Cyclooxygenase-2 expression in FAP patients carrying germ line MYH mutations.
Familial adenomatous polyposis (FAP) is an autosomal condition caused by inherited mutations in the adenomatous polyposis coli (APC) or in the MYH genes. Clinical trials have established that nonsteroidal anti-inflammatory drugs (NSAID) are effective in preventing the development as well as reducing the size and decreasing the number of adenomas in FAP patients. Our aim was to evaluate the cyclooxygenase-2 (COX-2) expression in surgical specimens from patients with no evidence of germ line APC mutations but carrying germ line MYH mutations. COX-2 expression was evaluated through immunohistochemical and mRNA analysis in carcinomas, adenomas, and healthy mucosa from six patients carrying germ line biallelic MYH mutations. A modulation of COX-2 expression from adenoma (lower level) to carcinoma (higher level) was observed in all patients by both immunohistochemical and mRNA analysis. Moreover, patients with MYH mutations showed a weak COX-2 expression in the whole colorectal mucosa, as for classic FAP patients carrying germ line APC mutations. All together, our data suggest that biallelic MYH patients might benefit from NSAID treatment, because in these patients COX-2 is overexpressed in the whole colorectal mucosa, a finding possibly related to the interplay between COX-2 and APC protein being the APC gene a common target of mutations in MYH patients.
Frattini
Milo
M
Department of Experimental Oncology and Unit of Experimental Molecular Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via G. Venezian 1, 20133 Milan, Italy.
Carnevali
Ileana
I
Signoroni
Stefano
S
Balestra
Debora
D
Moiraghi
Maria Luisa
ML
Radice
Paolo
P
Varesco
Liliana
L
Gismondi
Viviana
V
Ballardini
Giovanni
G
Sala
Paola
P
Pierotti
Marco A
MA
Pilotti
Silvana
S
Bertario
Lucio
L
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D051546:Cyclooxygenase 2; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase