Department of Anatomical Pathology, Hospital A.C. Camargo, 01509-900 São Paulo, Brazil.
Hum Pathol. 2011 Oct;42(10):1484-90. doi: 10.1016/j.humpath.2010.12.015. Epub 2011 Apr 14.
Sonic hedgehog signaling is important for human development, and aberrant regulation of this pathway can result in the development of tumors. The aim of this study was to examine the expression of sonic hedgehog signaling molecules in oral squamous cell carcinoma. By quantitative real-time polymerase chain reaction, the expression of SHH, SMO, PTCH-1, and GLI-1 was analyzed in 30 oral squamous cell carcinoma cases and 8 samples of nonneoplastic oral mucosa and associated to clinical pathologic features. The expression of β-catenin, cyclin D1, Wnt-1, and Egfr was evaluated by immunohistochemistry in 26 available cases of oral squamous cell carcinoma. Normal oral mucosa from healthy individuals was negative for all genes that were evaluated. SHH, PTCH-1, SMO, and GLI-1 were not expressed in nonneoplastic oral mucosa, and low levels of GLI-1 were observed in nonneoplastic oral mucosa that was adjacent to the tumor. All oral squamous cell carcinoma cases expressed high levels of PTCH-1, SMO, and GLI-1 and were devoid of SHH. The expression of SMO was associated with clinical stage (P = .022) and a borderline association in cervical lymph node metastasis (P = .053). PTCH-1 expression showed a strong correlation with SMO (rs = 0.64; P < .001) and GL-1 (rs = 0.70; P < .001); SMO and GLI-1 also correlated with each other (rs, 0.55; P < .001). All proteins evaluated were expressed as cyclin D1 (92% of samples), β-catenin (73%), Egfr (46%), or Wnt-1 (32%). Our data demonstrate that sonic hedgehog signaling is activated in oral squamous cell carcinoma and suggest that this pathway mediates its tumorigenesis.
声波刺猬信号对于人类的发育非常重要，而该通路的异常调节可能导致肿瘤的发生。本研究旨在探讨声波刺猬信号分子在口腔鳞状细胞癌中的表达。通过定量实时聚合酶链反应，分析了 30 例口腔鳞状细胞癌和 8 例非肿瘤性口腔黏膜组织中 SHH、SMO、PTCH-1 和 GLI-1 的表达，并与临床病理特征相关联。在 26 例可获得的口腔鳞状细胞癌病例中，通过免疫组织化学评估了β-连环蛋白、细胞周期蛋白 D1、Wnt-1 和 EGFR 的表达。正常的口腔黏膜组织对所有评估的基因均呈阴性。非肿瘤性口腔黏膜组织中不表达 SHH、PTCH-1、SMO 和 GLI-1，肿瘤旁的非肿瘤性口腔黏膜组织中仅观察到低水平的 GLI-1。所有口腔鳞状细胞癌病例均高表达 PTCH-1、SMO 和 GLI-1，而不表达 SHH。SMO 的表达与临床分期（P =.022）和颈淋巴结转移（P =.053）呈弱相关。PTCH-1 表达与 SMO（rs = 0.64；P <.001）和 GL-1（rs = 0.70；P <.001）呈强相关；SMO 和 GLI-1 之间也存在相关性（rs = 0.55；P <.001）。所有评估的蛋白均表达为 cyclin D1（92%的样本）、β-连环蛋白（73%）、EGFR（46%）或 Wnt-1（32%）。我们的数据表明，声波刺猬信号在口腔鳞状细胞癌中被激活，并提示该通路介导其肿瘤发生。
