Digital image analysis of multiplex fluorescence IHC in colorectal cancer recognizes the prognostic value of CDX2 and its negative correlation with SOX2

Nair Lopes, Christian Holst Bergsland, Merete Bjørnslett, Teijo Pellinen, Aud Svindland, Arild Nesbakken, Raquel Almeida, Ragnhild A. Lothe, Leonor David, Jarle Bruun

Research output: Contribution to journalArticle

Abstract

Flourescence-based multiplex immunohistochemistry (mIHC) combined with multispectral imaging and digital image analysis (DIA) is a quantitative high-resolution method for determination of protein expression in tissue. We applied this method for five biomarkers (CDX2, SOX2, SOX9, E-cadherin, and β-catenin) using tissue microarrays of a Norwegian unselected series of primary colorectal cancer. The data were compared with previously obtained chromogenic IHC data of the same tissue cores, visually assessed by the Allred method. We found comparable results between the methods, although confirmed that DIA offered improved resolution to differentiate cases with high and low protein expression. However, we experienced inherent challenges with digital image analysis of membrane staining, which was better assessed visually. DIA and mIHC enabled quantitative analysis of biomarker coexpression on the same tissue section at the single-cell level, revealing a strong negative correlation between the differentiation markers CDX2 and SOX2. Both methods confirmed known prognostic associations for CDX2, but DIA improved data visualization and detection of clinicopathological and biological associations. In summary, mIHC combined with DIA is an efficient and reliable method to evaluate protein expression in tissue, here shown to recapitulate and improve detection of known clinicopathological and survival associations for the emerging biomarker CDX2, and is therefore a candidate approach to standardize CDX2 detection in pathology laboratories.

Original languageEnglish (US)
Pages (from-to)120-134
Number of pages15
JournalLaboratory Investigation
Volume100
Issue number1
DOIs
StatePublished - Jan 1 2020

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Colorectal Neoplasms
Fluorescence
Biomarkers
Immunohistochemistry
Catenins
Proteins
Differentiation Antigens
Cadherins
Pathology
Staining and Labeling
Membranes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Digital image analysis of multiplex fluorescence IHC in colorectal cancer recognizes the prognostic value of CDX2 and its negative correlation with SOX2. / Lopes, Nair; Bergsland, Christian Holst; Bjørnslett, Merete; Pellinen, Teijo; Svindland, Aud; Nesbakken, Arild; Almeida, Raquel; Lothe, Ragnhild A.; David, Leonor; Bruun, Jarle.

In: Laboratory Investigation, Vol. 100, No. 1, 01.01.2020, p. 120-134.

Research output: Contribution to journalArticle

Lopes, Nair ; Bergsland, Christian Holst ; Bjørnslett, Merete ; Pellinen, Teijo ; Svindland, Aud ; Nesbakken, Arild ; Almeida, Raquel ; Lothe, Ragnhild A. ; David, Leonor ; Bruun, Jarle. / Digital image analysis of multiplex fluorescence IHC in colorectal cancer recognizes the prognostic value of CDX2 and its negative correlation with SOX2. In: Laboratory Investigation. 2020 ; Vol. 100, No. 1. pp. 120-134.
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