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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Munari, Fernanda Franco [1] ; Cruvinel-Carloni, Adriana [1] ; Lacerda, Croider Franco [1, 2] ; Torres de Oliveira, Antonio Talvane [2] ; Scapulatempo-Neto, Cristovam [3] ; Morini da Silva, Sandra Regina [3] ; Crema, Eduardo [4] ; Adad, Sheila Jorge [4] ; Marchesan Rodrigues, Maria Aparecida [5] ; Coelho Arruda Henry, Maria Aparecida [5] ; Guimaraes, Denise Peixoto [6, 1] ; Longatto-Filho, Adhemar [7, 1, 8, 9] ; Reis, Rui Manuel [7, 10, 1]
Total Authors: 13
Affiliation:
[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil
[2] Barretos Canc Hosp, Dept Digest Surg, Barretos, SP - Brazil
[3] Barretos Canc Hosp, Dept Pathol Diag Biopsies & Surg Specimens, Barretos, SP - Brazil
[4] UFTM Fed Univ Triangulo Mineiro, Med Sch, Dept Digest Surg & Pathol, Uberaba, MG - Brazil
[5] Sao Paulo State Univ, UNESP, Med Sch, Dept Gastroenterol Surg & Pathol, Botucatu, SP - Brazil
[6] Barretos Canc Hosp, Dept Endoscopy, Barretos, SP - Brazil
[7] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga - Portugal
[8] Univ Sao Paulo, Med Sch, Dept Radiol & Oncol, Sao Paulo - Brazil
[9] Univ Sao Paulo, Med Sch, Dept Pathol, Med Lab Med Invest LIM 14, Sao Paulo - Brazil
[10] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal
Total Affiliations: 10
Document type: Journal article
Source: INFECTIOUS AGENTS AND CANCER; v. 13, DEC 29 2018.
Web of Science Citations: 1
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 5months), when compared to wild-type patients (mean 2.0years). 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. (AU)

FAPESP's process: 15/20077-3 - High-risk HPV DNA detection and analysis of the mutational status of KRAS and PIK3CA genes and inflammatory cytokines panel in patients with esophageal cancer and megaesophagus with and without cancer
Grantee:Fernanda Franco Munari
Support Opportunities: Scholarships in Brazil - Master