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

• Main Authors: Fernanda Franco Munari, Adriana Cruvinel-Carloni, Croider Franco Lacerda, Antônio Talvane Torres de Oliveira, Cristovam Scapulatempo-Neto, Sandra Regina Morini da Silva, Eduardo Crema, Sheila Jorge Adad, Maria Aparecida Marchesan Rodrigues, Maria Aparecida Coelho Arruda Henry, Denise Peixoto Guimarães, Adhemar Longatto-Filho, Rui Manuel Reis
• Format: Article
• Language: English
• Published: BMC 2018-12-01
• Series: Infectious Agents and Cancer
• Subjects: Esophageal cancer; Trypanosoma cruzi; Achalasia; Esophageal squamous cell carcinoma; Chagasic megaesophagus; PIK3CA
• Online Access: http://link.springer.com/article/10.1186/s13027-018-0216-3

Abstract Background Chronic 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. Objective We 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. Methods The 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. Results PIK3CA 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. Conclusion 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 targeted-therapies for these diseases.