[Lynch syndrome: selection of families by microsatellite instability and immunohistochemistry].
BACKGROUND
Selection of patients with Lynch Syndrome (LS) for a genetic study involves the application of clinical criteria. To increase the rate of identification of mutations, the use of molecular studies as Microsatellite Instability (MSI) and Immunohistochemistry (IHC) in the tumor has been proposed.


OBJECTIVE
To demonstrate the usefulness of MSI and IHC in the detection of mutations in patients with LS.


METHODS
From our Familial Colorectal Cancer Registry, families suspected of LS were selected according to Amsterdam or Bethesda clinical criteria. Screening of germline mutations of MLH1, MSH2 and MSH6 genes was performed. In addition, analysis of MSI and IHC were performed in colorectal tumors.


RESULTS
A total of 35 families were studied (19 met Amsterdam and 16 met Bethesda criteria). Twenty one families harbored a germline alteration in MLH1, MSH2 or MSH6 (18 Amsterdam and 3 Bethesda). In these families, eighteen different alterations were found, 15 of which were mutations and 3 corresponded to variants of uncertain pathogenicity. On the other hand, 80% of the tumors showed positive microsatellite instability (27 MSI-high and 1 MSI-low), and immunohistochemical testing showed that 77% of tumors had the loss of a protein. Correlation between results of tumor molecular studies and the finding of germline nucleotide change showed that IHC and MSI predicted mutations in 81 and 100% of patients, respectively.


CONCLUSIONS
MSI and IHC can efficiently select patients with a high probability of carrying a mutation in DNA repair genes.
Unidad de Coloproctología, Laboratorio de Oncología y Genética Molecular, Chile.
Ana María
AM
Wielandt
Alejandro J
AJ
Zárate
Claudia
C
Hurtado
Paulina
P
Orellana
Karin
K
Alvarez
Eliana
E
Pinto
Luis
L
Contreras
Alejandro
A
Corvalán
Udo
U
Kronberg
Francisco
F
López-Köstner
D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability