强阳性表达率为55.0%（11/20）；在多原发肺癌的强阳性表达率为12.5%（2/16）；在原发肺癌的强阳性表达率为15.0%（3/20）；在癌旁组织中强阳性表达率为15.0%（3/20）。进行统计学检验，C-Met在肺部转移癌的强阳性表达与在癌旁组织中的表达上的差异有统计学意义（P＝0.033），在多原发肺癌及原发肺癌中的强阳性表达与癌旁组织中的表达无统计学差异。在所有肺内转移癌标本中MACC1和C-Met均强阳性表达率为50%（10/20）。蛋白印迹法检测：肺部转移癌组织、同期多原发肺癌组织、原发肺癌组织MACC１蛋白的相对表达量分别为（1.03±0.97）、（0.59±0.57）、（0.47±0.41），其中肺部转移癌MACC１蛋白表达量显著高于多原发肺癌和原发肺癌组织（P＝0.031、P＝0.042），多原发肺癌组织MACC１蛋白的表达量与原发肺癌组织之间差异没有统计学意义（P＝0.452）。结论：MACC1和c-Met的高表达与肺内转移癌密切相关，联合检测可作为判断肺内可疑结节是否为转移癌的重要指标。更多还原

【Abstract】 Objective：To investigate the expressions of metastasis-associated in colon cancer1(MACC1) and hepatocyte growth factor receptor(c-Met) in synchronous multipleprimary lung carcinoma, and to demonstrate their relationship with the metastasis oflung.Methods:The expression of MACC1and c–Met in8cases of the same period (4caseswith fresh frozen specimen) of double primary lung cancer,20cases of primary lungcancer and20cases of pulmonary metastatic carcinoma were detected byimmunohistochemical staining and Western imprinting method, and based on whichclinical situations are analyzed.Results:High expression of MACC1was positively correlated with high expression of c–Met in all specimens(P <0.01).Immunohistochemical method: The expression ofMACC1protein is mainly located in cytoplasm and capsular tissue cells, the strongpositive expression rate of pulmonary metastatic carcinoma was60.0%(12/20), theexpression rate of multiple primary lung cancer is12.5%(2/16), the expression rate ofprimary lung cancer is15.5%(3/20)，the expression rate of pericarcinoma tissues is10.0%(2/20). The strong positive expression rate of pulmonary metastatic carcinomawas significantly higher than that of pericarcinoma tissues (P=0.031). The strongpositive expression rate of multiple primary lung cancer and primary lung cancer werenot significantly higher than that of pericarcinoma tissues. C-Met protein mainlylocate in tissue of coating, the strong positive expression rate of pulmonary metastaticcarcinoma was55.0%(11/20), the expression rate of multiple primary lung cancer is12.5%(2/16), the expression rate of primary lung cancer is15.0%(3/20), the expression rate of pericarcinoma tissues is10.0%(2/20). The strong positiveexpression rate of pulmonary metastatic carcinoma was significantly higher than thatof pericarcinoma tissues (P=0.033). The strong positive expression rate of multipleprimary lung cancer and primary lung cancer were not significantly higher than that ofpericarcinoma tissues.Western imprinting method:The relative gray value of MACC1protein was (1.03+0.97),(0.59-0.57),(0.47-0.41), in lung metastatic carcinoma tissues, and multiple primary lung cancertissues and primary lung cancer tissues. The relative gray value of MACC1protein inlung metastatic carcinoma tissues was significantly higher than that in multipleprimary lung cancer(P=0.031), and that in primary lung cancer tissues(P=0.042).The relative gray value of MACC1protein in multiple primary lung cancer was notsignificant difference with that in primary lung cancer tissues P=0.452).Conclusion:The high expression of MACC1protein and c–Met protein may play animportant role in the metastasis of lung cancer. The combined detection will haveimportant clinical significance to diagnose whether the multiple lung node is themetastasis node of lung cancer.更多还原