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DNA repair defect and RAS mutation in Schistosoma mansoni-associated colorectal cancer patients: Carcinogenesis steps or mere coincidence?
Abstract   Peer reviewed

DNA repair defect and RAS mutation in Schistosoma mansoni-associated colorectal cancer patients: Carcinogenesis steps or mere coincidence?

Gustavo Fernandes Godoy Almeida, Luiz Alberto Reis Mattos, Joao Bosco Oliveira Filho, Paula Carvalho, Bruno Rolim de Brito, Estela Reis Alcantara, Caroline Teixeira Pinto, Filipe W Sarinho, Andre M Galvao, Mauricio Assuero Lima de Freitas, …
Journal of clinical oncology, Vol.34(15_suppl), pp.e23279-e23279
05/20/2016
DOI: 10.1200/JCO.2016.34.15_suppl.e23279

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Abstract

Background: Data on Schistosoma mansoni-associated colon cancer is scarce. Infestion induces inflammation which may trigger genetic mutations. We report two pts and potentially implicated carcinogenesis. Methods: KRAS/NRAS exons 2, 3 and 4 were amplified by PCR and second-generation sequencing by Illumina MiSeq. Pts were tested for MSI using immunohistochemistry antibodies MLH1, MSH2, MSH6, and PMS2. Results: 1) 45 year-old female, abdominal pain, weight loss and diarrhea. Colonoscopy Oct 2014, 3 cm tumor in cecum. Right colectomy in Jan 2015. Well differentiated mucinous adenocarcinoma. 2.5 x 1.5 x 1.5 cm invasion into muscularis propria. No perineural or lymphovascular invasion. Mild tumor inflammatory infiltrate. Free margins, metastasis to 1 of 24 lymph nodes. Ileal schistosomiasis found. MSI confirmed (loss of MLH1 and PMS2). All-RAS mutation negative. Six-month adj CAPOX. Last visit Dec 2015. 2) 47 year-old male, hepatosplenic form. Right hemicolectomy in 2012 due to complications of appendicitis. Mar 2014, splenectomy and esophageal varices clamp due to GI hemorrhage. He presented diarrhea and in Nov 2014, colonoscopy showed 2 cm tumor next to ileum-transverse colon anastomosis. Mar 2015, segmental colectomy. Ileum: granulomatous reaction in response to Schistosoma eggs; Merkel diverticula; 3.5 x 1.8 cm mucinous moderately differentiated adenocarcinoma infiltrating subserosa, free margins, lymphovascular invasion present, perineural infiltration absent. Mild tumor lymphocytic infiltrate. No lymph nodes were identified in the specimen. Other findings: diffuse granulomatous reaction in response to Schistosoma eggs in ileum and colonic mucosa. MSI negative. Exon 2 KRAS mutation (c.38G > A:p.G13D) was identified. No adj chemo. Last visit Dec 2015. Conclusions: age of patients and mucinous subtype were in accordance with literature. RAS mutation, along with the presence of MSI, may be implicated in the carcinogenesis of Schistosoma mansoni-associated colorectal cancer or represent coincidental events. If the first is right, it would determine screeeing, treatment and prognosis implications among Schistosoma mansoni infested patients.

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