title: Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor.
abstract: Colorectal carcinoma (CRC) is a heterogeneous disease with specific epidemiological, pathological, molecular, and clinical characteristics that depend on the location of the tumor relative to the splenic flexure. Thymidylate synthase (TS) is a major target of 5-fluorouracil-based chemotherapy for CRC and high expression of this enzyme in tumor cells can influence the effect of therapy. We examined differences in TS protein expression in nuclei of tumor cells between CRCs located proximal and distal to the splenic flexure. Nuclear TS was detected by immunohistochemistry with a TS 106 monoclonal antibody on tissue microarrays constructed from 269 CRCs. The median histological score of nuclear TS expression of all proximal tumors was two times higher (p = 0.0003) and in men three times higher (p = 0.00023) than that found in distal tumors. In multivariate analysis which included age, sex, Astler-Coller stage, histological grade, and site, only proximal location of the tumor was identified as an independent factor associated with higher TS expression (odds ratio 2.46, 95% confidence interval = 1.29-4.70, p = 0.0062). These results demonstrate significant differences in nuclear TS expression between proximal and distal cancers and suggest the potential importance of the site of the tumor for proper stratification of patients for chemotherapy.
authors.affiliation: Department of Oncological Surgery, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Violetta
authors.initials: V
authors.lastname: Sulzyc-Bielicka
authors.forename: Pawel
authors.initials: P
authors.lastname: Domagala
authors.forename: Ewa
authors.initials: E
authors.lastname: Majdanik
authors.forename: Maria
authors.initials: M
authors.lastname: Chosia
authors.forename: Dariusz
authors.initials: D
authors.lastname: Bielicki
authors.forename: Jozef
authors.initials: J
authors.lastname: Kladny
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kaczmarczyk
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Wenancjusz
authors.initials: W
authors.lastname: Domagala
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002467:Cell Nucleus / Q000201:enzymology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007420:Intestine, Large / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013940:Thymidylate Synthase
chemical_list: D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase