Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients

<div><p>The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus mol...

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التفاصيل البيبلوغرافية
المؤلف الرئيسي: Simone van de Weerd (18282199) (author)
مؤلفون آخرون: Marloes A. Smit (18282202) (author), Jessica Roelands (7516439) (author), Wilma E. Mesker (2801620) (author), Davide Bedognetti (2632474) (author), Peter J. K. Kuppen (9858902) (author), Hein Putter (73805) (author), Rob A. E. M. Tollenaar (8115839) (author), Jeanine M. L. Roodhart (12205088) (author), Wouter Hendrickx (44559) (author), Jan Paul Medema (264579) (author), J. Han J. M. van Krieken (4477282) (author)
منشور في: 2022
الموضوعات:
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author Simone van de Weerd (18282199)
author2 Marloes A. Smit (18282202)
Jessica Roelands (7516439)
Wilma E. Mesker (2801620)
Davide Bedognetti (2632474)
Peter J. K. Kuppen (9858902)
Hein Putter (73805)
Rob A. E. M. Tollenaar (8115839)
Jeanine M. L. Roodhart (12205088)
Wouter Hendrickx (44559)
Jan Paul Medema (264579)
J. Han J. M. van Krieken (4477282)
author2_role author
author
author
author
author
author
author
author
author
author
author
author_facet Simone van de Weerd (18282199)
Marloes A. Smit (18282202)
Jessica Roelands (7516439)
Wilma E. Mesker (2801620)
Davide Bedognetti (2632474)
Peter J. K. Kuppen (9858902)
Hein Putter (73805)
Rob A. E. M. Tollenaar (8115839)
Jeanine M. L. Roodhart (12205088)
Wouter Hendrickx (44559)
Jan Paul Medema (264579)
J. Han J. M. van Krieken (4477282)
author_role author
dc.creator.none.fl_str_mv Simone van de Weerd (18282199)
Marloes A. Smit (18282202)
Jessica Roelands (7516439)
Wilma E. Mesker (2801620)
Davide Bedognetti (2632474)
Peter J. K. Kuppen (9858902)
Hein Putter (73805)
Rob A. E. M. Tollenaar (8115839)
Jeanine M. L. Roodhart (12205088)
Wouter Hendrickx (44559)
Jan Paul Medema (264579)
J. Han J. M. van Krieken (4477282)
dc.date.none.fl_str_mv 2022-10-21T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/ijms232012707
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Correlation_of_Immunological_and_Histopathological_Features_with_Gene_Expression-Based_Classifiers_in_Colon_Cancer_Patients/25516543
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Chemical sciences
Inorganic chemistry
Organic chemistry
Theoretical and computational chemistry
colon cancer
histopathology
consensus molecular subtypes
CRC intrinsic subtypes
tumor infiltrating lymphocytes
mucinous adenocarcinoma
tumor-stroma ratio
tumor budding
dc.title.none.fl_str_mv Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms232012707" target="_blank">https://dx.doi.org/10.3390/ijms232012707</a></p>
eu_rights_str_mv openAccess
id Manara2_93a70714f7132e7d93cc00ca6631cc45
identifier_str_mv 10.3390/ijms232012707
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25516543
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spelling Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer PatientsSimone van de Weerd (18282199)Marloes A. Smit (18282202)Jessica Roelands (7516439)Wilma E. Mesker (2801620)Davide Bedognetti (2632474)Peter J. K. Kuppen (9858902)Hein Putter (73805)Rob A. E. M. Tollenaar (8115839)Jeanine M. L. Roodhart (12205088)Wouter Hendrickx (44559)Jan Paul Medema (264579)J. Han J. M. van Krieken (4477282)Chemical sciencesInorganic chemistryOrganic chemistryTheoretical and computational chemistrycolon cancerhistopathologyconsensus molecular subtypesCRC intrinsic subtypestumor infiltrating lymphocytesmucinous adenocarcinomatumor-stroma ratiotumor budding<div><p>The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.</p><p> </p></div><h2>Other Information</h2> <p> Published in: International Journal of Molecular Sciences<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms232012707" target="_blank">https://dx.doi.org/10.3390/ijms232012707</a></p>2022-10-21T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms232012707https://figshare.com/articles/journal_contribution/Correlation_of_Immunological_and_Histopathological_Features_with_Gene_Expression-Based_Classifiers_in_Colon_Cancer_Patients/25516543CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/255165432022-10-21T03:00:00Z
spellingShingle Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
Simone van de Weerd (18282199)
Chemical sciences
Inorganic chemistry
Organic chemistry
Theoretical and computational chemistry
colon cancer
histopathology
consensus molecular subtypes
CRC intrinsic subtypes
tumor infiltrating lymphocytes
mucinous adenocarcinoma
tumor-stroma ratio
tumor budding
status_str publishedVersion
title Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
title_full Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
title_fullStr Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
title_full_unstemmed Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
title_short Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
title_sort Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
topic Chemical sciences
Inorganic chemistry
Organic chemistry
Theoretical and computational chemistry
colon cancer
histopathology
consensus molecular subtypes
CRC intrinsic subtypes
tumor infiltrating lymphocytes
mucinous adenocarcinoma
tumor-stroma ratio
tumor budding