AIMS: Thymidylate synthase (TS) and tumor suppressor p53 are two proteins with an influence on tumor resistance to radio-chemotherapy that is well known. For this reason we tested the effect of TS and p53 expression on clinical outcome (tumor recurrence and survival) in patients after curative tumor resection, especially in patients who received adjuvant radio-chemotherapy. PATIENTS AND METHODS: A total of 120 patients with colorectal cancer were included in the study. A curative resection was possible in 83 patients, and 30 of this group received adjuvant therapy. For the immunohistochemical staining of tumor specimens, monoclonal antibody (mAb) TS 106 against TS and mAb DO-1 against p53 protein were used. TS positivity was defined as a moderate to high staining intensity in the cytoplasma of cells and p53 positivity as nuclear staining of tumor cells in >10% of these cells. RESULTS: Thymidylate synthase immunoreactivity was found in 59% of all cases and p53 staining in 51%. No relation between clinicopathological features and p53 expression was found in contrast to TS expression, where a highly significant association of TS-positive cases with tumor invasion (pT) was observed. Curatively resected patients with a TS-positive tumor developed tumor recurrence/distant metastases significantly more often than TS negative tumors. The same result was found when comparing p53-positive with p53-negative tumors and TS+/p53+ with TS-/p53- tumors. TS expression was highly significantly associated with poor survival and was the strongest independent prognostic factor in multivariate analysis, followed by lymph node status. CONCLUSION: Thymidylate synthase expression seems to be an independent prognostic factor and a possible predictor of tumor recurrence in patients with colorectal cancer.
AIMS: Thymidylate synthase (TS) and tumor suppressor p53 are two proteins with an influence on tumor resistance to radio-chemotherapy that is well known. For this reason we tested the effect of TS and p53 expression on clinical outcome (tumor recurrence and survival) in patients after curative tumor resection, especially in patients who received adjuvant radio-chemotherapy. PATIENTS AND METHODS: A total of 120 patients with colorectal cancer were included in the study. A curative resection was possible in 83 patients, and 30 of this group received adjuvant therapy. For the immunohistochemical staining of tumor specimens, monoclonal antibody (mAb) TS 106 against TS and mAb DO-1 against p53 protein were used. TS positivity was defined as a moderate to high staining intensity in the cytoplasma of cells and p53 positivity as nuclear staining of tumor cells in >10% of these cells. RESULTS:Thymidylate synthase immunoreactivity was found in 59% of all cases and p53 staining in 51%. No relation between clinicopathological features and p53 expression was found in contrast to TS expression, where a highly significant association of TS-positive cases with tumor invasion (pT) was observed. Curatively resected patients with a TS-positive tumor developed tumor recurrence/distant metastases significantly more often than TS negative tumors. The same result was found when comparing p53-positive with p53-negative tumors and TS+/p53+ with TS-/p53- tumors. TS expression was highly significantly associated with poor survival and was the strongest independent prognostic factor in multivariate analysis, followed by lymph node status. CONCLUSION:Thymidylate synthase expression seems to be an independent prognostic factor and a possible predictor of tumor recurrence in patients with colorectal cancer.
Authors: H J Lenz; K D Danenberg; C G Leichman; B Florentine; P G Johnston; S Groshen; L Zhou; Y P Xiong; P V Danenberg; L P Leichman Journal: Clin Cancer Res Date: 1998-05 Impact factor: 12.531
Authors: T Takenoue; H Nagawa; K Matsuda; S Fujii; M E Nita; K Hatano; J Kitayama; T Tsuruo; T Muto Journal: Ann Surg Oncol Date: 2000-04 Impact factor: 5.344
Authors: C G Leichman; H J Lenz; L Leichman; K Danenberg; J Baranda; S Groshen; W Boswell; R Metzger; M Tan; P V Danenberg Journal: J Clin Oncol Date: 1997-10 Impact factor: 44.544
Authors: S W Lowe; S Bodis; A McClatchey; L Remington; H E Ruley; D E Fisher; D E Housman; T Jacks Journal: Science Date: 1994-11-04 Impact factor: 47.728
Authors: G J Peters; C L van der Wilt; B van Triest; G Codacci-Pisanelli; P G Johnston; C J van Groeningen; H M Pinedo Journal: Eur J Cancer Date: 1995 Jul-Aug Impact factor: 9.162
Authors: H J Lenz; C G Leichman; K D Danenberg; P V Danenberg; S Groshen; H Cohen; L Laine; P Crookes; H Silberman; J Baranda; Y Garcia; J Li; L Leichman Journal: J Clin Oncol Date: 1996-01 Impact factor: 44.544
Authors: A Paradiso; G Simone; S Petroni; B Leone; C Vallejo; J Lacava; A Romero; M Machiavelli; M De Lena; C J Allegra; P G Johnston Journal: Br J Cancer Date: 2000-02 Impact factor: 7.640
Authors: Eliane C M Zeestraten; Anne Benard; Marlies S Reimers; Philip C Schouten; Gerrit J Liefers; Cornelis J H van de Velde; Peter J K Kuppen Journal: Biomark Cancer Date: 2013-07-04