+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Role of topoisomerase I and thymidylate synthase expression in sporadic colorectal cancer: associations with clinicopathological and molecular features

Role of topoisomerase I and thymidylate synthase expression in sporadic colorectal cancer: associations with clinicopathological and molecular features

Pathology, Research and Practice 210(2): 111-117

Topoisomerase I (Topo I) and thymidylate synthase (TS) are essential enzymes for the replication, transcription and repair of DNA, and are potential biomarkers in colorectal cancer (CRC). The aim of the study was to correlate the tissue expression of Topo I and TS in sporadic CRCs with relevant pathological and molecular features and patients' outcome. Topo I and TS expression was assessed by immunostaining in 112 consecutive primary CRCs. Increased expression of Topo I was found in 36% of tumors, preferentially rectal (50%) and with not otherwise specified (NOS) histology (44%). Topo I expression was associated with 18q allelic loss (LOH), (p=0.013), microsatellite stable phenotype (p=0.002) and normal expression of mismatch proteins hMLH1 and hMSH2 (p=0.0012 and p=0.02, respectively). High TS expression was found in 60% of tumors, more frequently in distal sites (62%) and with NOS histology (66%); no association with microsatellite instability was observed. Topo I seems to be involved in the chromosomal instability pathway of sporadic CRCs. Conversely, high TS expression is unlikely to affect the clinical behavior of microsatellite unstable CRCs.

(PDF emailed within 0-6 h: $19.90)

Accession: 055614977

Download citation: RISBibTeXText

PMID: 24332575

DOI: 10.1016/j.prp.2013.11.004

Related references

Associations between polymorphisms in the thymidylate synthase gene, the expression of thymidylate synthase mRNA and the microsatellite instability phenotype of colorectal cancer. Oncology Reports 11(4): 839-843, 2004

Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor. Virchows Archiv 454(6): 695-702, 2009

Topoisomerase-I, thymidylate synthase primary tumour expression and clinical efficacy of 5-FU/CPT-11 chemotherapy in advanced colorectal cancer patients. International Journal of Cancer 111(2): 252-258, 2004

Topoisomerase-1 and thymidylate synthase primary tumor expression as prognostic and predictive factors for response to CPT-11 in advanced colorectal cancer patients. European Journal of Cancer 37(Supplement 6): S308, October, 2001

Gene expression profiling: canonical molecular changes and clinicopathological features in sporadic colorectal cancers. World Journal of Gastroenterology 14(43): 6662-6672, 2008

Association between p53 expression and Bcl-2, P-glycoprotein, topoisomerase II alpha, thymidylate synthase and thymidine phosphorylase as potential therapeutic targets in colorectal cancer patients. Pakistan Journal of Biological Sciences 10(19): 3350-3355, 2009

Correlations of clinicopathological factors with protein expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase and orotate phosphoribosyltransferase in colorectal cancer. ChemoTherapy 56(2): 120-126, 2010

Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5-fluorouracil based chemotherapy treatment. Medical Oncology 31(2): 825-825, 2014

High thymidylate synthase expression is typical for sporadic MSI-H colorectal carcinoma. Polish Journal of Pathology 57(1): 29-33, 2006

Expression of dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase and thymidylate synthase in patients with primary colorectal cancer, and associations with site of first metastasis. Anticancer Research 32(6): 2277-2282, 2012

Associations between the cyclooxygenase-2 expression in circulating tumor cells and the clinicopathological features of patients with colorectal cancer. Journal of Cellular Biochemistry: -, 2018

Thymidylate synthase expression levels: a prognostic and predictive role in advanced colorectal cancer. Oncology Reports 14(3): 657-662, 2005

Prognostic value of thymidylate synthase, topoisomerase-1 and Ki-67 in advanced colorectal cancer patients on irinotecan and fluorouracil treatment. Zhonghua Zhong Liu Za Zhi 27(5): 312-315, 2005

Correlation between thymidylate synthase protein expression and gene polymorphism with clinicopathological parameters in colorectal carcinoma. International Journal of Surgical Pathology 17(3): 181-186, 2009

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer. Endocrine-Related Cancer 24(7): 299-307, 2017