Loss of heterozygosity at 18q21 is indicative of recurrence and therefore poor prognosis in a subset of colorectal cancers

Adjuvant therapies are increasingly used in colorectal cancers for the prevention of recurrence. These therapies have side-effects and should, thus, be used only if really beneficial. However, the development of recurrence cannot be predicted reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus based only on the primary stage of the cancer. Loss of heterozygosity (LOH) in the long arm of chromosome 18 is suggested to be related to poor survival and possibly to the development of metastases. We studied the value of LOH at 18q21 as a marker of colorectal cancer prognosis, association with clinicopathological variables, tumour recurrence and survival of the patients. Of the 255 patients studied, 195 were informative as regards LOH status when analysed in primary colorectal cancer specimens using the polymerase chain reaction (PCR) and fragment analysis. LOH at 18q21 was significantly associated with the development of recurrence (P= 0.01) and indicated poor survival in patients of Dukes' classes B and C, in which most recurrences (82%) occurred. An increased rate of tumour recurrence is the reason for poor survival among patients with LOH at 18q21 in primary cancer. These patients are a possible target group for recurrence-preventing adjuvant therapies. © 1999 Cancer Research Campaig

Infrequent mutation of the tumour-suppressor gene Smad4 in early-stage colorectal cancer

Smad4 is a candidate tumour-suppressor gene identified recently on chromosome 18q21.1. Both alleles are inactivated in nearly one-half of pancreatic carcinomas, but its role in the tumorigenesis of other tumours is still unknown. The aim of this study was to investigate the potential involvement of the Smad4 locus in early-stage colorectal cancers (stages I–III) in tumour samples from a randomised multicentre trial. Of a large collection of DNA samples, 73 with a loss of one allele of the Smad4 gene were analysed for the presence of point mutations in the remaining gene. Patients, from whom biopsies were isolated, were part of a previous randomised multicentre study of the Swiss Group for Clinical Cancer Research on the benefit of adjuvant chemotherapy (SAKK study 40/81). Mutation analysis was restricted to the highly conserved C-terminal domain (exons 8, 9, 10 and 11) of Smad4, using PCR and single-strand conformational variant analysis. Two of the 73 patients (3%) with loss of one allele of Smad4 had a point mutation in the remaining allele. These results indicate that whereas Smad4 point mautations are prevalent in pancreatic carcinoma, they are infrequent in early stages (I–III) of colorectal cancer