Richards et al_2021_gastricCa.pdf (697.48 kB)
Development of a novel weighted ranking method for immunohistochemical quantification of a heterogeneously expressed protein in gastro-esophageal cancers
journal contributionposted on 2023-07-25, 16:49 authored by Catherine RichardsCatherine Richards, Katherine SheehanKatherine Sheehan, Elaine KayElaine Kay, Charlotta Hedner, David Borg, Joanna FayJoanna Fay, Anthony O'GradyAnthony O'Grady, Arnold HillArnold Hill, Karin Jirström, Ann HopkinsAnn Hopkins
High expression of Junctional Adhesion Molecule-A (JAM-A) has been linked with poor prognosis in several cancers, including breast cancers overexpressing the human epidermal growth factor receptor-2 (HER2). Furthermore, JAM-A expression has been linked with regulating that of HER2, and associated with the development of resistance to HER2-targeted therapies in breast cancer patients. The purpose of this study was to establish a potential relationship between JAM-A and HER2 in HER2-overexpressing gastro-esophageal (GE) cancers. Interrogation of gene expression datasets revealed that high JAM-A mRNA expression was associated with poorer survival in HER2-positive gastric cancer patients. However, high intra-tumoral heterogeneity of JAM-A protein expression was noted upon immunohistochemical scoring of a GE cancer tissue microarray (TMA), precluding a simple confirmation of any relationship between JAM-A and HER2 at protein level. However, in a test-set of 25 full-face GE cancer tissue sections, a novel weighted ranking system proved effective in capturing JAM-A intra-tumoral heterogeneity and confirming statistically sig-nificant correlations between JAM-A/HER2 expression. Given the growing importance of immuno-histochemistry in stratifying cancer patients for the receipt of new targeted therapies, this may sound a cautionary note against over-relying on cancer TMAs in biomarker discovery studies of heterogeneously expressed proteins. It also highlights a timely need to develop validated mechanisms of capturing intra-tumoral heterogeneity to aid in future biomarker/therapeutic target development for the benefit of cancer patients.
Understanding the mechanistic role and druggability of JAM-A, an emerging upstream regulator of breast cancer tumourigenic signalling, using in vitro and in vivo methodologies and a novel small molecu | Funder: Science Foundation Ireland (SFI) | Grant ID: 13/IA/1994
Breast Cancer Ireland
Health Research Board of Ireland (HRA-POR-2014-545)
CommentsThe original article is available at https://www.mdpi.com/
Published CitationRichards CE. Et al. Development of a novel weighted ranking method for immunohistochemical quantification of a heterogeneously expressed protein in gastro-esophageal cancers. Cancers (Basel). 2021;13(6):1286.
Publication Date13 March 2021
- Beaumont Hospital
- Surgical Science and Practice
- Published Version (Version of Record)