Expression of Lewis Antigenic Determinants in Colorectal Adenocarcinomas

Abstract

Expression of type 1 and type 2 chain Lewis antigens was studied in 32 rectal adenocarcinoma specimens; the results were correlated with the patients’ Lewis phenotype and secretor status. In addition, the pattern of expression of these antigens was analyzed in adjacent and distant normal mucosa. We used an indirect immunofluorescence technique with p-phenylenediamine counterstaining (Oriol technique) and a panel of monoclonal antibodies directed against the different antigenic specificities. Normal distal colonic mucosa only expresses monofucosylated structures (Le^a and X) arising from activity of the α1–3,4-fucosyltransferase coded by the Le gene. Rectal adenocarcinomas also show Le^a and X, but also reexpress blood group antigens ABH and exhibit difucosylated determinants (Le^b and Y). The accumulation of mono- and difucosylated type 2 chain in neoplastic processes, independently of the Le and Se genes, could be due to the enzymes coded by reactivation of the H and X genes. Blood group antigens form a complex signal code, genetically regulated, which intervenes in differentiation, growth and cellular recognition processes, and which may undergo important modifications during malignant transformation. These alterations could be useful in the diagnosis and prognosis of some types of carcinoma.

Screening of enzymatic synthesis and expression of Lewis determinants in human colorectal carcinoma

“…Several authors have found no significant differences in the expression of Le y in CRC tumour tissue in comparison with healthy mucosa (40). However, our reported change in Le y expression is consistent with those of previous studies (27,28,41,42) which have justified the classical consideration of this determinant as an oncofetal antigen (43) and a premalignant biomarker of distal CRC (18,40). In this regard, it should be noted that tumour biomarkers are not only monitors for diagnosis or monitoring of patients, but represent real characteristics of cancer cells.…”

“…3), in spite of previous evidence showing a correlation between the increased expression of Le b and the Dukes' stage of each specimen (19,26). On the contrary, other studies have reported the uniform Le a distribution throughout the colon before and after the occurrence of CRC (27,28), or even its reduced expression in parallel with the appearance of colorectal malignancy (16,20). In any case, our apparent increase of a(1,2)FT activity in the tumour colonic tissue is in line with histological (29) and a(1,2)FT cDNA-transfected rat colon cell lines (30) studies, and with them we suggest that since this key enzyme acts on core 1, it could be responsible for regulating the expression of both Le a and Le b antigens, in competition with the a (1,4) FT for this common acceptor (29).…”

ABH and Lewis histo‐blood group antigens in cancer

“…57-S9, 62-64). Conversely, as compared to the normal corresponding tissues, it decreases in colon prostate and breast carcinomas (30,34,72,73). In the case of the Leb antigen, the situation is rather similar to that of the A and B antigens.…”

“…In the case of the Leb antigen, the situation is rather similar to that of the A and B antigens. Its level of expression is increased in carcinomas from the distal colon, the rectum, the thyroid and the liver (28,45,47,54,(72)(73)(74)(75), but also from the urinary bladder, while it decreases in stomach carcinomas (59,62,64). Finally, the Ley antigen has its expression strongly augmented in nearly all types of carcinomas (17, 28, 35, 40, 41, 4 3 4 5 , 48, 72, 73, [76][77][78][79][80][81] with the exception of the pancreatic and possibly endometrial carcinomas for which a decrease has been reported (58,70,7 1,82).…”

Immunohistological patterns of blood group ABO and type 1 chain (Lewis a Lewis b) and type 2 chain (H‐2, Y) antigens in normal uterine cervix

“…Blood group-related antigens (BGA) are oligosaccarides widely distributed in the body, especially in epithelial cells (1)(2)(3)(4)(5)(6). In most individuals (approximately 80%), they are also found in secretions (saliva, gastric juice); these individuals are denominated "secretors".…”