Quantitative lectinhistochemical and immunohistochemical studies on the occurrence of alpha(2,3)- and alpha(2,6)-linked sialic acid residues in colorectal carcinomas. Relation to clinicopathologic features

Abstract

Enhanced sialylation has been considered important for the metastatic growth of colorectal carcinomas. Using sequence- and sialic acid-specific lectins and a monoclonal antibody, the tumor-associated expression of alpha(2,3)- and alpha(2,6)-sialylated oligosaccharides was investigated. The study was designed to examine whether a random increase of sialylation or the expression of oligosaccharides carrying distinct sialic acid residues affect the biology of colorectal carcinomas. Using computerized image analysis, formalin fixed and paraffin wax embedded specimens from 152 primary colorectal carcinomas were subjected to a quantitative analysis of the occurrence of sialoglycoconjugates detected by the maackia amurensis agglutinin (MAA: specific for alpha(2,3)-linked sialic acid residues), sambucus nigra agglutinin (SNA: specific for alpha(2,6)-linked sialic acid residues), and the monoclonal antibody B72.3 (MAB B72.3: specific for alpha(2,6)-N-acetyl-galactosamine-1-O-Ser/Thre). The data obtained by quantitating lectin/immunohistochemistry were related to morphologic and clinical parameters. Alpha(2,3)-linked sialic acid residues increased from Stage I to Stage II tumors but decreased in advanced carcinomas. Alpha(2,6)-sialylated glycoconjugates did not show any association with local tumor growth (depth of invasion). However, metastatic tumor growth was accompanied by a significant increase of alpha(2,6)-sialylated carbohydrate sequences. Univariate survival analysis revealed that the expression of SNA- and MAB B72.3-defined reactivity displayed an inverse relation to 5-year survival. Although more advanced tumor stage was associated with poor 5-year survival, tumors below the cutoff points for SNA- and MAB B72.3-defined reactivity indicated a better prognosis than the neoplasms above the cutoff points. In contrast, the expression of alpha(2,3)-linked sialic acid residues as detected by MAA had no significant effect on survival. Multivariate regression analysis revealed that SNA-reactivity, followed by tumor stage and the MAB B72.3-defined antigen reactivity were independent prognostic variables predicting overall survival, whereas MAA-reactivity, sex, age, histologic differentiation, and tumor grade had no independent prognostic value. The simultaneous expression of both sialyl-Tn- and SNA-reactivity determined tumors of high risk patients within the different tumor stages. Sequence-specific sialylation is associated with altered biologic behavior of colorectal carcinomas.