Novo marcador biológico de sobrevida em doentes com cancro do estômago

Estudo alerta para a necessidade de se reformular a abordagem terapêutica tendo em conta as alterações no gene da Caderina-E.

O cancro do estômago é, a nível mundial, a segunda causa de morte por cancro. A ideia do estudo, que foi agora publicado e alvo de um Editorial no  Journal of Clinical Oncology (Jornal oficial da American Society of  Clinical Oncology), foi analisar sistematicamente a frequência e  
impacto de alterações somáticas no gene da Caderina-E no prognóstico e sobrevida de doentes com cancro gástrico. De particular interesse foi  
o facto de cerca de 30% de todos os cancros de estômago apresentarem alterações do gene da Caderina-E. As alterações que afectam a estrutura do gene (mutações pontuais ou delecções longas) estão associadas a menor sobrevida, principalmente se ocorrerem em doentes com história familiar de cancro gástrico de  tipo intestinal. Assim, e pela primeira vez, este trabalho propõe o uso da pesquisa de alterações da Caderina-E nos tumores gástricos, como biomarcador de estratificação terapêutica.

Autores:
Giovanni Corso*, Joana Carvalho*, Daniele Marrelli, Carla Vindigni, Beatriz Carvalho, Raquel Seruca, Franco Roviello, and Carla Oliveira. Somatic mutations and deletions of the E-cadherin gene predict poor survival of gastric cancer patients. J Clin Oncol. JCO published online on January 22, 2013; DOI:10.1200/JCO.2012.44.4612. Editorial do artigo disponivel em doi: 10.1200/JCO.2012.47.1714;
Podcast por Dr Ford no site www.jco.org/podcasts

*Autores com contribuição equivalente.

Afiliações:
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
Giovanni Corso, Joana Carvalho, Raquel Seruca, and Carla Oliveira
University of Porto, Portugal
Giovanni Corso, Joana Carvalho, Raquel Seruca, and Carla Oliveira
University of Siena and Instituto Toscano Tumori; Carla Vindigni, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Giovanni Corso, Daniele Marrelli, and Franco Roviello
VU University Medical Center, Amsterdam, the Netherlands
Beatriz Carvalho

Resumo:
Purpose: The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC.

Patients and Methods: A series of patients with sporadic and familial GC (diffuse and intestinal; n _ 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed.

Results: CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families.

Conclusion: CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease.

Link da publicação:
http://jco.ascopubs.org/content/early/recent