Novel Criteria for Intratumoral Budding with Prognostic Relevance for Colon Cancer and Its Histological Subtypes.

Pantea Pour Farid,Arndt Hartmann,Markus Eckstein,Michaela Benz,Robert Grützmann,Susanne Merkel,Volker Bruns,Regine Schneider-Stock,Carol I Geppert

doi:10.3390/ijms222313108

Abstract

Peritumoral budding and intratumoral budding (ITB) are important prognostic factors for colorectal cancer patients. Scientists worldwide have investigated the role of budding in tumor progression and its prognosis, but guidelines for reliably identifying tumor buds based on morphology are lacking. In this study, next-generation tissue microarray (ngTMA®) construction was used for tumor bud evaluation, and highly detailed rule-out annotation was used for tumor definition in pancytokeratin-stained tissue sections. Initially, tissues of 245 colon cancer patients were evaluated with high interobserver reliability, and a concordance of 96% was achieved. It was shown that high ITB scores were associated with poor distant metastasis-free survival (p = 0.006 with a cut-off of ≥10 buds). This cut-off was defined as the best maximum value from one of two/three ngTMA® cores (0.6 mm diameter). ITB in 30 cases of mucinous, medullary, and signet ring cell carcinoma was analyzed for the subsequent determination of differences in tumor bud analyses between those subtypes. In conclusion, blinded randomized punched cores in the tumor center can be useful for ITB detection. It can be assumed that this method is suitable for its adoption in clinical routines.

Highlights

Colorectal cancer (CRC) is one of the most aggressive cancers worldwide in terms of its incidence and mortality
Peritumoral and intratumoral budding in colorectal cancer was retrospectively analyzed in ngTMA® punches of 245 NOS adenocarcinoma patients
We evaluated intratumoral budding (ITB) according to the three histological subtypes: signet ring cell, medullary, and mucinous adenocarcinoma

Summary

Introduction

Colorectal cancer (CRC) is one of the most aggressive cancers worldwide in terms of its incidence and mortality. Tumor budding seems to be a relevant independent factor for the prognosis of patients with colorectal cancer (CRC). It is based on morphology and seems to outperform evaluations based on the WHO grade [4,5]. The availability of novel diagnostic markers that allow for the prediction of prognosis and the risk of metastasis could help clinicians in tailoring therapeutic strategies. We believe that novel and more detailed criteria for tumor budding should be integrated into routine diagnostics

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