Development of a novel weighted ranking method for immunohistochemical quantification of a heterogeneously expressed protein in gastro-esophageal cancers

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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 ...

2021-03-13
MDPI AG,2021
12 s.

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LIBRIS-ID:oai:lup.lub.lu.se:fe1c78fc-d355-4f8c-9b15-91fb9c2c5b26
https://lup.lub.lu.se/record/fe1c78fc-d355-4f8c-9b15-91fb9c2c5b26URI
https://doi.org/10.3390/cancers13061286DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Cancer
Gastro-esophageal cancer
HER2
Immunohistochemistry
Intra-tumoral heterogeneity
JAM-A
Tissue microarray
Tumor

Added entries (persons, corporate bodies, meetings, titles ...)

Sheehan, Katherine M.Beaumont Hospital, Dublin (author)
Kay, Elaine W.Beaumont Hospital, Dublin (author)
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)
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)
Fay, JoannaBeaumont Hospital, Dublin (author)
O’grady, AnthonyBeaumont Hospital, Dublin (author)
Hill, Arnold D.K.Beaumont Hospital, Dublin (author)
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)
Hopkins, Ann M.Beaumont Hospital, Dublin (author)
Beaumont Hospital, DublinTerapeutisk patologi (creator_code:org_t)

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In:Cancers: MDPI AG13:62072-6694

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By the author/editor: Richards, Cathy ...; Sheehan, Katheri ...; Kay, Elaine W.; Hedner, Charlott ...; Borg, David; Fay, Joanna; show more...; O’grady, Anthony; Hill, Arnold D.K ...; Jirström, Karin; Hopkins, Ann M.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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