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  • Title: Quantitative lectin-histochemical 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.
    Author: Vierbuchen MJ, Fruechtnicht W, Brackrock S, Krause KT, Zienkiewicz TJ.
    Journal: Cancer; 1995 Sep 01; 76(5):727-35. PubMed ID: 8625173.
    Abstract:
    BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Sequence-specific sialylation is associated with altered biologic behavior of colorectal carcinomas.
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