Morohara Koji, Tajima Yusuke, Nakao Kentaro, Nishino Nobukazu, Aoki Shigeo, Kato Masanori, Sakamoto Masaaki, Yamazaki Kimiyasu, Kaetsu Tsutomu, Suzuki Satoshi, Tsunoda Akira, Tachikawa Tetsuhiko, Kusano Mitsuo
Department of Surgery, Division of General and Gastroenterological Surgery, Showa University, School of Medicine, Tokyo, Japan.
J Cancer Res Clin Oncol. 2006 Jun;132(6):363-75. doi: 10.1007/s00432-005-0062-8. Epub 2006 Jan 31.
Gastric and intestinal phenotypic cell markers are widely expressed in gastric carcinomas, irrespective of their histological type. In the present study, the relations between the phenotypic marker expression of the tumour, histological findings, expression of cell adhesion molecules, and the chromosomal changes in gastric differentiated-type carcinomas were examined. The phenotypic marker expression of the tumour was determined by the combination of the expression of the human gastric mucin (HGM), MUC6, MUC2 and CD10, and was evaluated in comparison with the expression of cell adhesion molecules, such as E-cadherin and beta-catenin, and chromosomal changes by comparative genomic hybridization (CGH) in 34 gastric differentiated-type carcinomas. Tumours were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of staining for HGM, MUC6, MUC2, and CD10. G-phenotype tumours were significantly associated with a higher incidence of differentiated-type tumours mixed with undifferentiated-type component, compared with GI- and I-phenotype tumours (88.9 vs 33.3%, P=0.0498 and 88.9 vs 42.9%, P=0.0397; respectively). HGM-positive tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with HGM-negative tumours (66.7 vs 21.1%, P=0.0135). GI-phenotype tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with I-phenotype tumours (77.8 vs 21.4%, P=0.0131). HGM-negative tumours were significantly associated with higher frequencies of the gains of 19q13.2 and 19q13.3, compared with HGM-positive tumours (57.9 vs 20.0%, P=0.0382 and 63.2 vs 13.3%, P=0.0051; respectively). MUC6-positive tumours were significantly associated with higher frequencies of the gains of 20q13.2, compared with MUC6-negative tumours (71.4 vs 30.0%, P=0.0349). MUC2-positive tumours were significantly associated with the gain of 19p13.3, compared with MUC2-negative tumours (41.2 vs 5.9%, P=0.0391). I-phenotype tumours were significantly associated with higher frequencies of gains of 5p15.2 and 13q33-34, compared with G-phenotype tumours (66.7 vs 0%, P=0.0481, each) and also associated with higher frequencies of gain of 7p21, compared with GI-phenotype tumours (66.7 vs 0%, P=0.0481). Our present results show that gastric differentiated-type carcinomas have different characteristics according to the phenotypic marker expression of the tumour in terms of histological findings, E-cadherin expression and pattern of chromosomal changes.
胃和肠表型细胞标志物在胃癌中广泛表达,无论其组织学类型如何。在本研究中,我们检测了胃分化型癌中肿瘤的表型标志物表达、组织学表现、细胞黏附分子表达与染色体变化之间的关系。通过人胃黏液素(HGM)、MUC6、MUC2和CD10的表达组合来确定肿瘤的表型标志物表达,并与细胞黏附分子(如E-钙黏蛋白和β-连环蛋白)的表达以及34例胃分化型癌中通过比较基因组杂交(CGH)检测的染色体变化进行比较评估。根据HGM、MUC6、MUC2和CD10染色的免疫阳性情况,将肿瘤分为胃型(G-)、胃和肠混合型(GI-)、肠型(I-)或未分类型(UC-)表型。与GI型和I型表型肿瘤相比,G型表型肿瘤与混合有未分化型成分的分化型肿瘤的更高发生率显著相关(分别为88.9%对33.3%,P = 0.0498;88.9%对42.9%,P = 0.0397)。与HGM阴性肿瘤相比,HGM阳性肿瘤与E-钙黏蛋白异常表达的肿瘤的更高发生率显著相关(66.7%对21.1%,P = 0.0135)。与I型表型肿瘤相比,GI型表型肿瘤与E-钙黏蛋白异常表达的肿瘤的更高发生率显著相关(77.8%对21.4%,P = 0.0131)。与HGM阳性肿瘤相比,HGM阴性肿瘤与19q13.2和19q13.3扩增的更高频率显著相关(分别为57.9%对20.0%,P = 0.0382;63.2%对13.3%,P = 0.0051)。与MUC6阴性肿瘤相比,MUC6阳性肿瘤与20q13.2扩增的更高频率显著相关(71.4%对30.0%,P = 0.0349)。与MUC2阴性肿瘤相比,MUC2阳性肿瘤与19p13.3扩增显著相关(41.2%对5.9%,P = 0.0391)。与G型表型肿瘤相比,I型表型肿瘤与5p15.2和13q33 - 34扩增的更高频率显著相关(均为66.7%对0%,P = 0.0481),并且与GI型表型肿瘤相比,也与7p21扩增的更高频率相关(66.7%对0%,P = 0.0481)。我们目前的结果表明,胃分化型癌根据肿瘤的表型标志物表达在组织学表现、E-钙黏蛋白表达和染色体变化模式方面具有不同的特征。