Squamous cell carcinoma antigen (SCCA) is up-regulated during Barrett's carcinogenesis and predicts esophageal adenocarcinoma resistance to neoadjuvant chemotherapy.

Matteo Fassan,Luca Vianello,Santina Quarta,Vincenza Guzzardo,Vanna Chiarion Sileni,Massimo Rugge,Carlo Castoro,Giovanni Zaninotto,Alberto Ruol,Stefano Realdon,Marco Scarpa,Patrizia Pontisso

doi:10.18632/oncotarget.14108

Abstract

Squamous Cell Carcinoma Antigen (SCCA) is consistently overexpressed in many different solid tumors, and has been associated with both tumor aggressiveness and chemoresistance. No data, however, is currently available on SCCA expression during esophageal Barrett's carcinogenesis, nor on SCCA expression's role on esophageal adenocarcinoma chemoresistance. The SCCA immunohistochemical expression was assessed in a series of 100 biopsy samples covering the whole histological spectrum of Barrett's oncogenesis. Squamous native mucosa was characterized by a moderate to strong cytoplasmic and nuclear SCCA expression in suprabasal, medium, and superficial layers. On the other hand, almost half of the considered lesions did not express SCCA; the other half featured weak to moderate SCCA expression. The relationship between SCCA protein expression and tumor response to neoadjuvant chemotherapy was assessed in 90 esophageal adenocarcinoma specimens (40 biopsy and 50 surgery specimens), stratified according to Mandard tumor regression grade. As observed in other settings, the presence of SCCA expression clustered in the group of tumors characterized by a lower responsiveness to neoadjuvant treatments. The present results suggest an involvement of SCCA in a subset of Barrett-related tumors, and prompt to consider the SCCA-protein expression as response-predictive marker of neoadjuvant therapy in esophageal adenocarcinomas.

Highlights

Barrett’s esophagus is a complication of longstanding gastro-esophageal reflux and is a major risk for esophageal adenocarcinoma, one of the leading causes of cancer-related death worldwide [1,2,3,4].The recent advances in the therapeutic approaches for gastroesophageal tumors has significantly improved www.impactjournals.com/oncotarget the curative resection rates, and both the disease-free and the overall survival [5,6,7]
The present results suggest an involvement of Squamous Cell Carcinoma Antigen (SCCA) in a subset of Barrett-related tumors, and prompt to consider the SCCA-protein expression as response-predictive marker of neoadjuvant therapy in esophageal adenocarcinomas
We focused on the relationship between SCCA expression and tumor response to neoadjuvant chemotherapy, as assessed by Mandard scale Tumor Regression Grade (TRG) [17]

Summary

Introduction

The recent advances in the therapeutic approaches for gastroesophageal tumors has significantly improved www.impactjournals.com/oncotarget the curative resection rates, and both the disease-free and the overall survival [5,6,7]. Squamous cell carcinoma antigen (SCCA), including its two isoforms SCCA-1 ( known as SerpinB3) and SCCA-2 ( known as SerpinB4), belongs to the clade B subset of serpins [8,9,10]. The first described isoform, SCCA-1, was initially found to be significantly overexpressed in carcinomas with squamous differentiation and in hepatocellular carcinoma [11,12,13]. Other studies pinpointed a significant association between SCCA-1 overexpression, more aggressive tumor phenotypes and chemoresistance in different tumor types [8, 14,15,16]

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Results

Conclusion