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Correlation Between Thymidylate Synthase Protein Expression and Gene Polymorphism with Clinicopathological Parameters in Colorectal Carcinoma

Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil

André Almeida Schenka, MD, PhD

Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil

Paulo Latuff Filho, PhD

Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil

Helvia Nascimento, MD, PhD

Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil

Carmen Silvia Passos Lima, MD, PhD

Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil

Miriam Aparecida Silva Trevisan, MD, PhD

Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil

José Vassallo, MD, PhD

Laboratory of Investigative and Molecular Pathology, State University of Campinas Medical School, Campinas, São Paulo, Brazil, vassallomeister{at}gmail.com

5-Fluorouracil (5-FU) represents the basis of chemotherapy for colorectal carcinoma, inhibiting thymidylate synthase (TS), an essential enzyme for DNA replication. Previous studies have associated high TS protein expression by tumor cells with poor outcome of patients with colorectal carcinoma, but others have refuted these findings. In view of the potential role of TS as predictive parameter and the lack of consensus in the literature, the present study compared 2 methods: protein expression and gene polymorphism, correlating them with clinicopathological findings. Immunohistochemical detection of TS in tumor cells and detection of gene polymorphism in the blood were performed in 32 patients with colorectal carcinoma treated with 5-FU. No correlation was found between TS protein expression and gene polymorphism. Neither method correlated with survival, tumor staging, and tumor histological grading. This result possibly reflects a complex tumor response to 5-FU therapy, where TS is just one of the involved proteins.

Key Words: thymidylate synthase • gene polymorphism • immunohistochemistry • prognosis • colorectal carcinoma • polymerase chain reaction

This version was published on June 1, 2009

International Journal of Surgical Pathology, Vol. 17, No. 3, 181-186 (2009)
DOI: 10.1177/1066896908330480


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