title: Role of topoisomerase I and thymidylate synthase expression in sporadic colorectal cancer: associations with clinicopathological and molecular features.
abstract: 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.
authors: Center for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy. Electronic address: cinzia.azzoni@unipr.it.
authors: Cinzia
authors: C
authors: Azzoni
authors: Center for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy.
authors: Lorena
authors: L
authors: Bottarelli
authors: Department of Surgical Sciences, School of Medicine, University Hospital of Parma, Parma, Italy.
authors: Stefano
authors: S
authors: Cecchini
authors: Department of Surgical Sciences, School of Medicine, University Hospital of Parma, Parma, Italy.
authors: Antonio
authors: A
authors: Ziccarelli
authors: Center for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy.
authors: Nicoletta
authors: N
authors: Campanini
authors: Center for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy.
authors: Cesare
authors: C
authors: Bordi
authors: Department of Surgical Sciences, School of Medicine, University Hospital of Parma, Parma, Italy.
authors: Leopoldo
authors: L
authors: Sarli
authors: Center for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy.
authors: Enrico Maria
authors: EM
authors: Silini
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D043171:Chromosomal Instability / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D013940:Thymidylate Synthase; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human
keywords: 18qLOH; Chromosomal instability; Colorectal cancer; Thymidylate synthase; Topoisomerase I