Baldus S E, Hanisch F G, Kotlarek G M, Zirbes T K, Thiele J, Isenberg J, Karsten U R, Devine P L, Dienes H P
Institute of Pathology, University of Cologne, Germany.
Cancer. 1998 Mar 15;82(6):1019-27. doi: 10.1002/(sici)1097-0142(19980315)82:6<1019::aid-cncr3>3.0.co;2-9.
Controversial findings have been reported regarding the expression of the Thomsen-Friedenreich (TF) antigen in colorectal neoplasms when different monoclonal antibodies (MoAbs) have been used. Moreover, there is no information available regarding the carrier protein(s) of this antigen.
Forty-five colorectal adenomas and 48 carcinomas were studied by avidin-biotin complex-peroxidase immunohistochemistry. The immunohistochemistry employed the MoAb BW835, which was reactive to a carrier specific and site specific TF antigen on MUC1 mucin, as well as reference antibodies directed to MUC1 (HMFG2) or MUC2 core peptides (4F1) and directed to TF antigen irrespective of its carrier (A78-G/A7, peanut agglutinin). To evaluate the coexpression of different epitopes by the same antigen, sandwich enzyme-linked immunoadsorbent assays were performed.
Although MUC1 peptide antigen and MUC1-bound TF antigen were not detectable in normal or transitional mucosa surrounding colorectal neoplasms, expression of these antigens in adenomas accompanied the development of high grade dysplasia. By contrast, MUC2 expression detected by the MoAb 4F1 was inversely correlated with the progression of the adenoma-carcinoma sequence. In well- and moderately differentiated colorectal carcinomas, the neo-expressed TF antigen is predominantly bound to MUC1. This feature could be demonstrated by antigen coexpression using peptide and the TF antigen specific MoAbs. However, in mucinous carcinomas exhibiting a weak MUC1 peptide expression in most specimens, the presence of TF antigen on the MUC2 peptide core cannot be ruled out.
TF antigen is strongly coexpressed with MUC1 mucin peptide core in the colorectal adenoma-carcinoma sequence, resulting in well- and moderately differentiated carcinomas. Only in mucinous carcinomas may it be coexpressed with MUC2 antigen.
当使用不同的单克隆抗体(MoAb)时,关于结直肠肿瘤中汤姆森-弗里德赖希(TF)抗原的表达报道存在争议。此外,关于该抗原的载体蛋白尚无可用信息。
采用抗生物素蛋白-生物素复合物-过氧化物酶免疫组织化学法研究了45例结直肠腺瘤和48例癌。免疫组织化学使用了对MUC1粘蛋白上载体特异性和位点特异性TF抗原具有反应性的MoAb BW835,以及针对MUC1(HMFG2)或MUC2核心肽(4F1)的参考抗体,和针对TF抗原而不考虑其载体的抗体(A78-G/A7,花生凝集素)。为了评估同一抗原不同表位的共表达,进行了夹心酶联免疫吸附试验。
虽然在结直肠肿瘤周围的正常或移行黏膜中未检测到MUC1肽抗原和与MUC1结合的TF抗原,但这些抗原在腺瘤中的表达伴随着高级别发育异常的发展。相比之下,MoAb 4F1检测到的MUC2表达与腺瘤-癌序列的进展呈负相关。在高分化和中分化结直肠癌中,新表达的TF抗原主要与MUC1结合。使用肽和TF抗原特异性MoAb进行抗原共表达可证明这一特征。然而,在大多数标本中MUC1肽表达较弱的黏液癌中,不能排除MUC2肽核心上存在TF抗原。
在结直肠腺瘤-癌序列中,TF抗原与MUC1粘蛋白肽核心强烈共表达,导致高分化和中分化癌。仅在黏液癌中它可能与MUC2抗原共表达。