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Development of a no...
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Richards, Cathy E.Beaumont Hospital, Dublin
(author)
Development of a novel weighted ranking method for immunohistochemical quantification of a heterogeneously expressed protein in gastro-esophageal cancers
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-03-13
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MDPI AG,2021
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12 s.
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:fe1c78fc-d355-4f8c-9b15-91fb9c2c5b26
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https://lup.lub.lu.se/record/fe1c78fc-d355-4f8c-9b15-91fb9c2c5b26URI
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https://doi.org/10.3390/cancers13061286DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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.
Subject headings and genre
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Sheehan, Katherine M.Beaumont Hospital, Dublin
(author)
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Kay, Elaine W.Beaumont Hospital, Dublin
(author)
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Hedner, CharlottaLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-cah
(author)
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Borg, DavidLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-dbo
(author)
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Fay, JoannaBeaumont Hospital, Dublin
(author)
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O’grady, AnthonyBeaumont Hospital, Dublin
(author)
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Hill, Arnold D.K.Beaumont Hospital, Dublin
(author)
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Jirström, KarinLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)pat-kji
(author)
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Hopkins, Ann M.Beaumont Hospital, Dublin
(author)
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Beaumont Hospital, DublinTerapeutisk patologi
(creator_code:org_t)
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In:Cancers: MDPI AG13:62072-6694
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Kay, Elaine W.
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Hedner, Charlott ...
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Borg, David
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Fay, Joanna
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O’grady, Anthony
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- MEDICAL AND HEALTH SCIENCES
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and Clinical Medicin ...
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Cancers
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Lund University