Phenotypic Subtyping of Matched Primary Colonic Tumours and Liver Metastases


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Kathryn Pennel1,Arfon Powell2,Donald McMillan1,Paul Horgan1,Antonia Roseweir1,Joanne Edwards1
1University of Glasgow,2Cardif University

Abstract

Background

Colorectal cancer (CRC) is a heterogeneous group of malignancies that arise in the same organ. The 5-year survival rate for CRC is 60% and this is significantly reduced in stage four metastatic disease. A common site of metastasis is the liver. In 2017, phenotypic subtypes for CRC were developed in an effort to move towards precision medicine. The phenotypic subtypes (immune, canonical, latent and stromal) are derived from three features; inflammation, stromal invasion and proliferation. This study aimed to investigate the relationship between primary tumour and liver metastases phenotypic subtypes and association with clinicopathological outcomes.

Method

Matched patient-derived colonic primary tumours and liver metastases were stained for Ki67 proliferation index and an H&E analysed for Klintrup-Makinen grade and tumour-stroma-percentage to determine phenotypic subtype. The relationship between the primary tumour subtype (PS-primary) and liver metastases (PS-met) was investigated using bivariate correlations and paired sample T-tests. The relationship between PS-primary/PS-met and clinicopathological features was analysed using Chi-squared tests.

Results

Phenotypic subtype was observed to correlate between the primary tumour and metastasis (n=42, p=0.001). In the primary tumours, immune subtype associated with age (p=0.047) and nuclear HIF1a (p=0.043); canonical subtype associated with cytoplasmic MMP9 expression (p=0.015); latent subtype associated with marginal involvement (p=0.013); and stromal subtype associated with modified Glasgow Prognostic Score (p=0.044) and cytoplasmic HIF1a expression (p=0.012). In the metastases, immune subtype associated with age (p=0.01) and albumin levels (p=0.043); latent subtype associated with cytoplasmic MMP9 expression (p=0.031); and stromal subtype associated with cytoplasmic CRP expression (p=0.032). However, the canonical subtype showed no significant association.

Conclusion

The results suggest that PS-primary is predictive of PS-met, and that each phenotypic subtype associates with different specific clinicopathological features differing between primary or metastatic lesions. This may provide a step towards the development of precision medicine for CRC.