Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type

Ana Flávia Costa,José Luis Llorente,Mario Hermsen,Carlos Suárez,Florentino Fresno,Albina Altemani,Hedy Vékony,Elisabeth Bloemena

doi:10.1155/2010/706205

Abstract

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC.Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed.Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

Highlights

Adenoid cystic carcinoma is a slow-growing tumor presenting a dual cellular composition, i.e., ductal and myoepithelial cell differentiation and three major growth patterns: tubular, cribriform and solid [6]
Five cases of adenoid cystic carcinomas (ACC)-HGT were obtained from the archives of the Department of Pathology of the University of Campinas, Brazil, 1 case of ACC-HGT of the Department of Pathology of the Hospital Universitario Central de Asturias, Spain and 5 cases of solid ACC of the Department of Pathology, VU University Medical Center, The Netherlands
The transformed component was identified according to the criteria described by Seethala et al [26] and all cases showed the following features: proliferation of tumor cells with at least a focal loss of myoepithelial cells surrounding tumor nests, nuclear size at least 2–3 times the size of tubular/cribriform ACC nuclei, thickened irregular nuclear membranes and prominent nucleoli in a majority of cells

Summary

Introduction

Adenoid cystic carcinoma is a slow-growing tumor presenting a dual cellular composition, i.e., ductal (luminal) and myoepithelial cell differentiation and three major growth patterns: tubular, cribriform and solid [6]. ACC can occasionally undergo transformation into poorly differentiated adenocarcinoma or undifferentiated carcinoma. This phenomenon has been referred to as dedifferentiation or high-grade transformation (ACC-HGT) and there have been only 33 reported cases so far [1,3,4,10,12,15,16,17,25,26]. This process was first believed to occur in low-grade ACCs without morphological recognizable changes, as an abrupt transition, but recently cases have been described.

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