Ex-vivo study of lectins in cervical screening
Research type
Research Study
Full title
An ex-vivo study using molecular imaging of lectins to detect high-grade cervical intraepithelial neoplasia
IRAS ID
176899
Contact name
Anita W W Lim
Contact email
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
Cervical cancer has become relatively rare in many countries due to screening and treatment of pre-cursor disease (dysplasia). However, reading smears is a subjective activity which has never successfully been transferred to low-income countries. A potential solution is visual inspection (having a nurse look at the cervix). Acetic acid or Lugol’s iodine is dabbed on the cervix and areas of dysplasia change colour. Unfortunately the results are highly subjective and can lead to unnecessary treatments. A visual inspection tool that is better than what is currently used could have a major impact on cervical cancer in developing countries.
Lectins are naturally occurring proteins which bind to sugars on the surface of cells. As the pattern of sugars alter with dysplasia, so does the ability of lectins to bind. In laboratory studies using fixed human cervical tissue we have identified two lectins which displayed significantly weaker binding in CIN3 vs normal tissue. These are wheat germ agglutinin (WGA)(an extract of wheat) and helix pomatia agglutinin (HPA)(an extract of garden snails). We would like to confirm our findings in freshly removed human cervical tissue. We plan to apply WGA or HPA to tissue that has been excised routinely for diagnostic or treatment purposes. Lectins will be labelled so they light up when exposed to the correct light. Biopsies will be taken from areas with high binding (ie light up the most) and compared to biopsies taken from areas with low binding (ie light up the least) to see if dysplasia can be identified by different binding patterns.
This is a small pilot study to see if our results remain effective in freshly removed tissue. The results will inform the decision on whether or not to move on to a proof-of-principle study in living patients.
Summary of Results
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.
REC name
Yorkshire & The Humber - Bradford Leeds Research Ethics Committee
REC reference
15/YH/0371
Date of REC Opinion
12 Aug 2015
REC opinion
Favourable Opinion