BMC Cancer 2BR2M0e0Cs2eC,aanrccerh article x Predominance of CIN versus MSI in the development of rectal cancer at young age Eva Fernebro*1, Britta Halvarsson2, Bo Baldetorp1 and Mef Nilbert1 Address: 1Department of Oncology, University Hospital, Lund, Sweden and 2Department of Pathology, University Hospital, Lund, Sweden E-mail: Eva Fernebro* - Eva.Fernebro@onk.lu.se; Britta Halvarsson - Britta.Halvarsson@skane.se; Bo Baldetorp - Bo.Baldetorp@onk.lu.se; Mef Nilbert - Mef.Nilbert@onk.lu.se *Corresponding author BioMed Central Open Access Published: 14 October 2002 BMC Cancer 2002, 2:25 This article is available from: http://www.biomedcentral.com/1471-2407/2/25 Received: 18 June 2002 Accepted: 14 October 2002 © 2002 Fernebro et al; licensee BioMed Central Ltd. This article is published in Open Access: verbatim copying and redistribution of this article are per- mitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Keywords: Rectal cancer, MSI, Flow cytometry, KRAS , p53, -catenin, MLH1 , MSH2 , Im- munohistochemistry, HNPCC Abstract Background: Development of proximal and distal colorectal cancers involve partly different mechanisms associated with the microsatellite instability (MSI) and the chromosomal instability (CIN) pathways. Colorectal cancers in patients under 50 years of age represent about 5% of the total number of tumors and have been associated with an increased frequency of MSI tumors. However, MSI and CIN may play different roles in the development of colon cancer and rectal cancer, and we have specifically investigated their contribution to the development of rectal cancer at young age. Methods: Thirty rectal cancers diagnosed before the age of 50 were characterized for DNA- ploidy, MSI, mutations of KRAS and CTNNB1 and immunohistochemical expression of p53, -catenin and of the mismatch repair (MMR) proteins MLH1 and MSH2. Results: DNA aneuploidy was detected in 21/30 tumors, KRAS mutations in 6 tumors, no mutations of CTNNB1 were detected but immunohistochemical staining for -catenin showed nuclear staining in 6 tumors, and immunohistochemical expression of p53 was detected in 18 tumors. MSI was detected in 3/30 tumors, all of which showed and immunohistochemical loss of staining for the MMR protein MSH2, which strongly indicates a phenotype associated with hereditary nonpolyposis colorectal cancer (HNPCC). Conclusions: MSI occurs only in a small fraction of the tumors from young patients with rectal cancer, but when present it strongly indicates an underlying HNPCC-causing mutation, and other mechanisms than HNPCC thus cause rectal cancer in the majority of young patients. Background Colorectal cancer represents 12% of the cancer cases in Sweden with about 5% of the patients being below 50 years of age [1]. Rectal cancer constitutes about 1/3 of the large bowel cancers and 5% of the patients are younger than 50 years of age at diagnosis. Tumor development at young age may be an indicator of hereditary cancer, such as hereditary nonpolyposis colorectal cancer (HNPCC), Page 1 of 8 (page number not for citation purposes)