[Need of new clinical criteria for the identification of genetic Lynch syndrome].
BACKGROUND
Surveillance programs in families with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), which is an autossomal dominant disease, decrease colorectal carcinoma mortality. There are multiple clinical criteria for the identification of these families, mainly: the Amsterdam Criteria (ACI), the modified Amsterdam Criteria (ACII) and the Bethesda Guidelines (BG).


OBJECTIVE
To correlate, in families with HNPCC, the clinical criteria with the probability of detecting a germ-line mutation in MLH1, MSH2 and MSH6 mismatch repair genes.


METHODS
We included 92 affected patients belonging to different families. Clinical criteria leading to HNPCC diagnosis were evaluated. Germ-line mutations in MLH1, MSH2 and MSH6 genes were performed by DGGE/MLPA and direct sequencing.


RESULTS
Germ-line mutations were detected in 54/92 (59%) families, 30 in MLH1, 23 in MSH2 and 1 in MSH6. Germ-line mutation detection was significantly lower in ACI without age criteria (0%), when compared to: ACI (60%), ACII (62%), ACII without age criteria (67%) and BG (61%).


CONCLUSIONS
The classic, modified AC and BG allowed the detection of an identical percentage of families with mutation positive HNPCC. The absence of the age criteria in the ACI makes the HNPCC diagnosis highly unlikely. Simpler and uniform criteria should be elaborated, to allow a homogeneous identification of families with HNPCC.
Sousa
Rita
R
Serviço de Gastrenterologia, Centro de Investigação de Patologia Molecular, Clínica de Risco Familiar, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa.
Lage
Pedro
P
Ferreira
Sara
S
Claro
Isabel
I
Francisco
Inês
I
Filipe
Bruno
B
Albuquerque
Cristina
C
Suspiro
Alexandra
A
Rodrigues
Paula
P
Nobre-Leitão
Carlos
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation