Said I T, Shamsuddin A M, Sherief M A, Taleb S G, Aref W F, Kumar D
Department of Pathology, University of Maryland School of Medicine, Baltimore, USA.
Histol Histopathol. 1999 Apr;14(2):351-7. doi: 10.14670/HH-14.351.
The tumor marker, D-galactose-beta [1-3]-N-acetyl-D-galactosamine (Gal-GalNAc, also known as T-antigen) can be identified by a very simple galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with colorectal neoplasms. Gal-GalNAc is expressed in the neoplastic mucosa as well as the remote non-neoplastic mucosa. It is, however, not expressed in colonic mucosa of normal subjects. We studied the expression of Gal-GalNAc by GOS reaction, lectin reactivity and immunocytochemistry in 10 normal, .45 precancerous [5 Crohn's disease, 15 ulcerative colitis (5 without dysplasia and 10 with dysplasia), 25 tubular adenomas], and 25 adenocarcinoma cases. Normal mucosa remote from tubular adenoma and adenocarcinoma was also studied. The GOS method was compared with reactivity of the lectin jacalin and immunostaining with antibody to T antigen (Anti-Tag Ab). GOS reaction was negative in all of the 10 normal specimens. Of the 5 Crohn's disease specimens, 2 were positive and 3 negative. In the 5 ulcerative colitis cases without dysplasia, positive reaction was seen in 2 cases and negative in 3. Of the 10 cases of ulcerative colitis with dysplasia, 5 showed positivity in dysplastic areas, and 3 of these were also positive in remote non dysplastic mucosa. Twenty of 25 tubular adenomas yielded a positive reaction in the adenoma, 14 of them showing positivity also in remote mucosa; 3 cases showed a positive reaction only in remote mucosa. Of the 25 adenocarcinomas, 21 showed a positive reaction in the adenocarcinoma as well as the remote mucosa. GOS reaction was intense in well differentiated adenocarcinoma and weak in poorly differentiated adenocarcinoma. Intense reaction was also seen in the intracellular mucus of some aberrant crypts and morphologically normal crypts remote from adenocarcinoma and tubular adenoma. GOS reaction showed an overall sensitivity of 75.7% and specificity of 100% for cancer and precancerous lesions. Jacalin reactivity was slightly more sensitive (84.3%) but less specific (80%) and Tag Ab reactivity even less sensitive (50%) but as specific (100%) for neoplastic and dysplastic mucosa. We conclude that the detection of the carbohydrate moiety Gal-GalNAc varies with the technique used. Compared to other techniques, GOS reaction is extremely simple and has a high degree of sensitivity and specificity. It can be used for detection of this tumor marker in remote non-neoplastic mucosa of patients with neoplasia or at risk of developing neoplasia. It, therefore, could be used as a cost effective screening test in rectal biopsy specimens of such patients.
肿瘤标志物D-半乳糖-β[1-3]-N-乙酰-D-半乳糖胺(Gal-GalNAc,也称为T抗原)可通过一种非常简单的半乳糖氧化酶-席夫(GOS)反应在结直肠肿瘤患者的组织或直肠黏液样本中得以识别。Gal-GalNAc在肿瘤性黏膜以及远处的非肿瘤性黏膜中均有表达。然而,在正常受试者的结肠黏膜中并不表达。我们通过GOS反应、凝集素反应性和免疫细胞化学研究了10例正常、45例癌前病变[5例克罗恩病、15例溃疡性结肠炎(5例无发育异常和10例有发育异常)、25例管状腺瘤]以及25例腺癌病例中Gal-GalNAc的表达情况。同时也研究了远离管状腺瘤和腺癌的正常黏膜。将GOS方法与凝集素红豆蔻凝集素的反应性以及用T抗原抗体(抗T标签抗体)进行的免疫染色进行了比较。GOS反应在所有10例正常标本中均为阴性。在5例克罗恩病标本中,2例为阳性,3例为阴性。在5例无发育异常的溃疡性结肠炎病例中,2例呈阳性反应,3例呈阴性。在10例有发育异常的溃疡性结肠炎病例中,5例在发育异常区域呈阳性,其中3例在远处无发育异常的黏膜中也呈阳性。25例管状腺瘤中有20例在腺瘤中产生阳性反应,其中14例在远处黏膜中也呈阳性;3例仅在远处黏膜中呈阳性反应。在25例腺癌中,21例在腺癌以及远处黏膜中均呈阳性反应。GOS反应在高分化腺癌中强烈,在低分化腺癌中较弱。在一些异常隐窝以及远离腺癌和管状腺瘤的形态正常的隐窝的细胞内黏液中也可见强烈反应。GOS反应对癌症和癌前病变的总体敏感性为75.7%,特异性为100%。红豆蔻凝集素反应性稍敏感一些(84.3%),但特异性较低(80%),而抗T标签抗体反应性甚至更不敏感(50%),但对肿瘤性和发育异常的黏膜特异性相同(100%)。我们得出结论,碳水化合物部分Gal-GalNAc的检测因所使用的技术而异。与其他技术相比,GOS反应极其简单,具有高度的敏感性和特异性。它可用于检测肿瘤患者或有发生肿瘤风险患者的远处非肿瘤性黏膜中的这种肿瘤标志物。因此,它可作为此类患者直肠活检标本中一种经济有效的筛查试验。