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非小细胞肺癌中Bax、bcl-2和c-kit的表达及其对预后的影响。

Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis.

作者信息

Yaren A, Oztop I, Kargi A, Ulukus C, Onen A, Sanli A, Binicier O, Yilmaz U, Alakavuklar M

机构信息

Department of Iternal Medicine, Division of Hematology-Oncology, University of Pamukkale, Denizli, Turkey.

出版信息

Int J Clin Pract. 2006 Jun;60(6):675-82. doi: 10.1111/j.1368-5031.2006.00742.x.

DOI:10.1111/j.1368-5031.2006.00742.x
PMID:16805752
Abstract

In non-small-cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2 genes which are important in apoptosis and c-kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC) methods. IHC evaluation was done by the semichantitative method according to the distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%) stage IIIB and three cases (4.4%) were stage IV patients. Their histological subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma, 28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma (two patients) and large-cell carcinoma (three patients). The positive immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%, respectively. The positive immune staining rates for c-kit in whole group, squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%, respectively. We didn't find any correlation with Bax, bcl-2 and c-kit expressions and clinicopathological parameters such as age, tumour size, lymph node involvement, smoking, stage of the disease, response to radiotherapy and chemotherapy. Results are interpreted according to survival; bax and bcl-2 expressions were not so effective both in whole group and histologically subgrouped patients. C-kit expression was also found not related with survival in whole group whereas found as a bad prognostic factor in patients with squamous cell carcinoma. These findings could indicate that the expression of apoptotic pathway markers and c-kit may have a role in the prognosis of early stage NSCLC, especially with squamous cell carcinoma subtype.

摘要

在非小细胞肺癌(NSCLC)中,疾病分期仍然是最重要的预后因素。除分期外,人们还研究了许多生物标志物和其他预后因素,以确定它们对肺癌预后的影响。在本研究中,我们旨在评估在细胞凋亡中起重要作用的Bax和bcl-2基因以及作为酪氨酸激酶跨膜受体的c-kit的表达情况,并探寻它们对治疗方式的反应及对生存的影响。采用免疫组织化学(IHC)方法,用特异性的Bax、bcl-2和c-kit染料对69例NSCLC病例的病理样本进行染色。根据染色的分布和强度,采用半定量方法进行IHC评估。69例患者中,12例(17.4%)为I期,28例(40.5%)为II期,17例(24.6%)为IIIA期,9例(13.1%)为IIIB期,3例(4.4%)为IV期。其组织学亚型如下:69例中,36例(52.2%)为鳞状细胞癌,28例(40.6%)为腺癌,5例(7.2%)为腺鳞癌(2例)和大细胞癌(3例)。全组、鳞状细胞癌组和腺癌组中Bax和bcl-2的阳性免疫染色率分别为40.6%/36.2%、55.6/69.4%和25.0/0.0%。全组、鳞状细胞癌组和腺癌组中c-kit的阳性免疫染色率分别为7.2%、5.6%和7.1%。我们未发现Bax、bcl-2和c-kit的表达与年龄、肿瘤大小、淋巴结受累情况、吸烟、疾病分期、放疗和化疗反应等临床病理参数之间存在任何相关性。根据生存情况对结果进行解读;Bax和bcl-2的表达在全组和组织学亚组患者中均未显示出明显效果。在全组中,c-kit的表达也与生存无关,而在鳞状细胞癌患者中,c-kit表达是一个不良预后因素。这些发现可能表明,凋亡途径标志物和c-kit的表达可能在早期NSCLC尤其是鳞状细胞癌亚型的预后中起作用。

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