PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome

Fernanda Franco Munari,Antônio Talvane Torres De Oliveira,Denise Peixoto Guimarães,Eduardo Crema,Cristovam Scapulatempo-Neto,Adhemar Longatto-Filho,Rui Manuel Reis,Sheila Jorge Adad,Croider Franco Lacerda,Maria Aparecida Coelho Arruda Henry,Adriana Cruvinel-Carloni,Sandra Regina Morini Da Silva,Maria Aparecida Marchesan Rodrigues

doi:10.1186/s13027-018-0216-3

Abstract

BackgroundChronic diseases such as chagasic megaesophagus (secondary to Chagas’ disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood.ObjectiveWe analyzed hotspot PIK3CA gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of PIK3CA mutations with patients’ clinical and pathological features.MethodsThe study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). PIK3CA hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique.ResultsPIK3CA mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, PIK3CA mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between PIK3CA mutations and patients’ clinical features or TP53 mutation profile.ConclusionThis is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus. The detection of PIK3CA mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.

Highlights

Esophageal cancer is the eighth most frequent type of cancer in the world and the sixth most lethal, occurring mainly in developing countries such as Brazil [1]
This is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus
The detection of PIK3CA mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targetedtherapies for these diseases

Summary

Introduction

Esophageal cancer is the eighth most frequent type of cancer in the world and the sixth most lethal, occurring mainly in developing countries such as Brazil [1]. In Brazil, one of the endemic regions of Chagas’ disease, approximately 4 million people are infected with the parasite and about 6–7% of these patients will develop chagasic megaesophagus [5] Patients affected with this lesion are more likely to develop ESCC (3–10%) when compared to the general population [4]. Chronic diseases such as chagasic megaesophagus (secondary to Chagas’ disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; the molecular mechanisms involved are poorly understood

Methods

Results

Discussion

Conclusion