122P - Distinct transcriptomic immune profiling and clinicopathological features of cribriform morphology in colorectal adenocarcinomas

Background

Cribriform (cbf) morphology has been shown in carcinomas from various organs, including prostate and breast, to be associated with worse patient outcomes and unique molecular features. We sought to examine the multimodal data from the landmark Cancer Genome Atlas (TCGA) study to clarify molecular and prognostic factors associated with cbf morphology in colorectal adenocarcinomas.

Methods

We retrospectively analyzed the available TCGA CRC cohort (n=594). Clinicopathological, digital slides, and molecular data were extracted. Cases with insufficient clinical data, no diagnostic slides, or poor slide quality were excluded. TCGA coded data, pathology reports, and digital diagnostic slides were reassessed by one gastrointestinal pathologist and a resident. Cbf morphology was graded using five categories based on prostate cribriform studies: (0) no-cribriform, (1) loose cribriform, (2) small cribriforming glands, (3) diffuse large cribriform, and (4) intraductal carcinoma of the prostate-like. Cases were grouped into cbf 'low' (0-1) and cbf 'high' (2-4) groups, which were correlated with clinicopathological, histological and molecular features. Immune infiltration was characterized by cell type fraction. An adjusted α = 0.05 for statistical significance was used for all tests.

Results

573 CRC cases were included. Cbf 'high' CRCs (159/573) were associated with more left-sided tumors (p=0.049), metastatic diseases (p=0.0001), less MSI-H (p=0.003), and different aneuploidy and fraction genome altered (p=0.003-0.008). Cbf 'high' vs 'low' tumors did not show a significant difference in grading distribution. T and N staging were not associated with cbf morphology. By cell fraction, cbf ‘high’ CRCs showed an immune infiltrate with increased regulatory T cells (p<0.0001) but decreased memory B cells (p=0.046), M2 macrophages (p<0.0001), neutrophils (p=0.018), resting dendritic cells (p=0.046), compared with cbf ‘low’ CRCs. Cbf 'high' tumor morphology was associated with worse overall survival outcomes by log-rank testing (p=0.037).

Conclusions

Cribriform morphology in colorectal adenocarcinoma TCGA cases was associated with poorer outcomes and distinct transcriptomic immune profiling.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Q-H. Trinh.

Funding

Fonds de recherche Santé Québec.

Disclosure

All authors have declared no conflicts of interest.