Importância e caracterização do carcinoma gástrico em famílias com diagnóstico ou suspeita de síndroma de lynch

 

I. Rosa ^1,2, I. Claro ^1,3, P. Lage ^1,3, S. Ferreira ^1,3, I. Francisco ⁴, P. Rodrigues ⁴, A. Suspiro ^1,5, P. Chaves ⁵, C. Albuquerque ⁴, C. Nobre-Leitão ^1,4

 

 

Resumo

Introdução: A Síndroma de Lynch (SL) confere um risco elevado para carcinoma do cólon e recto, mas também para outros tumores. Não é consensual se o carcinoma gástrico (CG) deve ser incluído no seu espectro, sobretudo em países com incidência elevada para esta neoplasia.

Objectivos: Em famílias com diagnóstico ou suspeita de SL e na presença de CG, caracterizar estes tumores e comparálos com um grupo de CG esporádicos.

Métodos: Foram incluídos 25 doentes pertencentes a 20 famílias com diagnóstico ou suspeita de SL, nos quais se obteve confirmação histológica do CG. As famílias cumpriam: Critérios de Amesterdão (n=12); Critérios de Bethesda (n=2) ou Critérios de Amesterdão apenas se considerado o CG (SL atípica; n=6). No grupo dos esporádicos, incluíram-se 58 doentes consecutivos com CG. Analisaram-se: sexo, idade de diagnóstico, localização, tipo histológico, grau de diferenciação, estádio e tratamento cirúrgico do CG. No grupo com SL, efectuou-se análise mutacional para os genes MLH1 e MSH2 por DGGE/MLPA e sequenciação directa.

Resultados: Os doentes com CG em SL eram mais jovens, tendo os CG sido mais frequentemente detectados em fase precoce e submetidos a cirurgia de intenção curativa (p=0,045). O carcinoma mucocelular foi mais frequente nos CG esporádicos e o mucinoso nos associados à SL (p=0,014). O diagnóstico genético foi inconclusivo em todas as famílias com SL atípica testadas e positivo em 73% das famílias com SL clássica (p=0,02). Registaram-se mais frequentemente outros tumores do espectro nos doentes com CG pertencentes a famílias com mutação identificada (p=0,002) e nenhum ocorreu nos casos de SL atípica (p=0,009).

Conclusões: Um subgrupo de doentes com CG pertencentes a famílias com SL apresentou características que favorecem, de forma significativa, a inclusão desta neoplasia no seu espectro tumoral. Nas famílias com SL atípica, a presença de CG não parece contribuir para a confirmação do diagnóstico desta entidade. Seria útil identificar marcadores que indicassem quais os CG que com maior probabilidade pertencerão ao espectro tumoral da SL.

 

 

Summary

Background: Lynch Syndrome (LS) is associated with an increased risk of colorectal cancer, but also of other tumours. It remains unsettled if gastric carcinoma (GC) should be included in this spectrum, especially when high-incidence countries for this tumour are considered.

Aims: To study GC characteristics in LS families and to compare them with a group of sporadic GC.

Methods: 25 patients with histological confirmation of GC, belonging to 20 LS families, were included in the present study. The families fulfilled: Amsterdam criteria (n=12); Bethesda criteria (n=2); Amsterdam criteria only if GC was considered (atypical LS – n=6). In the sporadic group, 58 consecutive patients with GC were included. Sex, age at GC diagnosis, tumour localization, histological type, differentiation and type of surgery were analyzed. In the LS group, mutational analysis for MLH1 and MSH2 was performed by DDGE/MLPA and direct sequencing.

Results: GC patients in LS were younger and in these cases GC was more frequently detected at earlier stages, and more frequently submitted to curative surgery (p=0.045). Signet-ring cell carcinoma was more common in sporadic GC, while mucinous carcinoma was more frequent in LS (p=0.014). Genetic diagnosis was inconclusive in all atypical LS families studied and positive in 73% of the classical LS families tested (p=0.02). Other tumours of the LS spectrum were more commonly found in patients from families with identified mutations (p=0.002) and in no cases from atypical LS families (p=0.009).

Conclusions: A subgroup of patients with GC and LS presented characteristics that strongly suggest GC inclusion in the LS tumour spectrum. In atypical LS families, the presence of GC does not seem to contribute for the diagnosis of this entity. It would be useful to find markers that could distinguish GC cases more likely to be associated with LS.

 

 

 

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(1) Serviço de Gastrenterologia, IPOLFG, EPE, Lisboa, Portugal.

(2) Serviço de Gastrenterologia, Hospital do Espírito Santo, Évora, Portugal.

(3) Clínica de Risco Familiar, IPOLFG, EPE, Lisboa, Portugal.

(4) C.I.P.M., IPOLFG, EPE, Lisboa, Portugal.

(5) Serviço de Anatomia Patológica, IPOLFG, EPE, Lisboa, Portugal.

 

Correspondência:

Isadora Alexandra da Luz Rosa

Serviço de Gastrenterologia do HESE

Largo Sr. da Pobreza

7000-811 Évora

Tel.: (+351) 266 740 100

e-mail: isaalr9@aeiou.pt

 

Recebido para publicação: 31/07/2007

Aceite para publicação: 17/04/2008