HMSH6 immunohistochemistry in patients with clinical suspicion of Hereditary Non-Polyposis Colorectal Cancer.

Colorectal Cancer (HNPCC) occurs in hMLHl or hMSH2. Recent observations have shown that mutations at hMSl·I6 also involved. Aim of our study is to investigate the role of hMSH6 gene in HNPCC by imnohistochernisny.Materials and methods. 28 colorectal cancer patients with clinical diagnosis of HNPCC or suspected HNPCC were inelected. Immunoliistochemical studies of hMSH6, hMLl—Il and hMSH2 were carried out on paraflin-embedded tumoursamples. lmrm1noperoxidase—staining using diarninobenzidinc as chromogen was carried out with the NEX-ES,Automatic Staining System (Ventana). Mouse monoclonal antibodies to 11MLI-I1 and hMSI-12 proteins (6163-15 andGI29-1129, Pharmingen) were used at 1:40 dilution, mouse monoclonal antibody to hMSH6 protein (clone 44,Transduction Laboratories) was used at 1:2000 dilution. All tumour samples were tested for MSI. Results. Lack of bMSH6 expression was detected in 7 out of 28 tumors. 4 of them also showed absence of hMSH2expression All 7 patients (mean age 56.6 yrs) were affected by right-sided colon cancer, most trequently mucinous and MSI+. 3 patients were from HNPCC families fulfilling Amsterdam Criteria I or I1, 2 were diagnosed as having Muir- Torre syndrome (MTS), and 2 had a diagnosis of suspected HNPCC. An excess of extracolonic tumours was observed in ali the pedigrees but one. interestingly, in both MTS patients, colorectal cancers and sebaceous dermatologic lesionsif thowed the same immunohistochemical pattern. At the moment, the complete MMR gene sequencing has been performed for 3 out of the 7 patients. 2 IJMSH6 and l hMSH2 ramcshifl mutations were detected- Conclusions. l1MSH6 mutations could be characteristic of a subset of HNPCC families. Altered hMSH6 immunohistochemical expression (although often associated with lack of hMSH2 protein), MSI positivity, proximal ` lllcalization, later age at diagnosis and association with extracolonic tumours, all seem to be prognostic features for the presence of this genetic alteration.