Presence of activating KRAS mutations correlates significantly with expression of tumour suppressor genes DCN and TPM1 in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development.</p> <p>Methods</p> <p>We used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the <it>KRAS </it>mutation was investigated.</p> <p>Results</p> <p>We detected significant previously undescribed underexpression in CRC for genes <it>SLC26A3</it>, <it>TPM1 </it>and <it>DCN</it>, with a suggested tumour suppressor role. We also describe the correlation between <it>TPM1 </it>and <it>DCN </it>expression and the presence of <it>KRAS </it>mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the <it>TPM1 </it>gene in one case of CRC, but no deletions of <it>DCN </it>and <it>SLC26A3 </it>were found.</p> <p>Conclusion</p> <p>Our study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the <it>TPM1 </it>gene in a case of CRCs without <it>KRAS </it>mutations, showing that <it>TPM1 </it>might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the <it>TPM1 </it>gene. On the other hand, the correlation of <it>DCN </it>underexpression with the presence of <it>KRAS </it>mutations suggests that <it>DCN </it>expression is affected by the presence of activating <it>KRAS </it>mutations, lowering the amount of the important tumour suppressor protein decorin.</p

Results of rectal cancer treatment

Background: In Slovenia the incidence of colorectal cancer is growing rapidly. In 2000 591 new cases of colon cancer and 503 new cases of rectal cancer were registered. Our study compares results of two groups of patients with rectal cancer.Methods: In the period from January 1, 1991, to December 31, 2000, 528 patients with rectal carcinoma underwent resection. We divided them in two groups, one operated in the first 5-year and the other in later 5-year period. 5-year survival was estimated by means of Kaplan-Meier statistical analysis. Patients who died within 30 days after the operation were censored. Differences in survival curves between both groups were assessed by the log rank test.Results: We resected 528/591 (90.6 %) patients. R0 resection was performed in 431 (81.6 %) patients, R1 in 13 (2.5 %), and R2 in 84 (15.9 %) patients. Postoperative mortality rate in resected patients was 3.6 % (19/528), in the group with paliative operations was 12.7 % (7/55). Overall five-year survival rate was 52.4 % for rectal cancer. Five-year survival rate for the patients with radical resection (R0) was 59.5 %.Conclusions: 5-year survival for R0-resected patients with rectal cancer was in the period from 1996 to 2000 statistically significantly better compared with the period from 1991 to 1995 (63 % vs. 55 %) (p = 0.03627) in stage III (p = 0.01663).</p