Histopathological features have limited correlation with gene expression-based classifiers
Abstract
Abstract 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, (4) tumor budding and two gene expression-based classifiers, (1) consensus molecular subtypes (CMS), (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin-stained sections of the most invasive part of the primary tumor of 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 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 positively 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 strongly associated with CMS3: mucus was present in 64.1% of all CMS3 tumors. Although a strong 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 that histopathologic features have limited correlation with CMS and CRIS subtypes. Identification of distinct molecular subtypes using histopathology alone proved to be infeasible. Our findings also indicate that histopathologic features and molecular subtypes should be seen as distinct biomarkers. Combining both molecular and morphologic features could potentially improve patient stratification.
Authors 12
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Simone van de Weerd Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Leiden University Medical Center
Radboud University Medical Center
Sidra Medicine
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Marloes A. Smit Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Leiden University Medical Center
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Radboud University Medical Center
Sidra Medicine
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Jessica P Roelands Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Leiden University Medical Center
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Radboud University Medical Center
Sidra Medicine
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Wilma E. Mesker Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Sidra Medicine
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Leiden University Medical Center
Radboud University Medical Center
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Davide Bedognetti Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Sidra Medicine
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Leiden University Medical Center
Radboud University Medical Center
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Peter J.K. Kuppen Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Leiden University Medical Center
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Radboud University Medical Center
Sidra Medicine
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Hein Putter Aachen
Leiden University Medical Center
Affiliation as printed
LUMC
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Rob A.�E.�M. Tollenaar Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
LUMC
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Leiden University Medical Center
Radboud University Medical Center
Sidra Medicine
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University Medical Center Utrecht
Affiliation as printed
University Medical Center Utrecht
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Wouter Hendrickx Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Sidra Medicine
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Leiden University Medical Center
Radboud University Medical Center
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Jan Paul Medema Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Leiden University Medical Center
Radboud University Medical Center
Sidra Medicine
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J. Han van Krieken Aachen
Leiden University Medical Center · Radboud University Medical Center · University Medical Center Utrecht · Sidra Medical and Research Center · Amsterdam University Medical Centers
Affiliation as printed
Radboud University Medical Center
Amsterdam University Medical Center
LUMC Jeanine Roodhart University Medical Center Utrecht
Leiden University Medical Center
Sidra Medicine
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