+ 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

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Endocrine-Related Cancer 24(7): 319-327

Topoisomerase II alpha (TOP2A) and thymidylate synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of TOP2A and TS mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and protein expression was assessed by immunohistochemistry in a subset of 39 tumors. Ninety-two patients were radically resected for stage II-III disease and 38 of them received adjuvant mitotane. Twenty-six patients with metastatic disease received the EDP-M (etoposide, doxorubicin, Adriamycin, cisplatin plus mitotane). TOP2A and TS expression in ACC tissue was directly correlated with the clinical data. Both markers were not associated with either disease free survival (DFS) or overall survival (OS) in multivariate analyses and failed to be associated to mitotane efficacy. Disease response or stabilization to EDP-M treatment was observed in 12/17 (71%) and 1/9 (11%) patients with high and low TOP2A expressing tumors (P = 0.0039) and 9/13 (69%) and 4/13 (31%) patients with high and low TS expressing ACC, respectively (P = 0.049). High TOP2A expression was significantly associated with longer time to progression (TTP) after EDP-M. TOP2A and TS proteins assessed by immunohistochemistry significantly correlated with mRNA expression. Immunohistochemical TOP2A expression was associated with a non-significant better response and longer TTP after EDP-M. TOP2A and TS were neither prognostic nor predictive of mitotane efficacy in ACC patients. The predictive role of TOP2A expression of EDP-M activity suggests a significant contribution of Adriamycin and etoposide for the efficacy of the EDP scheme.

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

Accession: 060408691

Download citation: RISBibTeXText

PMID: 28432084

DOI: 10.1530/ERC-17-0095

Related references

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, 2015

The pemetrexed-containing treatments in the non-small cell lung cancer is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis. Bmc Cancer 14: 205, 2014

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, 2001

Prognostic implications of the expression of erbB2, topoisomerase II alpha and thymidylate synthase in metastatic gastric cancer after fluorouracil-based therapy. Japanese Journal of Clinical Oncology 34(12): 727-732, 2005

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

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

Combination of 5-fluorouracil and irinotecan on modulation of thymidylate synthase and topoisomerase I expression and cell cycle regulation in human colon cancer LoVo cells: clinical relevance. Clinical Colorectal Cancer 2(3): 182-188, 2002

The correlation between thymidylate synthase expression and cytotoxicity of 5-fluorouracil in human cancer cell lines: study using polyclonal antibody against recombinant human thymidylate synthase. Gan to Kagaku Ryoho. Cancer and ChemoTherapy 24(6): 705-712, 1997

Polymorphism of the thymidylate synthase gene and thymidylate synthase levels in colon cancer cell lines and different tissues of colorectal cancer patients. Nucleosides, Nucleotides and Nucleic Acids 23(8-9): 1381-1384, 2004

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

Thymidylate synthase, topoisomerase-1 and microsatellite instability: relationship with outcome in mucinous colorectal cancer treated with fluorouracil. Anticancer Research 33(10): 4611-4617, 2013

Topoisomerase I but not thymidylate synthase is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy. Bmc Cancer 9: 339, 2010

Polymorphisms of folate pathway enzymes (methylenetetrahydrofolate reductase and thymidylate synthase) and their relationship with thymidylate synthase expression in human astrocytic tumors. Dna and Cell Biology 31(1): 57-66, 2012

Expression of topoisomerase II, catalase, metallothionein and thymidylate-synthase in human squamous cell lung carcinomas and their correlation with doxorubicin resistance and with patients' smoking habits. Carcinogenesis 13(11): 1947-1950, 1992