Zhu Li-Qin, Diao Lu-Ming, Chen De-Ji, Li Hong-Gang, Liu Xuan, Zou Zu-Yu, Li Bei-Yun, Wang Min, Liu Ming-Qiu
Department of Pathology, Wuhan University, Wuhan, Hubei, PR China.
Ai Zheng. 2003 Jun;22(6):571-4.
BACKGROUND & OBJECTIVE: Abnormality of FHIT gene has been proved to be frequent in certain malignant tumors closely related to environmental oncogenic factors, such as lung cancer. Foreign scholars have begun to explore the relationship between FHIT gene and other tumor suppressor genes, which are implicated in the pathogenesis of lung cancer. This study was designed to investigate the relationship between hMSH(2) and FHIT protein expression and to explore the correlation of hMSH(2) and FHIT protein expression with clinicopathologic features of lung cancer.
Immunohistochemical analysis of hMSH(2) and FHIT protein expression in 40 lung cancer cases and 15 adjacent non-cancer lung tissues was performed; the positive rates of FHIT and hMSH(2) proteins were measured by image analysis system.
(1)The positive rates of FHIT and hMSH(2) proteins were 58.2% and 45.8% respectively in lung cancer tissues compared with 89.1% and 65.3% in non-cancer lung tissues. The expression levels of FHIT and hMSH(2) proteins were significantly lower in lung cancer tissues than that in non-cancer lung tissues (P< 0.01). (2)Reduced expression levels of both proteins were significantly related to tumor histology. The positive rate of the FHIT protein was 52.2% in squamous cell carcinoma compared with 63.4% in adenocarcinomas(P< 0.01), whereas the positive rate of the hMSH(2) protein was 35.6% in adenocarcinomas compared with 53.2% in squamous cell carcinoma(P< 0.01). (3)A correlation between FHIT reduced expression and lymph node metastasis was observed(P< 0.01). The positive rate of the FHIT protein was 54.1% in lung cancer tissues with metastasis compared with 60.5% in lung cancer tissues without metastasis. No association was found between hMSH(2) reduced expression and nodal metastasis(P >0.05). (4)Loss of FHIT protein correlated significantly with lasting and heavy smoking(P< 0.01). The positive rate of the FHIT protein was 53.1% in smoking group compared with 66.1% in non-smoking group. The reduction of hMSH(2) expression was not associated with smoking(P >0.05). (5)An inverse correlation was found between hMSH(2) reduced expression and FHIT protein loss (P< 0.01, RR=-0.54).
FHIT gene may be a negative regulatory gene of hMSH(2) gene, and play an important role in the inactivation mechanism of hMSH(2) gene.
已证实FHIT基因异常在某些与环境致癌因素密切相关的恶性肿瘤（如肺癌）中较为常见。国外学者已开始探索FHIT基因与其他参与肺癌发病机制的肿瘤抑制基因之间的关系。本研究旨在探讨hMSH(2)与FHIT蛋白表达之间的关系，并探讨hMSH(2)和FHIT蛋白表达与肺癌临床病理特征的相关性。
对40例肺癌病例和15例癌旁非癌肺组织进行hMSH(2)和FHIT蛋白表达的免疫组织化学分析；采用图像分析系统测定FHIT和hMSH(2)蛋白的阳性率。
(1)肺癌组织中FHIT和hMSH(2)蛋白的阳性率分别为58.2%和45.8%，而在非癌肺组织中分别为89.1%和65.3%。肺癌组织中FHIT和hMSH(2)蛋白的表达水平明显低于非癌肺组织（P<0.01）。(2)两种蛋白表达水平降低均与肿瘤组织学显著相关。鳞状细胞癌中FHIT蛋白的阳性率为52.2%，腺癌中为63.4%（P<0.01），而腺癌中hMSH(2)蛋白的阳性率为35.6%，鳞状细胞癌中为53.2%（P<0.01）。(3)观察到FHIT表达降低与淋巴结转移之间存在相关性（P<0.01）。有转移的肺癌组织中FHIT蛋白的阳性率为54.1%，无转移的肺癌组织中为60.5%。未发现hMSH(2)表达降低与淋巴结转移之间存在关联（P>0.05）。(4)FHIT蛋白缺失与长期大量吸烟显著相关（P<0.01）。吸烟组中FHIT蛋白的阳性率为53.1%，非吸烟组中为66.1%。hMSH(2)表达降低与吸烟无关（P>0.05）。(5)发现hMSH(2)表达降低与FHIT蛋白缺失呈负相关（P<0.01，RR=-0.54）。
FHIT基因可能是hMSH(2)基因的负调控基因，在hMSH(2)基因的失活机制中起重要作用。
