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

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.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.CAPES and FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo [Grant number 2015/20077–3 to FFM] and Barretos Cancer Hospital internal research funds (PAIP)info:eu-repo/semantics/publishedVersio

Blast phase myeloproliferative neoplasm: Mayo-AGIMM study of 410 patients from two separate cohorts

A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP) were retrospectively reviewed: 248 from theMayo Clinic and 162 from Italy. Median survival was 3.6 months, with no improvement over the last 15 years. Multivariableanalysis performed on the Mayo cohort identified high risk karyotype, platelet count 65 years andtransfusion need as independent risk factors for survival. Also in the Mayo cohort, intensive chemotherapy resulted in completeremission (CR) or CR with incomplete count recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5-yearsurvival rates were 32/10% for patients receiving allogeneic stem cell transplant (AlloSCT) (n = 24), 19/13% for patientsachieving CR/CRi but were not transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n = 200) (p <0.01). The survival impact of AlloSCT (HR 0.2, 95% CI 0.1--0.3), CR/CRi without AlloSCT (HR 0.3, 95% CI 0.2--0.5), high riskkaryotype (HR 1.6, 95% CI 1.1--2.2) and platelet count < 100 × 109/L (HR 1.6, 95% CI 1.1--2.2) were confirmed to be interindependent. Similar observations were made in the Italian cohort. The current study identifies the setting for improved short-termsurvival in MPN-BP, but also highlights the limited value of current therapy, including AlloSCT, in securing long-term survival