Presence of Microsatellite Instability in Esophageal Squamous Cell Carcinoma Associated with Chagasic Megaesophagus

Campanella, Nathália C.; Lacerda, Croider Franco; Berardinelli, Gustavo Nóriz; Abrahão-Machado, Lucas Faria; Cruvinel-Carloni, Adriana; Oliveira, Antoonio Talvane Torres de; Scapulatempo‐Neto, Cristovam; Crema, Eduardo; Adad, Sheila Jorge; Rodrigues, Maria Aparecida Marchesan; Henry, Maria Aparecida Coelho Arruda; Guimarães, Denise Peixoto; Reis, Rui Manuel

doi:10.2217/bmm-2017-0329

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…The patients with esophageal squamous cell carcinoma without chagasic megaesophagus were all serologic negative for Chagas’ disease and had exams (imaging and histopathology) that confirmed malignant disease. These patients were previously described for their clinical-pathological and molecular TP53 and MSI features [7, 8].…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group showed the high frequency (13/32, 40.6%) of TP53 mutations in ESCC associated with chagasic megaesophagus [7]. Moreover, we also reported the presence of microsatellite instability (MSI) in a small fraction (1/19, 5.3%) of cases [8]. However, many other genes are known to be involved in ESCC carcinogenesis as demonstrated by the TCGA consortium [9].…”

Section: Introductionmentioning

confidence: 99%

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

Munari

Cruvinel-Carloni

Lacerda

et al. 2018

Infect Agents Cancer

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Munari

Cruvinel-Carloni

Lacerda

et al. 2018

Infect Agents Cancer

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“…We included only patients diagnosed with an image or histopathological proven chagasic megaesophagus with or without a positive serologic test for Chagas' disease; we also included patients with ESCC without chagasic megaesophagus serologic negative for Chagas' disease whose exams (image and histopathology) con rmed the malignant disease. Clinical-pathological variables of patients, as well as the molecular status of TP53 and PI3KCA hotspot mutations and MSI phenotype, were previously reported from these individuals 21,32,33 . All clinical and pathological information was obtained through medical record´s review.…”

Section: Inclusion Criteriamentioning

confidence: 98%

“…11, 70; 6 probably high risk: HPV-26, 53, 66, 68, 73, 82; and 11 high risk: HPV-16,18,31,33,35,39,45,52,56,58,59 …”

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confidence: 99%

Frequency of HPV detection in chagasic megaesophagus associated or not with esophageal squamous cell carcinoma

Munari

Sichero

Cruvinel-Carloni

et al. 2020

Preprint

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Abstract Background: Chagasic megaesophagus (clinical manifestation of chagasic disease) has been reported as an etiological factor for squamous cell carcinoma of the esophagus, as well as the presence of human papillomavirus (HPV). Objective: We accessed the prevalence of HPV DNA in a series of squamous cell carcinomas of the esophagus associated or not with the chagasic megaesophagus, and within samples of chagasic megaesophagus without cancer. Data obtained was further correlated to the pathological clinical data of affected individuals. Methods: Retrospective study that used a total 92 samples tissue/biopsy specimens of formalin fixed and paraffin embedded tissues were retrospectively collected from the southeast region of Brazil from patients treated in three hospitals: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro (UFTM), Uberaba, Minas Gerais; and São Paulo State University (UNESP), Botucatu, São Paulo. Cases were divided in three groups: i) 24 patients with chagasic megaesophagus associated with esophageal ESCC (CM/ESCC); ii) 37 patients with esophageal ESCC without chagasic megaesophagus (ESCC); iii) 31 patients with chagasic megaesophagus without esophageal ESCC (CM). Results: We detected a higher prevalence of high-risk HPVs in patients from both CM (12/31, 38.8%) and CM/ESCC groups (8/24, 33.3%), as compared to individuals of the ESCC group (6/37, 16.3%), although data was not statistically significant. We further observed that HPV-16 was more prevalent in patients of the ESCC (4/9, 44.5%) and CM/ESCC groups (2/8, 25.0%). In addition, some of these samples presented infection by multiple HPV types. High-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73, of which the majority was identified in patients from the CM group. Furthermore, low-risk HPV-11 and HPV70 were identified in individuals from both ESCC and CM groups. Conclusion: This is the first report regarding the presence of HPV DNA in megaesophagus associated with esophageal squamous cell carcinoma. In the present study, HPV infection appears to be directly related to the development of esophageal squamous cell carcinoma in patients with chagasic megaesophagus. Further studies are warrantee to confirm and better understand the role of oncogenic HPV persistent infection in these patients.

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“…Finally, Chagasic achalasia squamous cell carcinoma patients also present a higher rate of microsatellite instability than non-achalasia squamous cell carcinoma (21% vs. 11%) [34]. This finding may point to future immunotherapy options for these patients since microsatellite instability is a surrogate prognostic biomarker for immunotherapy in other cancer types [35].…”

Section: Esophageal Squamous Cell Carcinomamentioning

confidence: 99%

The Mechanisms for the Association of Cancer and Esophageal Dysmotility Disorders

et al. 2021

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Background: Achalasia and other esophageal dysmotility disorders mimicking achalasia can be associated with cancer. This study aimed to review the main mechanisms for which cancer may develop in esophageal dysmotility disorder patients. Methods: A narrative review was performed. Results: The mechanism for developing squamous cell carcinoma and adenocarcinoma are discussed. Besides, achalasia-like syndromes related to familial KIT-gene mutation and pseudoachalasia are discussed. Conclusions: Knowing the main mechanism for which achalasia can be related to cancer is essential for clinicians to conduct the proper investigation, surveillance, and treatment.

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Presence of Microsatellite Instability in Esophageal Squamous Cell Carcinoma Associated with Chagasic Megaesophagus

Abstract: Taking together, we concluded that MSI is a rare event in esophageal squamous cell carcinoma, but can be associated with CM.

Cited by 10 publications

References 31 publications

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

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

Frequency of HPV detection in chagasic megaesophagus associated or not with esophageal squamous cell carcinoma

The Mechanisms for the Association of Cancer and Esophageal Dysmotility Disorders

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