Nomura Hitomi, Uzawa Katsuhiro, Yamano Yukio, Fushimi Kazuaki, Nakashima Dai, Kouzu Yukinao, Kasamatsu Atsushi, Ogawara Katsunori, Shiiba Masashi, Bukawa Hiroki, Yokoe Hidetaka, Tanzawa Hideki
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
J Cancer Res Clin Oncol. 2009 Jul;135(7):943-9. doi: 10.1007/s00432-008-0530-z. Epub 2008 Dec 20.
To determine the potential involvement of ANXA1 in oral squamous-cell carcinoma (OSCC), we evaluated the ANXA1 protein expression in oral premalignant lesions (OPLs) and OSCCs and correlated the results with clinicopathologic variables.
Matched normal and tumour specimens of 44 primary OSCCs and 28 OPLs were analyzed for ANXA1 subcellular localization and protein expression level by immunohistochemistry (IHC). Correlations between ANXA1-IHC staining scores of OSCCs and clinicopathologic features were evaluated by Fisher's exact test.
Markedly down-regulation of ANXA1 protein expression was identified on the plasma membrane of epithelial cells in OSCCs (P < 0.001) and OPLs (P = 0.001) compared with normal counterparts. Moreover, loss of plasma membranous ANXA1 expression was significantly correlated with the poorly differentiated status of OSCC cells (P = 0.012).
Our findings suggest that loss of ANXA1 is frequent and early event during oral carcinogenesis and that ANXA1 could contribute to maintaining epithelial differentiation in OSCC.
为了确定膜联蛋白A1(ANXA1)在口腔鳞状细胞癌(OSCC)中的潜在作用,我们评估了口腔癌前病变(OPL)和OSCC中ANXA1蛋白的表达情况,并将结果与临床病理变量进行关联分析。
采用免疫组织化学(IHC)方法,对44例原发性OSCC和28例OPL的配对正常组织和肿瘤组织标本进行分析,以确定ANXA1的亚细胞定位和蛋白表达水平。通过Fisher精确检验评估OSCC的ANXA1-IHC染色评分与临床病理特征之间的相关性。
与正常组织相比,OSCC(P < 0.001)和OPL(P = 0.001)上皮细胞膜上的ANXA1蛋白表达明显下调。此外,细胞膜上ANXA1表达的缺失与OSCC细胞的低分化状态显著相关(P = 0.012)。
我们的研究结果表明,ANXA1的缺失是口腔致癌过程中常见的早期事件,并且ANXA1可能有助于维持OSCC中的上皮分化。