Rubin Grandis J, Melhem M F, Barnes E L, Tweardy D J
Department of Otolaryngology, University of Pittsburgh Cancer Institute, Pennsylvania, USA.
Cancer. 1996 Sep 15;78(6):1284-92. doi: 10.1002/(SICI)1097-0142(19960915)78:6<1284::AID-CNCR17>3.0.CO;2-X.
Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) mRNA are up-regulated in squamous cell carcinoma of the head and neck (SCCHN) tissues.
Immunohistochemical staining with monoclonal antibodies to TGF-alpha and EGFR was undertaken to identify the cellular origin in tissue obtained from cancer patients and controls and to determine the correlation between mRNA expression levels and two methods of immunohistochemical evaluation.
TGF-alpha protein staining occurred in the suprabasal layers and spared the basal layer of normal controls. Conversely, in histologically normal mucosa from SCCHN patients, TGF-alpha was present throughout the epithelium, including the basal layer. EGFR staining was negligible in normal mucosa from control patients without cancer and relatively increased in SCCHN tissues. Increasing staining intensity was correlated with worsening dysplasia and closer proximity to the tumor. Using computerized image analysis to quantify the intensity of immunostaining, the mean optical density (MOD) of TGF-alpha staining in histologically normal mucosa (P = 0.049) and tumors (P = 0.005) from SCCHN patients was significantly higher than in control normal mucosa from noncancer patients (1.9- and 1.7-fold, respectively). EGFR MOD was also greater in the histologically normal mucosa (P = 0.009) and tumors (P = 0.006) from SCCHN patients than in control normal mucosa (1.8- and 1.9-fold, respectively). For both TGF-alpha (P = 0.668) and EGFR (P = 0.116), the MOD was similar for both tumor and histologically normal mucosa from SCCHN patients.
TGF-alpha and EGFR protein expression is increased early in head and neck squamous cell carcinogenesis and can be quantitated by computerized image analysis of immunohistochemical staining. Altered distribution of TGF-alpha protein in histologically normal mucosa from SCCHN patients compared with control mucosa from patients without cancer suggests a switch from a paracrine to an autocrine pathway.
转化生长因子-α（TGF-α）和表皮生长因子受体（EGFR）mRNA在头颈部鳞状细胞癌（SCCHN）组织中上调。
采用针对TGF-α和EGFR的单克隆抗体进行免疫组织化学染色，以确定癌症患者和对照者组织中的细胞来源，并确定mRNA表达水平与两种免疫组织化学评估方法之间的相关性。
TGF-α蛋白染色出现在正常对照的基底上层，而基底细胞层未染色。相反，在SCCHN患者的组织学正常黏膜中，TGF-α存在于整个上皮层，包括基底细胞层。在无癌对照患者的正常黏膜中，EGFR染色可忽略不计，而在SCCHN组织中相对增加。染色强度增加与发育异常加重和肿瘤距离更近相关。使用计算机图像分析对免疫染色强度进行定量，SCCHN患者组织学正常黏膜（P = 0.049）和肿瘤（P = 0.005）中TGF-α染色的平均光密度（MOD）显著高于非癌患者的对照正常黏膜（分别为1.9倍和1.7倍）。SCCHN患者组织学正常黏膜（P = 0.009）和肿瘤（P = 0.006）中的EGFR MOD也高于对照正常黏膜（分别为1.8倍和1.9倍）。对于TGF-α（P = 0.668）和EGFR（P = 0.116），SCCHN患者肿瘤和组织学正常黏膜的MOD相似。
TGF-α和EGFR蛋白表达在头颈部鳞状细胞癌发生早期增加，可通过免疫组织化学染色的计算机图像分析进行定量。与无癌患者的对照黏膜相比，SCCHN患者组织学正常黏膜中TGF-α蛋白分布的改变提示从旁分泌途径向自分泌途径的转变。
