Combined epithelial marker analysis of tumour budding in stage II colorectal cancer

Khadija Slik, Sami Blom, Riku Turkki, Katja Välimäki, Samu Kurki, Harri Mustonen, Caj Haglund, Olli Carpén, Olli Kallioniemi, Eija Korkeila, Jari Sundström, Teijo Pellinen

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Tumour budding predicts survival of stage II colorectal cancer (CRC) and has been suggested to be associated with epithelial-to-mesenchymal transition (EMT). However, the underlying molecular changes of tumour budding remain poorly understood. Here, we performed multiplex immunohistochemistry (mIHC) to phenotypically profile tumours using known EMT-associated markers: E-cadherin (adherence junctions), integrin beta 4 (ITGB4; basement membrane), ZO-1 (tight junctions), and pan-cytokeratin. A subpopulation of patients showed high ITGB4 expression in tumour buds, and this coincided with a switch of ITGB4 localisation from the basal membrane of intact epithelium to the cytoplasm of budding cells. Digital image analysis demonstrated that tumour budding with high ITGB4 expression in tissue microarray (TMA) cores correlated with tumour budding assessed from haematoxylin and eosin (H&E) whole sections and independently predicted poor disease-specific survival in two independent stage II CRC cohorts (hazard ratio [HR] = 4.50 (95% confidence interval [CI] = 1.50-13.5), n = 232; HR = 3.52 (95% CI = 1.30-9.53), n = 72). Furthermore, digitally obtained ITGB4-high bud count in random TMA cores was better associated with survival outcome than visual tumour bud count in corresponding H&E-stained samples. In summary, the mIHC-based phenotypic profiling of human tumour tissue shows strong potential for the molecular characterisation of tumour biology and for the discovery of novel prognostic biomarkers.

Originalspråkengelska
TidskriftThe Journal of Pathology: Clinical Research
Volym5
Utgåva1
Sidor (från-till)63-78
Antal sidor16
ISSN2056-4538
DOI
StatusPublicerad - jan 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 3122 Cancersjukdomar
  • 3111 Biomedicinska vetenskaper
  • 114 Fysik

Citera det här

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title = "Combined epithelial marker analysis of tumour budding in stage II colorectal cancer",
abstract = "Tumour budding predicts survival of stage II colorectal cancer (CRC) and has been suggested to be associated with epithelial-to-mesenchymal transition (EMT). However, the underlying molecular changes of tumour budding remain poorly understood. Here, we performed multiplex immunohistochemistry (mIHC) to phenotypically profile tumours using known EMT-associated markers: E-cadherin (adherence junctions), integrin beta 4 (ITGB4; basement membrane), ZO-1 (tight junctions), and pan-cytokeratin. A subpopulation of patients showed high ITGB4 expression in tumour buds, and this coincided with a switch of ITGB4 localisation from the basal membrane of intact epithelium to the cytoplasm of budding cells. Digital image analysis demonstrated that tumour budding with high ITGB4 expression in tissue microarray (TMA) cores correlated with tumour budding assessed from haematoxylin and eosin (H&E) whole sections and independently predicted poor disease-specific survival in two independent stage II CRC cohorts (hazard ratio [HR] = 4.50 (95{\%} confidence interval [CI] = 1.50-13.5), n = 232; HR = 3.52 (95{\%} CI = 1.30-9.53), n = 72). Furthermore, digitally obtained ITGB4-high bud count in random TMA cores was better associated with survival outcome than visual tumour bud count in corresponding H&E-stained samples. In summary, the mIHC-based phenotypic profiling of human tumour tissue shows strong potential for the molecular characterisation of tumour biology and for the discovery of novel prognostic biomarkers.",
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author = "Khadija Slik and Sami Blom and Riku Turkki and Katja V{\"a}lim{\"a}ki and Samu Kurki and Harri Mustonen and Caj Haglund and Olli Carp{\'e}n and Olli Kallioniemi and Eija Korkeila and Jari Sundstr{\"o}m and Teijo Pellinen",
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Combined epithelial marker analysis of tumour budding in stage II colorectal cancer. / Slik, Khadija; Blom, Sami; Turkki, Riku; Välimäki, Katja; Kurki, Samu; Mustonen, Harri; Haglund, Caj; Carpén, Olli; Kallioniemi, Olli; Korkeila, Eija; Sundström, Jari; Pellinen, Teijo.

I: The Journal of Pathology: Clinical Research, Vol. 5, Nr. 1, 01.2019, s. 63-78.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - Combined epithelial marker analysis of tumour budding in stage II colorectal cancer

AU - Slik, Khadija

AU - Blom, Sami

AU - Turkki, Riku

AU - Välimäki, Katja

AU - Kurki, Samu

AU - Mustonen, Harri

AU - Haglund, Caj

AU - Carpén, Olli

AU - Kallioniemi, Olli

AU - Korkeila, Eija

AU - Sundström, Jari

AU - Pellinen, Teijo

N1 - doi: 10.1002/cjp2.119

PY - 2019/1

Y1 - 2019/1

N2 - Tumour budding predicts survival of stage II colorectal cancer (CRC) and has been suggested to be associated with epithelial-to-mesenchymal transition (EMT). However, the underlying molecular changes of tumour budding remain poorly understood. Here, we performed multiplex immunohistochemistry (mIHC) to phenotypically profile tumours using known EMT-associated markers: E-cadherin (adherence junctions), integrin beta 4 (ITGB4; basement membrane), ZO-1 (tight junctions), and pan-cytokeratin. A subpopulation of patients showed high ITGB4 expression in tumour buds, and this coincided with a switch of ITGB4 localisation from the basal membrane of intact epithelium to the cytoplasm of budding cells. Digital image analysis demonstrated that tumour budding with high ITGB4 expression in tissue microarray (TMA) cores correlated with tumour budding assessed from haematoxylin and eosin (H&E) whole sections and independently predicted poor disease-specific survival in two independent stage II CRC cohorts (hazard ratio [HR] = 4.50 (95% confidence interval [CI] = 1.50-13.5), n = 232; HR = 3.52 (95% CI = 1.30-9.53), n = 72). Furthermore, digitally obtained ITGB4-high bud count in random TMA cores was better associated with survival outcome than visual tumour bud count in corresponding H&E-stained samples. In summary, the mIHC-based phenotypic profiling of human tumour tissue shows strong potential for the molecular characterisation of tumour biology and for the discovery of novel prognostic biomarkers.

AB - Tumour budding predicts survival of stage II colorectal cancer (CRC) and has been suggested to be associated with epithelial-to-mesenchymal transition (EMT). However, the underlying molecular changes of tumour budding remain poorly understood. Here, we performed multiplex immunohistochemistry (mIHC) to phenotypically profile tumours using known EMT-associated markers: E-cadherin (adherence junctions), integrin beta 4 (ITGB4; basement membrane), ZO-1 (tight junctions), and pan-cytokeratin. A subpopulation of patients showed high ITGB4 expression in tumour buds, and this coincided with a switch of ITGB4 localisation from the basal membrane of intact epithelium to the cytoplasm of budding cells. Digital image analysis demonstrated that tumour budding with high ITGB4 expression in tissue microarray (TMA) cores correlated with tumour budding assessed from haematoxylin and eosin (H&E) whole sections and independently predicted poor disease-specific survival in two independent stage II CRC cohorts (hazard ratio [HR] = 4.50 (95% confidence interval [CI] = 1.50-13.5), n = 232; HR = 3.52 (95% CI = 1.30-9.53), n = 72). Furthermore, digitally obtained ITGB4-high bud count in random TMA cores was better associated with survival outcome than visual tumour bud count in corresponding H&E-stained samples. In summary, the mIHC-based phenotypic profiling of human tumour tissue shows strong potential for the molecular characterisation of tumour biology and for the discovery of novel prognostic biomarkers.

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KW - colorectal cancer

KW - multiplex immunohistochemistry

KW - digital pathology

KW - integrin β4

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KW - prognostics

KW - tumour budding

KW - colorectal cancer

KW - multiplex immunohistochemistry

KW - digital pathology

KW - integrin beta 4

KW - epithelial-to-mesenchymal transition

KW - prognostics

KW - MESENCHYMAL TRANSITION

KW - PROGNOSTIC MARKER

KW - EXPRESSION

KW - INTEGRIN

KW - PROTEIN

KW - RECOMMENDATIONS

KW - ALPHA-6-BETA-4

KW - CARCINOMAS

KW - 3122 Cancers

KW - 3111 Biomedicine

KW - 114 Physical sciences

U2 - 10.1002/cjp2.119

DO - 10.1002/cjp2.119

M3 - Article

VL - 5

SP - 63

EP - 78

JO - The Journal of Pathology: Clinical Research

JF - The Journal of Pathology: Clinical Research

SN - 2056-4538

IS - 1

ER -