Thymidylate synthase expression and prognosis of patients with gastrointestinal cancers receiving adjuvant chemotherapy: a review

Formentini, A.; Henne‐Bruns, Doris; Kornmann, Marko

doi:10.1007/s00423-004-0510-y

Cited by 30 publications

(16 citation statements)

References 47 publications

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“…For adjuvant treatment, it is controversial whether TS levels measured in primary CRC predict clinical benefit from 5-FU-based treatment. In several studies, a high TS level was associated with poor postoperative outcome, independent of the Duke's stage (Kralovánszky et al, 2002;Formentini et al, 2004), and leading to poor DFS and OS in an adjuvant setting (Cascinu et al, 2001;Kralovánszky et al, 2002;Allegra et al, 2003;Popat et al, 2004;Broll et al, 2005). In contrast, other reports indicated that high TS is predictive of 5-FU treatment and patients with a high TS level may benefit from adjuvant 5-FU therapy (Edler et al, 2002;Kornmann et al, 2003).…”

Section: Discussionmentioning

confidence: 84%

Thymidylate Synthase Gene Polymorphism and Survival of Colorectal Cancer Patients Receiving Adjuvant 5-Fluorouracil

Sulżyc-Bielicka

Bielicki²,

Bińczak-Kuleta³

et al. 2013

Genetic Testing and Molecular Biomarkers

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Limited studies indicate a possible association of 5¢-UTR thymidylate synthase enhancer region polymorphism and treatment outcome in patients medicated with 5-fluorouracil (5-FU). The study was designed to verify the relationship in patients with colorectal cancer (CRC), a Polish population that received 5-FU-based adjuvant chemotherapy. The study analyzed 145 Astler-Coller B2 and C CRC patients. Genotyping for a variable number of tandem repeats and G to C single-nucleotide polymorphism in the 5¢-UTR of the thymidylate synthase (TS) gene was carried out. TS genotypes were classified into high expression (high TS) and low expression types (low TS). High TS was found in 22.8% of patients. The right-side tumors were more frequently associated with high TS than the left-side tumors ( p = 0.024). High TS was only found in 9.3% of rectal tumors, but in 29.7% of colon cancers ( p = 0.0042). Disease-free survival after 20 months (DFS 20) was longer in subjects with low TS than in high TS ( p = 0.043). Patients who underwent chemotherapy had longer DFS 20 in the low TS than in the high TS subgroup ( p = 0.051). The low TS was found to be an independent good prognostic factor for DFS 20 in the whole group as well as in the subgroup treated with chemotherapy ( p = 0.024 and p = 0.034, respectively). Patients with low TS did not show any differences in DFS 20 whether they were treated with adjuvant chemotherapy or not. Proximal CRC tumors are characterized by higher TS expression genotypes than distal tumors, and are at significantly greater risk of early recurrence during the first 20 months after surgery.

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Section: Discussionmentioning

confidence: 84%

Thymidylate Synthase Gene Polymorphism and Survival of Colorectal Cancer Patients Receiving Adjuvant 5-Fluorouracil

Sulżyc-Bielicka

Bielicki²,

Bińczak-Kuleta³

et al. 2013

Genetic Testing and Molecular Biomarkers

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“…In fact, several studies have reported a significant association between TS expression and survival in cancer patients who underwent curative resection without receiving chemotherapy. Formentini et al [40] demonstrated that high TS expression was associated with poor prognosis in patients with gastrointestinal cancer who underwent complete tumor resection but without adjuvant chemotherapy. In the current study, we found that patients with high intratumoral TS expression had a significantly worse prognosis than patients with low TS expression and that intratumoral TS expression was an independent prognostic factor in these patients.…”

Section: Discussionmentioning

confidence: 98%

Impact of intratumoral thymidylate synthase expression on prognosis after surgical resection for ampullary carcinoma

Kato

Murakami

Uemura

et al. 2011

Journal of Surgical Oncology

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“…Patients with low TS expression given adjuvant therapy appear to have a worse prognosis than with surgery alone [81]. This appears to be different from the situation in palliative 5-FU-based chemotherapy [82]. Patients with colon tumors exhibiting high-frequency microsatellite instability do not benefit from 5-FU-based chemotherapy [4].…”

Section: Expert Commentary and Five-year Viewmentioning

confidence: 99%

Effects of 5-fluorouracil adjuvant treatment of colon cancer

Kelder

Hospers

Plukker³

2006

Expert Review of Anticancer Therapy

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Since the late 1980s and early 1990s, 5-fluorouracil-based chemotherapy has been the standard adjuvant treatment for Stage III colon cancer. After the initial introduction of 5-fluorouracil in standard treatment protocols, several changes have been made based on results of randomized studies on various treatment regimens, including new cytotoxic agents. In Stage II patients, the role of adjuvant chemotherapy is debatable. However, there might be a role for adjuvant treatment in certain high-risk patients. Following a search of the Medline database, the results of randomized studies on 5-fluorouracil-based adjuvant therapy are reviewed, and future therapeutic options are discussed.

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Thymidylate synthase expression and prognosis of patients with gastrointestinal cancers receiving adjuvant chemotherapy: a review

Cited by 30 publications

References 47 publications

Thymidylate Synthase Gene Polymorphism and Survival of Colorectal Cancer Patients Receiving Adjuvant 5-Fluorouracil

Thymidylate Synthase Gene Polymorphism and Survival of Colorectal Cancer Patients Receiving Adjuvant 5-Fluorouracil

Impact of intratumoral thymidylate synthase expression on prognosis after surgical resection for ampullary carcinoma

Effects of 5-fluorouracil adjuvant treatment of colon cancer

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