title: E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.
abstract: The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.
authors.affiliation: Department of Clinical Oncology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Violetta
authors.initials: V
authors.lastname: Sulzyc-Bielicka
authors.affiliation: Department of Pathology, Pomeranian Medical University, Unii Lubelskiej 1, 71-252, Szczecin, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Domagala
authors.affiliation: Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Bielicki
authors.affiliation: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.affiliation: Department of Oncology, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rogowski
authors.affiliation: Department of Pathology, Pomeranian Medical University, Unii Lubelskiej 1, 71-252, Szczecin, Poland. wenek@pum.edu.pl.
authors.forename: Wenancjusz
authors.identifier: http://orcid.org/0000-0002-6647-9072
authors.initials: W
authors.lastname: Domagala
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016130:Immunophenotyping / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D013940:Thymidylate Synthase; D005472:Fluorouracil
keywords: 5FU-based therapy; Colorectal cancer; E2F1; Thymidylate synthase
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