Yamashita Y, Chung Y S, Horie R, Kannagi R, Sowa M
First Department of Surgery, Osaka City University Medical School, Japan.
J Natl Cancer Inst. 1995 Mar 15;87(6):441-6. doi: 10.1093/jnci/87.6.441.
Mucins are high-molecular-weight glycoproteins produced by both normal and cancer cells. However, in cancer cells, abnormal mucins are synthesized and potentially can be used as markers for the development and progression of certain malignancies. In a previous study, we reported the production of a new monoclonal antibody directed against a mucin antigen termed F1 alpha, an O-linked oligosaccharide similar to sialyl Tn and Thomsen-Friedenreich (T) antigens, that has not been previously detected in human cancers. F1 alpha is expressed in a high percentage (80.2%; 89/111) of gastric cancers.
In the present study, we compared the expression of F1 alpha with that of sialyl Tn and T antigens in human gastric cancer tissues to determine how differences in the expression of these cancer-associated antigens correlated with the biological properties of cancer cells.
A total of 141 cases of gastric cancer were studied. Sections of formalin-fixed, paraffin-embedded tissue were immunostained for F1 alpha, sialyl Tn, and T antigens. The relationship between the expression of these antigens and the patient's clinicopathologic characteristics was studied. The chi-square test (two-sided) was used for statistical analyses.
F1 alpha was expressed in a high percentage of the cases of early to advanced cancers, irrespective of the degree of malignant progression. The rate of expression of sialyl Tn antigen in early carcinoma was low, but it increased significantly as depth of invasion increased (P < .05) and was significantly higher in patients with hepatic or lymph node metastasis than in those without such metastasis (P < .01). Expression of T antigen significantly increased with depth of invasion (P < .01) and was significantly higher in patients with hepatic metastasis (P < .05), lymph node metastasis (P < .05), or peritoneal dissemination (P < .01) than in those without such metastasis or dissemination. In consecutive sections of the same specimen, the sites of staining for F1 alpha and sialyl Tn antigens seldom coincided. In many cases, F1 alpha staining was predominant, but the sialyl Tn-dominant region tended to increase as gastric cancer progressed. Regions of T-antigen staining were usually circumscribed by those of F1 alpha staining.
Our findings indicate that the expression of F1 alpha begins almost at the same time as does carcinogenesis in gastric epithelial cells. Moreover, in association with progression of gastric carcinoma, synthetic pathways for sialyl Tn antigen and T antigen probably are activated independently.
黏蛋白是由正常细胞和癌细胞产生的高分子量糖蛋白。然而，在癌细胞中，会合成异常黏蛋白，其有可能用作某些恶性肿瘤发生和发展的标志物。在先前的一项研究中，我们报道了一种针对黏蛋白抗原F1α产生的新型单克隆抗体，F1α是一种与唾液酸化Tn及汤姆森-弗里德赖希（T）抗原相似的O-连接寡糖，此前在人类癌症中尚未检测到。F1α在高比例（80.2%；89/111）的胃癌中表达。
在本研究中，我们比较了F1α与唾液酸化Tn及T抗原在人胃癌组织中的表达情况，以确定这些癌症相关抗原表达的差异与癌细胞生物学特性之间的相关性。
共研究了141例胃癌病例。对福尔马林固定、石蜡包埋组织切片进行F1α、唾液酸化Tn及T抗原的免疫染色。研究了这些抗原的表达与患者临床病理特征之间的关系。采用卡方检验（双侧）进行统计分析。
无论恶性进展程度如何，F1α在早期至晚期癌症病例中的表达比例都很高。唾液酸化Tn抗原在早期癌中的表达率较低，但随着浸润深度增加其表达显著升高（P < 0.05），且在有肝转移或淋巴结转移的患者中显著高于无此类转移的患者（P < 0.01）。T抗原的表达随着浸润深度增加而显著升高（P < 0.01），且在有肝转移（P < 0.05）、淋巴结转移（P < 0.05）或腹膜播散（P < 0.01）的患者中显著高于无此类转移或播散的患者。在同一样本的连续切片中，F1α和唾液酸化Tn抗原的染色部位很少重合。在许多病例中，F1α染色占主导，但随着胃癌进展，唾液酸化Tn占主导的区域有增加趋势。T抗原染色区域通常被F1α染色区域所包围。
我们的研究结果表明，F1α的表达几乎与胃上皮细胞癌变同时开始。此外，随着胃癌进展，唾液酸化Tn抗原和T抗原的合成途径可能是独立激活的。
