Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis.
OBJECTIVE
MYH-associated polyposis is a recently described, autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. There are only few immunohistochemical studies of the MYH protein. We investigated the expression pattern of the MYH protein to evaluate whether a immunohistochemical approach could be used in clinical practice to screen patients for germline mutations in the MYH gene.


METHODS
The expression of MYH, MSH2, MLH1, and MSH6 proteins was studied by immunohistochemistry in 20 samples (colorectal adenomas or cancer) from 18 patients with biallelic MYH mutation, in 11 samples from patients with germline adenomatous polyposis coli (APC) mutations, in 20 samples from patients with sporadic colorectal cancers, and in 10 samples from patients with normal colonic mucosa without malignancies.


RESULTS
In all cases the mismatch repair proteins were expressed normally. Nuclear and cytoplasmic immunoreactivity for the MYH protein were observed in normal colorectal mucosa, in sporadic colorectal carcinomas, and in adenomas and carcinomas from patients carrying APC germline mutations. Adenomas and carcinomas from patients with MYH biallelic mutation showed a different pattern of expression: a strong granular cytoplasmic staining was observed without any nuclear expression. The same immunophenotype was observed in the surrounding normal mucosa.


CONCLUSIONS
Patients with biallelic MYH mutations showed disappearance of staining from the nucleus, and segregation of immunoreactivity in the cytoplasm, both in neoplastic and surrounding healthy mucosa. Because this pattern of expression seems to be specific for biallelic mutations, it follows that immunohistochemistry might be used in clinical practice to screen patients at risk for MYH-associated polyposis.
Di Gregorio
Carmela
C
Division of Pathology, Hospital of Carpi, Modena, Italy.
Frattini
Milo
M
Maffei
Stefania
S
Ponti
Giovanni
G
Losi
Lorena
L
Pedroni
Monica
M
Venesio
Tiziana
T
Bertario
Lucio
L
Varesco
Liliana
L
Risio
Mauro
M
Ponz de Leon
Maurizio
M
D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics*; D045647:DNA Glycosylases / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male
D004247:DNA; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase