Ibrahim S O, Vasstrand E N, Liavaag P G, Johannessen A C, Lillehaug J R
Department of Odontology-Oral Pathology and Forensic Odontology, University of Bergen, Norway.
Anticancer Res. 1997 Nov-Dec;17(6D):4539-46.
The exact role of oncogenes and proto-oncogenes in the development of squamous cell carcinoma of the head and neck (SCCHN) is still debatable. The expression of the c-erbB-2, c-erbB-3 and c-erbB-4 members of the epidermal growth factor receptor family was examined in 16 fresh frozen tissue specimens of SCCHN using avidin-biotin complex immunohistochemistry, with monoclonal and/or polyclonal antibodies directed against each. Eight fresh frozen tissue specimens of normal oral mucosa were included as controls. Of the SCCHN examined, mixed membrane/cytoplasmic staining (moderate to intense) of c-erbB-2 was found in 14/16 cases (88%). When present in the specimen, immunopositive staining of c-erbB-2 was seen in some of the oral surface epithelial cell layers (basal, intermediate and/or superficial) as well as the tumour islands. Weak cytoplasmic staining of c-erbB-3 and c-erbB-4 was found in 13/16 (81%) and 11/16 (69%) cases respectively. When present in the specimen, c-erbB-3 and cerbB-4 immunopositive staining was seen in some of the oral surface epithelial cell layers (basal, intermediate and/or superficial) as well as the tumour islands. For the positive carcinomas for c-erbB-2, c-erbB-3 and c-erbB-4, the epithelium located near the carcinomas showed weak mixed membrane/cytoplasmic staining of c-erbB-2 in 5/14 cases (36%), weak cytoplasmic staining of c-erbB-3 in 7/13 cases (54%) and of c-erbB-4 in 3/11 cases (27%). All the normal control oral mucosa showed the same pattern of staining for c-erbB-2, c-erbB-3 and c-erbB-4 found in the epithelium located near the carcinomas. Only expression of c-erbB-2 was found to correlate with the increase in the tumour stage, while co-expression of c-erbB-2, c-erbB-3 and c-erbB-4 was found to correlate with the patient survival time in 25% of the carcinomas examined. The present study shows that a) expression of c-erbB-2, but not c-erbB-3 and c-erbB-4 correlates with the increase of the tumour stage b) co-expression of c-erbB-2, c-erbB-3 and c-erbB4 correlates with decreased survival time in some of the cases of SCCHN, but not the majority c) co-expression of the c-erbB family in normal oral mucosa as well as in the carcinoma may question whether the increased tendency for development of the disease is due to co-expression of c-erbB proto-oncogenes in head and neck lesions.
癌基因和原癌基因在头颈部鳞状细胞癌（SCCHN）发生发展中的确切作用仍存在争议。采用抗生物素蛋白-生物素复合物免疫组织化学方法，使用针对表皮生长因子受体家族的c-erbB-2、c-erbB-3和c-erbB-4成员的单克隆和/或多克隆抗体，检测了16例新鲜冷冻的头颈部鳞状细胞癌组织标本。纳入8例正常口腔黏膜新鲜冷冻组织标本作为对照。在所检测的头颈部鳞状细胞癌中，14/16例（88%）发现c-erbB-2呈混合性膜/细胞质染色（中度至强阳性）。当标本中存在时，在部分口腔表面上皮细胞层（基底、中间和/或表层）以及肿瘤岛中可见c-erbB-2免疫阳性染色。分别在13/16例（81%）和11/16例（69%）中发现c-erbB-3和c-erbB-4呈弱阳性细胞质染色。当标本中存在时，在部分口腔表面上皮细胞层（基底、中间和/或表层）以及肿瘤岛中可见c-erbB-3和c-erbB-4免疫阳性染色。对于c-erbB-2、c-erbB-3和c-erbB-4阳性的癌，在靠近癌的上皮中，5/14例（36%）显示c-erbB-2呈弱阳性混合性膜/细胞质染色，7/13例（54%）显示c-erbB-3呈弱阳性细胞质染色，3/11例（27%）显示c-erbB-4呈弱阳性细胞质染色。所有正常对照口腔黏膜显示出与靠近癌的上皮中相同的c-erbB-2、c-erbB-3和c-erbB-4染色模式。仅发现c-erbB-2的表达与肿瘤分期增加相关，而在25%的所检测癌中，c-erbB-2、c-erbB-3和c-erbB-4的共表达与患者生存时间相关。本研究表明：a）c-erbB-2的表达而非c-erbB-3和c-erbB-4的表达与肿瘤分期增加相关；b）在部分头颈部鳞状细胞癌病例中，c-erbB-2、c-erbB-3和c-erbB-4的共表达与生存时间缩短相关，但并非大多数病例；c）c-erbB家族在正常口腔黏膜以及癌中的共表达可能使人质疑该疾病发生发展倾向增加是否归因于头颈部病变中原癌基因c-erbB的共表达。
