دورية أكاديمية
Development of a Novel Weighted Ranking Method for Immunohistochemical Quantification of a Heterogeneously Expressed Protein in Gastro-Esophageal Cancers.
العنوان: | Development of a Novel Weighted Ranking Method for Immunohistochemical Quantification of a Heterogeneously Expressed Protein in Gastro-Esophageal Cancers. |
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المؤلفون: | Richards, Cathy E, Sheehan, Katherine M, Kay, Elaine W, Hedner, Charlotta, Borg, David, Fay, Joanna, O'Grady, Anthony, Hill, Arnold D K, Jirström, Karin, Hopkins, Ann M |
المصدر: | Cancers ; 13 ; 6 ; Ireland ; Switzerland |
سنة النشر: | 2021 |
المجموعة: | Lenus - Irish Health Publications Archive (HSE - Health Service Executive) |
مصطلحات موضوعية: | HER2, JAM-A, CANCER, gastro-esophageal cancer, immunohistochemistry, intra-tumoral heterogeneity, tissue microarray, tumor |
الوصف: | 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 significant correlations between JAM-A/HER2 expression. Given the growing importance of immunohistochemistry 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. ; peer-review |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 2072-6694 |
العلاقة: | http://hdl.handle.net/10147/631797Test; Cancers |
DOI: | 10.3390/cancers13061286 |
الإتاحة: | https://doi.org/10.3390/cancers13061286Test http://hdl.handle.net/10147/631797Test |
رقم الانضمام: | edsbas.F743AEC7 |
قاعدة البيانات: | BASE |
تدمد: | 20726694 |
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DOI: | 10.3390/cancers13061286 |