I. Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Pathol Oncol Res. 2009 Sep;15(3):445-50. doi: 10.1007/s12253-009-9155-z.
Chemotherapies are widely used in the treatment of lung cancer. However, little is known about their effect in the expression of different tissue markers. Seventeen lung cancer tissue blocks obtained by bronchoscopic biopsies together with their corresponding surgical biopsies after neoadjuvant chemotherapy were studied. They included 9 adenocarcinomas (ADC) and 8 squamous cell carcinomas (SCC). Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues to study the expression of Ki-67, p53, Bcl-2, Bax, Fas-ligand and ERCC1 (excision repair cross-complementation group 1). Out of 17 NSCLC 6 expressed proapoptotic markers and 4 expressed antiapoptotic markers, while in 7 cases the apoptotic markers did not show detectable changes after neoadjuvant chemotherapy. Six of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment. Eight bronchoscopic NSCLC tissues (6 SCC, 2 ADC) expressed ERCC1. All but one ADC became ERCC1 negative after neoadjuvant therapy. There was no newly expressed ERCC1 positive case in the surgical biopsy group. Platinum-based neoadjuvant chemotherapy had no effect on the apoptotic activity of 17 patients' tumor specimen, however, 6 of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment, in 3 cases the level of Ki-67 became decreased, while 8 cases had no detectable change of proliferation activity. The results of the present study suggest that platinum-based chemotherapy probably induces a selection of tumor cells with more aggressive phenotype, and also affects the expression of tissue marker (ERCC1) that could have predictive value.
化疗广泛用于肺癌的治疗。然而，对于它们在不同组织标志物表达中的作用知之甚少。本研究共纳入 17 例经支气管镜活检获得的肺癌组织块及其新辅助化疗后的相应手术活检标本，包括 9 例腺癌（ADC）和 8 例鳞状细胞癌（SCC）。采用福尔马林固定、石蜡包埋组织进行免疫组织化学染色，研究 Ki-67、p53、Bcl-2、Bax、Fas 配体和 ERCC1（切除修复交叉互补组 1）的表达。在 17 例 NSCLC 中，有 6 例表达促凋亡标志物，有 4 例表达抗凋亡标志物，而在 7 例中，凋亡标志物在新辅助化疗后未显示出可检测到的变化。在新辅助治疗后，17 例支气管镜 NSCLC 中有 6 例表达 Ki-67 水平增加。8 例支气管镜 NSCLC 组织（6 例 SCC，2 例 ADC）表达 ERCC1。除 1 例 ADC 外，所有患者在新辅助治疗后均转为 ERCC1 阴性。在手术活检组中，没有新的 ERCC1 阳性病例。基于铂的新辅助化疗对 17 例患者肿瘤标本的凋亡活性没有影响，然而，在新辅助治疗后，17 例支气管镜 NSCLC 中有 6 例表达 Ki-67 水平增加，在 3 例中 Ki-67 水平降低，而 8 例增殖活性无明显变化。本研究结果表明，基于铂的化疗可能诱导具有侵袭性表型的肿瘤细胞选择，并且还影响组织标志物（ERCC1）的表达，该标志物可能具有预测价值。
