Wakabayashi M, Shiro T, Seki T, Nakagawa T, Itoh T, Imamura M, Shiozaki Y, Inoue K, Okamura A
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Cancer. 1995 Jun 15;75(12):2827-35. doi: 10.1002/1097-0142(19950615)75:12<2827::aid-cncr2820751207>3.0.co;2-z.
The altered expression of the Lewis blood group-related antigens during malignant transformation can be used clinically as a tumor marker or as a prognostic indicator. The Lewis Y (LeY) antigen, which is one of the Type 2 human blood group-related antigens, also is thought to behave as an oncodevelopmental cancer-associated antigen. In this study, the authors examined the association between human LeY antigen expression and the clinicopathologic features of HCC, including its proliferative activity.
Forty-six histologically confirmed cases of HCC were studied retrospectively. Liver biopsy specimens from the main tumor of each case were obtained under ultrasonic guidance before treatment was initiated. The formalin fixed, paraffin embedded serial sections were immunostained using a modification of the avidin-biotin-peroxidase complex method, with a primary monoclonal antibody (MoAb) directed against the LeY antigen (BM-1/JIMRO). The relationship between LeY antigen expression and the HCC's proliferative activity was analyzed similarly by immunohistochemical methods using a primary MoAb directed against the Ki-67 antigen (MIB 1). In addition, to clarify the relationship between LeY antigen expression and the histologic heterogeneity within HCC, seven cases of surgically resected HCC also were immunostained.
The LeY antigen was detected on the membrane and in the cytoplasm of the cancer cells. Of the 46 HCC cases, 20 (43.5%) expressed the LeY antigen in the tumor cells. There was no correlation between LeY antigen expression and the maximum tumor dimension or the Stage. However, the incidence of LeY antigen-positive cases in poorly differentiated HCCs was found to be significantly higher than that in well or moderately differentiated HCCs (P < 0.01). In resected HCC cases, LeY antigen expression within HCC nodules was frequently greater in the less differentiated tumor than in adjacent differentiated tumor. Moreover, the incidence of LeY antigen expression in alpha-fetoprotein (AFP)-positive (AFP > or = 200 ng/ml) HCC cases was significantly higher than that in AFP-negative (AFP < 200 ng/ml) HCC cases (P < 0.05). Furthermore, the mean value of the Ki-67 labeling index in LeY antigen-positive HCC cases (25.2 +/- 11.3%) was significantly higher than that in LeY antigen-negative HCC cases (9.4 +/- 4.1%) (P < 0.001).
These results suggest that LeY antigen expression correlated closely to the dedifferentiation and proliferative activity of HCC.
恶性转化过程中Lewis血型相关抗原表达的改变可在临床上用作肿瘤标志物或预后指标。Lewis Y（LeY）抗原是人类2型血型相关抗原之一，也被认为是一种肿瘤发生相关的癌相关抗原。在本研究中，作者检测了人类LeY抗原表达与肝癌临床病理特征之间的关联，包括其增殖活性。
回顾性研究46例经组织学确诊的肝癌病例。在开始治疗前，于超声引导下获取每例患者主要肿瘤的肝活检标本。将福尔马林固定、石蜡包埋的连续切片采用抗生物素蛋白-生物素-过氧化物酶复合物法的改良方法进行免疫染色，使用针对LeY抗原的一抗单克隆抗体（MoAb）（BM-1/JIMRO）。使用针对Ki-67抗原的一抗MoAb（MIB 1），通过免疫组化方法类似地分析LeY抗原表达与肝癌增殖活性之间的关系。此外，为阐明LeY抗原表达与肝癌组织学异质性之间的关系，对7例手术切除的肝癌病例也进行了免疫染色。
在癌细胞的细胞膜和细胞质中检测到LeY抗原。在46例肝癌病例中，20例（43.5%）肿瘤细胞表达LeY抗原。LeY抗原表达与肿瘤最大直径或分期之间无相关性。然而，发现低分化肝癌中LeY抗原阳性病例的发生率显著高于高分化或中分化肝癌（P < 0.01）。在切除的肝癌病例中，肝癌结节内LeY抗原表达在低分化肿瘤中通常高于相邻的分化肿瘤。此外，甲胎蛋白（AFP）阳性（AFP≥200 ng/ml）肝癌病例中LeY抗原表达的发生率显著高于AFP阴性（AFP < 200 ng/ml）肝癌病例（P < 0.05）。此外，LeY抗原阳性肝癌病例中Ki-67标记指数的平均值（25.2±11.3%）显著高于LeY抗原阴性肝癌病例（9.4±4.1%）（P < 0.001）。
这些结果表明LeY抗原表达与肝癌的去分化和增殖活性密切相关。
