Does heterogeneity matter in the estimation of tumour budding and tumour stroma ratio in colon cancer?

Ann C. Eriksen*, Johnnie B. Andersen, Jan Lindebjerg, René dePont Christensen, Torben F. Hansen, Sanne Kjær-Frifeldt, Flemming B. Sørensen

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Resumé

BACKGROUND: Tumour budding (TB) and Tumour Stroma Ratio (TSR) may be rewarding in the treatment stratification of patients with stage II colon cancer. However, lack of standardization may exclude these parameters from being used in a clinical setting. The purpose of this methodologic study was to compare stereology with semi-quantitative estimations of TSR, to investigate the intra-tumoural heterogeneity of TB and TSR, and to assess the intra- and inter-observer agreement.

METHODS: Three paraffin embedded tumour blocks, one of them representing the deepest invasive front, were selected from each of 43 patients treated for stage II colon cancer. TSR was estimated in H&E sections semi-quantitatively using conventional microscopy, and stereologically on scanned slides, using the newCAST stereology platform. TB was scored across 10 high power fields at the invasive front in cytokeratin AE1/AE3 stained sections.

RESULTS: Subjective, semi-quantitative estimates of TSR significantly correlated to the stereological estimates, with the best correlation found for sections with the deepest invasive tumour penetration (σ = 0.621, p < 0.001). Inter-observer agreement was moderate to substantial for both TB (Κappa = 0.46-0.73) and TSR (Κappa = 0.70-0.75). The Intraclass correlation coefficient (ICC) for TSR varied from 0.322 based on stereological hotspot estimation to 0.648 for the semi-quantitative evaluation. For TB, ICC varied from 0.646 based on continuous data to 0.698 based on categorical data (cut-off: 10 buds). Thus, the intra-tumoural heterogeneity for both TB and the semi-quantitative estimation of TSR was low.

CONCLUSION: We recommend using only one tissue section representing the deepest invasive tumour area for estimation of TSR. For TB we recommend using one tissue section; however due to low representation of high-budding tumours, results must be considered with caution.

OriginalsprogEngelsk
Artikelnummer20
TidsskriftDiagnostic Pathology
Vol/bind13
Antal sider9
ISSN1746-1596
DOI
StatusUdgivet - 20. mar. 2018

Fingeraftryk

Colonic Neoplasms
Neoplasms
Paraffin

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@article{f6318572b9cc4a82bd67ba6a353f2a73,
title = "Does heterogeneity matter in the estimation of tumour budding and tumour stroma ratio in colon cancer?",
abstract = "BACKGROUND: Tumour budding (TB) and Tumour Stroma Ratio (TSR) may be rewarding in the treatment stratification of patients with stage II colon cancer. However, lack of standardization may exclude these parameters from being used in a clinical setting. The purpose of this methodologic study was to compare stereology with semi-quantitative estimations of TSR, to investigate the intra-tumoural heterogeneity of TB and TSR, and to assess the intra- and inter-observer agreement.METHODS: Three paraffin embedded tumour blocks, one of them representing the deepest invasive front, were selected from each of 43 patients treated for stage II colon cancer. TSR was estimated in H&E sections semi-quantitatively using conventional microscopy, and stereologically on scanned slides, using the newCAST stereology platform. TB was scored across 10 high power fields at the invasive front in cytokeratin AE1/AE3 stained sections.RESULTS: Subjective, semi-quantitative estimates of TSR significantly correlated to the stereological estimates, with the best correlation found for sections with the deepest invasive tumour penetration (σ = 0.621, p < 0.001). Inter-observer agreement was moderate to substantial for both TB (Κappa = 0.46-0.73) and TSR (Κappa = 0.70-0.75). The Intraclass correlation coefficient (ICC) for TSR varied from 0.322 based on stereological hotspot estimation to 0.648 for the semi-quantitative evaluation. For TB, ICC varied from 0.646 based on continuous data to 0.698 based on categorical data (cut-off: 10 buds). Thus, the intra-tumoural heterogeneity for both TB and the semi-quantitative estimation of TSR was low.CONCLUSION: We recommend using only one tissue section representing the deepest invasive tumour area for estimation of TSR. For TB we recommend using one tissue section; however due to low representation of high-budding tumours, results must be considered with caution.",
keywords = "Colon cancer, Heterogeneity, Tumour budding, Tumour stroma ratio, Colonic Neoplasms/diagnosis, Prognosis, Soft Tissue Neoplasms/diagnosis, Humans, Middle Aged, Male, Colorectal Neoplasms/diagnosis, Immunohistochemistry/methods, Adenocarcinoma/diagnosis, Adult, Female, Aged",
author = "Eriksen, {Ann C.} and Andersen, {Johnnie B.} and Jan Lindebjerg and {dePont Christensen}, Ren{\'e} and Hansen, {Torben F.} and Sanne Kj{\ae}r-Frifeldt and S{\o}rensen, {Flemming B.}",
year = "2018",
month = "3",
day = "20",
doi = "10.1186/s13000-018-0697-9",
language = "English",
volume = "13",
journal = "Diagnostic Pathology",
issn = "1746-1596",
publisher = "BioMed Central",

}

Does heterogeneity matter in the estimation of tumour budding and tumour stroma ratio in colon cancer? / Eriksen, Ann C.; Andersen, Johnnie B.; Lindebjerg, Jan; dePont Christensen, René; Hansen, Torben F.; Kjær-Frifeldt, Sanne; Sørensen, Flemming B.

I: Diagnostic Pathology, Bind 13, 20, 20.03.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Does heterogeneity matter in the estimation of tumour budding and tumour stroma ratio in colon cancer?

AU - Eriksen, Ann C.

AU - Andersen, Johnnie B.

AU - Lindebjerg, Jan

AU - dePont Christensen, René

AU - Hansen, Torben F.

AU - Kjær-Frifeldt, Sanne

AU - Sørensen, Flemming B.

PY - 2018/3/20

Y1 - 2018/3/20

N2 - BACKGROUND: Tumour budding (TB) and Tumour Stroma Ratio (TSR) may be rewarding in the treatment stratification of patients with stage II colon cancer. However, lack of standardization may exclude these parameters from being used in a clinical setting. The purpose of this methodologic study was to compare stereology with semi-quantitative estimations of TSR, to investigate the intra-tumoural heterogeneity of TB and TSR, and to assess the intra- and inter-observer agreement.METHODS: Three paraffin embedded tumour blocks, one of them representing the deepest invasive front, were selected from each of 43 patients treated for stage II colon cancer. TSR was estimated in H&E sections semi-quantitatively using conventional microscopy, and stereologically on scanned slides, using the newCAST stereology platform. TB was scored across 10 high power fields at the invasive front in cytokeratin AE1/AE3 stained sections.RESULTS: Subjective, semi-quantitative estimates of TSR significantly correlated to the stereological estimates, with the best correlation found for sections with the deepest invasive tumour penetration (σ = 0.621, p < 0.001). Inter-observer agreement was moderate to substantial for both TB (Κappa = 0.46-0.73) and TSR (Κappa = 0.70-0.75). The Intraclass correlation coefficient (ICC) for TSR varied from 0.322 based on stereological hotspot estimation to 0.648 for the semi-quantitative evaluation. For TB, ICC varied from 0.646 based on continuous data to 0.698 based on categorical data (cut-off: 10 buds). Thus, the intra-tumoural heterogeneity for both TB and the semi-quantitative estimation of TSR was low.CONCLUSION: We recommend using only one tissue section representing the deepest invasive tumour area for estimation of TSR. For TB we recommend using one tissue section; however due to low representation of high-budding tumours, results must be considered with caution.

AB - BACKGROUND: Tumour budding (TB) and Tumour Stroma Ratio (TSR) may be rewarding in the treatment stratification of patients with stage II colon cancer. However, lack of standardization may exclude these parameters from being used in a clinical setting. The purpose of this methodologic study was to compare stereology with semi-quantitative estimations of TSR, to investigate the intra-tumoural heterogeneity of TB and TSR, and to assess the intra- and inter-observer agreement.METHODS: Three paraffin embedded tumour blocks, one of them representing the deepest invasive front, were selected from each of 43 patients treated for stage II colon cancer. TSR was estimated in H&E sections semi-quantitatively using conventional microscopy, and stereologically on scanned slides, using the newCAST stereology platform. TB was scored across 10 high power fields at the invasive front in cytokeratin AE1/AE3 stained sections.RESULTS: Subjective, semi-quantitative estimates of TSR significantly correlated to the stereological estimates, with the best correlation found for sections with the deepest invasive tumour penetration (σ = 0.621, p < 0.001). Inter-observer agreement was moderate to substantial for both TB (Κappa = 0.46-0.73) and TSR (Κappa = 0.70-0.75). The Intraclass correlation coefficient (ICC) for TSR varied from 0.322 based on stereological hotspot estimation to 0.648 for the semi-quantitative evaluation. For TB, ICC varied from 0.646 based on continuous data to 0.698 based on categorical data (cut-off: 10 buds). Thus, the intra-tumoural heterogeneity for both TB and the semi-quantitative estimation of TSR was low.CONCLUSION: We recommend using only one tissue section representing the deepest invasive tumour area for estimation of TSR. For TB we recommend using one tissue section; however due to low representation of high-budding tumours, results must be considered with caution.

KW - Colon cancer

KW - Heterogeneity

KW - Tumour budding

KW - Tumour stroma ratio

KW - Colonic Neoplasms/diagnosis

KW - Prognosis

KW - Soft Tissue Neoplasms/diagnosis

KW - Humans

KW - Middle Aged

KW - Male

KW - Colorectal Neoplasms/diagnosis

KW - Immunohistochemistry/methods

KW - Adenocarcinoma/diagnosis

KW - Adult

KW - Female

KW - Aged

U2 - 10.1186/s13000-018-0697-9

DO - 10.1186/s13000-018-0697-9

M3 - Journal article

VL - 13

JO - Diagnostic Pathology

JF - Diagnostic Pathology

SN - 1746-1596

M1 - 20

ER -