Sanders D S, Bruton R, Darnton S J, Casson A G, Hanson I, Williams H K, Jankowski J
Department of Histopathology, Queen Elizabeth Hospital, Birmingham, UK.
Int J Cancer. 1998 Dec 18;79(6):573-9. doi: 10.1002/(sici)1097-0215(19981218)79:6<573::aid-ijc4>3.0.co;2-h.
Maintenance of an adhesive function for cadherins requires appropriate membranous cellular expression and intact cadherin-catenin complexes. In normal squamous mucosa of the oesophagus there is membranous co-expression of E- and P-cadherin (E-cad, P-cad) in the basal compartment, whereas suprabasal stratification is associated with preservation of E-cad expression but loss of P-cad. Immunohistochemical staining of squamous dysplasia/carcinoma in situ shows a striking increase in the proportion of cells within the epithelial compartment showing co-expression of E- and P-cad with strong appropriate membranous expression of beta and gamma catenin. Strong membranous co-expression of E- and P-cad and beta catenin is seen on keratinocytes at the periphery of islands of invasive better-differentiated squamous carcinoma with keratinisation, mimicking normal mucosa. Beta catenin may be phosphorylated with implied loss of cadherin binding. Membranous cadherin and catenin expression is significantly down-regulated in poorly differentiated squamous carcinoma. No beta catenin mutations were demonstrated in squamous carcinomas following DNA extraction and sequencing, nor was any nuclear cadherin seen. Changes in cadherin-catenin complexes with cellular phenotype is well demonstrated in spindle cell carcinomas with a shift of cadherin expression from membranous to cytoplasmic between the epithelioid and spindle cell components of the tumour and with loss of expression in the sarcomatoid elements. In conclusion, we demonstrate an increased expression of P-cadherin early in tumourigenesis with loss of cadherin-catenin complexes in poorly differentiated invasive carcinomas. Cadherin/catenin expression may govern both the phenotype and biology of oesophageal squamous carcinomas.
钙黏蛋白黏附功能的维持需要适当的细胞膜细胞表达和完整的钙黏蛋白-连环蛋白复合物。在正常食管鳞状黏膜中，E-钙黏蛋白（E-cad）和P-钙黏蛋白（P-cad）在基底部分呈膜共表达，而上皮上层的分层与E-钙黏蛋白表达的保留但P-钙黏蛋白的缺失相关。鳞状发育异常/原位癌的免疫组织化学染色显示，在上皮部分中，显示E-钙黏蛋白和P-钙黏蛋白共表达且β和γ连环蛋白有强且适当膜表达的细胞比例显著增加。在具有角化的浸润性高分化鳞状癌岛周边的角质形成细胞上可见E-钙黏蛋白、P-钙黏蛋白和β连环蛋白的强膜共表达，类似于正常黏膜。β连环蛋白可能被磷酸化，这意味着钙黏蛋白结合丧失。在低分化鳞状癌中，膜钙黏蛋白和连环蛋白的表达显著下调。DNA提取和测序后，未在鳞状细胞癌中发现β连环蛋白突变，也未见到任何核钙黏蛋白。在梭形细胞癌中，钙黏蛋白-连环蛋白复合物随细胞表型的变化得到了很好的证明，肿瘤的上皮样和梭形细胞成分之间钙黏蛋白表达从膜性转变为细胞质，肉瘤样成分中表达缺失。总之，我们证明在肿瘤发生早期P-钙黏蛋白表达增加，而在低分化浸润性癌中钙黏蛋白-连环蛋白复合物缺失。钙黏蛋白/连环蛋白表达可能决定食管鳞状细胞癌的表型和生物学特性。
