Shen Bin, Li Dawei, Dong Pin, Gao Shang
Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, China.
Ann Otol Rhinol Laryngol. 2011 Dec;120(12):820-7. doi: 10.1177/000348941112001208.
Two prominent and well-characterized representatives of adenosine triphosphate-binding cassette (ABC) transporter - breast cancer resistance protein (BCRP or ABCG2) and P-glycoprotein (P-gp or ABCB1) - are known to be membrane transporters associated with multidrug resistance. The aim of this study was to explore the correlation between ABC transporter expression and the clinicopathologic characteristics, proliferative index, and apoptotic index and their prognostic value in laryngeal squamous cell carcinoma (LSCC).
Paraffin sections of 98 human LSCC specimens were investigated with immunohistochemical techniques. The relationship between ABCG2 and ABCB1 expression and clinicopathologic parameters, proliferative activities, and apoptotic activities and their prognostic value in patients' overall survival rate were subsequently analyzed.
Immunohistochemical analysis revealed positive expression of ABCG2 and ABCB1 in 52.0% and 41.8% of patients, respectively. There was a positive correlation between ABCG2 expression and ABCB1 expression. The presence of these two proteins was significantly related to clinical stage, lymph node metastasis, and overall survival in LSCC. Interestingly, up-regulation of ABCG2 expression was found to be associated with increased proliferation, but that of ABCB1 was not. Up-regulation of both ABCG2 expression and ABCB1 expression was associated with decreased apoptosis.
The results of this study revealed that the presence of ABCG2 and/or ABCB1 is predictive for malignant progression and is an independent prognostic factor in LSCC. The mechanism of ABC transporters may contribute to chemotherapy resistance by promoting proliferation and/or suppressing apoptosis.
三磷酸腺苷结合盒(ABC)转运蛋白的两个著名且特征明确的代表——乳腺癌耐药蛋白(BCRP或ABCG2)和P-糖蛋白(P-gp或ABCB1)——是已知的与多药耐药相关的膜转运蛋白。本研究的目的是探讨ABC转运蛋白表达与喉鳞状细胞癌(LSCC)临床病理特征、增殖指数和凋亡指数之间的相关性及其预后价值。
采用免疫组化技术对98例人LSCC标本的石蜡切片进行研究。随后分析ABCG2和ABCB1表达与临床病理参数、增殖活性和凋亡活性之间的关系及其对患者总生存率的预后价值。
免疫组化分析显示,ABCG2和ABCB1的阳性表达分别在52.0%和41.8%的患者中出现。ABCG2表达与ABCB1表达呈正相关。这两种蛋白的存在与LSCC的临床分期、淋巴结转移和总生存率显著相关。有趣的是,发现ABCG2表达上调与增殖增加有关,但ABCB1表达上调则不然。ABCG2表达和ABCB1表达上调均与凋亡减少有关。
本研究结果表明,ABCG2和/或ABCB1的存在可预测恶性进展,是LSCC的独立预后因素。ABC转运蛋白的机制可能通过促进增殖和/或抑制凋亡导致化疗耐药。