Abstract

BackgroundCellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant therapy.MethodsWe evaluated cell nest size and tumour budding activity in 122 post-neoadjuvant ESCC resections, correlated the results with tumour regression groups and patient survival and compared the results with data from primary resected cases as well as pre-therapeutic biopsies.ResultsCDG remained stable when results from pre-therapeutic biopsies and post-therapeutic resections from the same patient were compared. CDG was associated with therapy response and a strong predictor of overall, disease-specific (DSS) and disease-free (DFS) survival in univariate analysis and—besides metastasis—remained the only significant survival predictor for DSS and DFS in multivariate analysis. Multivariate DFS hazard ratios reached 3.3 for CDG-G2 and 4.9 for CDG-G3 neoplasms compared with CDG-G1 carcinomas (p = 0.016).ConclusionsCDG is the only morphology-based grading algorithm published to date, which in concert with regression grading, is able to contribute relevant prognostic information in the post-neoadjuvant setting of ESCC.

Highlights

  • Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC)

  • When we subdivided our cohort according to regression grade and stratified the subgroups for Cellular Dissociation Grade,[13,14] we found that the prognostic effect of Cellular Dissociation Grade on survival was visible in the group of tumours with subtotal regression

  • In this study, we investigated the transferability of Cellular Dissociation Grading based on tumour budding and cell nest size, which has already been established in primary resection specimens[26] as well as in pre-therapeutic biopsies of oesophageal squamous cell carcinoma,[25] to the neoadjuvant setting by evaluating these factors in a large cohort of 122 ESCC specimens resected following

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Summary

Introduction

Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). A novel grading approach termed Cellular Dissociation Grade (CDG) based on the evaluation of tumour budding and cell nest size, which are histologic factors that measure the extent of cellular dissociation either from a quantitative (tumour budding) or a qualitative (cell nest size) angle, was proposed for squamous cell carcinomas from various anatomic sites.[22,23,24] In ESCC, Cellular Dissociation Grading has been shown to be a stage-independent predictor of the disease course when measured in pre-therapeutic biopsies[25] as well as in primary resection specimens.[26] the feasibility and the prognostic significance of the application of the Cellular Dissociation Grade in ESCC after neoadjuvant treatment has not been investigated so far

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