Lectins in Cervical Screening

Abstract

Cervical screening in low-resource settings remains an unmet need. Lectins are naturally occurring sugar-binding glycoproteins whose binding patterns change as cancer develops. Lectins discriminate between dysplasia and normal tissue in several precancerous conditions. We explored whether lectins could be developed for cervical screening via visual inspection. Discovery work comprised lectin histochemistry using a panel of candidate lectins on fixed-human cervix tissue (high-grade cervical intraepithelial neoplasia (CIN3, n = 20) or normal (n = 20)), followed by validation in a separate cohort (30 normal, 25 CIN1, 25 CIN3). Lectin binding was assessed visually according to staining intensity. To validate findings macroscopically, near-infra red fluorescence imaging was conducted on freshly-resected cervix (1 normal, 7 CIN3), incubated with topically applied fluorescently-labelled lectin. Fluorescence signal was compared for biopsies and whole specimens according to regions of interest, identified by the overlay of histopathology grids. Lectin histochemistry identified two lectins—wheat germ agglutinin (WGA) and Helix pomatia agglutinin (HPA)—with significantly decreased binding to CIN3 versus normal in both discovery and validation cohorts. Findings at the macroscopic level confirmed weaker WGA binding (lower signal intensity) in CIN3 vs. normal for biopsies (p = 0.0308) and within whole specimens (p = 0.0312). Our findings confirm proof-of-principle and indicate that WGA could potentially be developed further as a probe for high-grade cervical disease.

Heterogeneidade relacionada ao câncer de mama representada em miRNAs circulantes e vesiculares: resultados de ensaios de alto rendimento e prova de conceito para seleção de vesículas extracelulares derivadas de tumor

“…Normal adjacent cells show tiny and organized nuclei with a weak Jacalin staining, whereas tumor cells show an aberrant organization and variable intensities of Jacalin staining. This reflects the intratumoral heterogeneity (50-90% cells) previously described in other experiments (Figure 50D) and other studies in the literature involving lectin histochemistry [410,411].…”

Glycosylation in Cervical Cancer: New Insights and Clinical Implications

“…Two lectins, wheat germ agglutinin (WGA) and Helix pomatia agglutinin (HPA) were taken for lectin histochemistry, the staining of which was decreased in high-grade cervical intraepithelial neoplasia (CIN) relative to adjacent normal tissues in discovery and validation cohorts. Lectin staining for WGA seemed to be substantially weaker in the CIN3 area compared to the tumor-adjacent normal tissue in the specimen, as shown by more reduced fluorescence (7). A glycoprotein that contains a free amino terminus was covalently conjugated to carboxylated Luminex beads with a particular fluorescent spectral address.…”

“…It has been proposed that the a2,6-terminal sialylation and fucosylation patterns of intracellular proteins in cervical cancer are distinct from the normal cervix tissues (4). Lectins are naturally oligomeric glycoproteins characterized by the carbohydrate recognition domain with staining intensity alterations as an imaging probe for cervical cancer (7).…”