Immunohistochemical evaluation of thymidylate synthase in gastric carcinoma using a new polyclonal antibody

Kuniyasu, Tetsuya; Nakamura, Takeshi; Tabuchi, Yoshiaki; Kuroda, Yoshikazu

doi:10.1002/(sici)1097-0142(19981001)83:7<1300::aid-cncr5>3.0.co;2-m

Cited by 51 publications

(18 citation statements)

References 18 publications

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“…For the same reason this significant difference in survival is of little clinical relevance. Improved survival in patients with low TS activity has been shown in patients with colorectal and breast cancer [21][22][23]40] and has been suggested for gastric cancer [26,28,29], although lack of correlation has also been reported [24,27]. Our study showed no difference in survival between patients with low and high TS expression.…”

Section: Discussionsupporting

confidence: 50%

“…This is in agreement with a recent study [26] showing no correlation of TS activity with the effect of adjuvant 5FU/Adriamycin chemotherapy in patients with gastric cancer. Two other studies, using different methodology, showed better survival in patients with low TS expression [26,28], while studies in colorectal cancer have shown that patients with high TS expression benefited more than low expressors by adjuvant 5-FU [22,23,39]. It has to be noted that the retrospective non-randomized analysis used in all three mentioned studies as well as ours is not the ideal way of evaluating the prognostic Table 4.…”

Section: Discussionmentioning

confidence: 77%

“…With identical methodology, our results are similar to those of Choi et al, who have published the only study with patients who had gastrectomy for gastric cancer. Three other studies, which included patients with gastric cancer, have reported survival benefit in patients with low TS expression, but different methods of assessment of TS expression were used [26,28,29]. Our sample may be inadequate to reach statistical significance, since studies, which showed prognostic significance of TS expression, included significantly higher number of patients [21][22][23]39].…”

Section: Discussionmentioning

confidence: 99%

“…One study showed a significant 5-year survival benefit in patients with stage IIIb with low TS expression [26], while the other study showed no benefit [27]. Finally, two studies including both treated and untreated patients suggested a survival benefit for patients with low TS expression [28,29]. Nevertheless, statistical significance was reached only in one of them [28].…”

Section: Introductionmentioning

confidence: 99%

“…Finally, two studies including both treated and untreated patients suggested a survival benefit for patients with low TS expression [28,29]. Nevertheless, statistical significance was reached only in one of them [28].…”

Section: Introductionmentioning

confidence: 99%

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DCC and TS protein expression in resected gastric cancer: A Hellenic Cooperative Oncology Group Study

et al. 2008

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AbstractThere is a high risk of relapse after resection of gastric cancer. We studied the prognostic significance of the deleted colorectal cancer (DCC) gene and thymidylate synthase (TS) protein expression after resection of gastric cancer. Protein expression in the primary tumor of 146 patients with serosal and/or lymph node involvement was studied immunohistochemically by using anti-DCC and anti-TS monoclonal antibodies. DCC expression was found in 69.9%, while low TS staining intensity (0+,1+) and focal staining (<25% of tumor cells stained) were found in 44.6% and 33.8%, respectively. Overall survival (OS) was significantly longer in patients with DCC (p=0.014) negative tumors. TS expression was not an independent prognostic factor. Lack of DCC expression was associated with significantly longer cause-specific survival (CSS) (p=0.040) after curative resection. In conclusion, DCC expression is an independent prognostic factor in patients undergoing resection of gastric cancer while TS expression was not associated with the prognosis in our study.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DCC and TS protein expression in resected gastric cancer: A Hellenic Cooperative Oncology Group Study

et al. 2008

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Prognostic significance of thymidylate synthase activity in bladder carcinoma

Mizutani

Wada

Ogawa

et al. 2001

Cancer

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BACKGROUND 5‐fluorouracil (5‐FU) is an anticancer agent clinically used against various cancers including bladder carcinoma. 5‐FU inhibits thymidylate synthase (TS) and blocks DNA synthesis. TS is the key enzyme in the catalysis of the methylation from deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate. Little is known about the significance of TS in bladder carcinoma. The authors investigated the activity of TS in 82 bladder cancers and prognostic significance of the levels of TS and/or activities of dihydropyrimidine dehydrogenase (DPD), an important enzyme in the degradation of 5‐FU. METHODS The levels of TS and DPD activities in nonfixed, fresh, frozen, bladder carcinoma and normal bladder specimens were determined biochemically by the FdUMP binding assay and the 5‐FU degradation assay, respectively. RESULTS The activity of TS was 10‐fold higher in bladder carcinoma compared with normal bladder. TS activity in muscle‐invasive bladder carcinoma was threefold higher than that in Ta and T1 cancer. In addition, the activity of TS in T1 bladder carcinoma was threefold higher than that in Ta cancer. The level of TS activity in Grade 3 bladder carcinoma was 4.5‐fold and 3.5‐fold higher than that in Grade 1 and Grade 2 cancers, respectively. Patients with Ta and T1 bladder carcinoma with low TS activity had a longer postoperative tumor‐free period than those with high activity in the 2‐year follow‐up. Patients with Ta and T1 bladder carcinoma with high or low TS activity were divided into four subgroups: high or low DPD activity subgroups. Patients with low TS activity and high DPD activity had the longest postoperative disease‐free period among the 4 subgroups during the 2‐year follow‐up. CONCLUSIONS To the authors' knowledge, the current study is the first study that demonstrated that the level of TS activity correlates with both the progression of the stage and the increase of the grade of bladder carcinoma and that elevated TS activity predicts early recurrence in Ta and T1 bladder carcinoma. These results suggested that elevated TS activity might have been associated with a higher chance of progression and recurrence of bladder carcinoma in the patients who participated in this study. Cancer 2001;92:510–8. © 2001 American Cancer Society.

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Significance of thymidylate synthase gene expression level in patients with adenocarcinoma of the lung

Hashimoto

Ozeki

Sato

et al. 2006

Cancer

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The objective of this case‐matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low‐dose dexamethasone (BiRd) vs. lenalidomide/low‐dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital‐Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention‐to‐treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very‐good‐partial‐response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time‐to‐progression (median 48.3 vs. 27.5 months, P = 0.071), and progression‐free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3‐year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3–4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case‐matchedanalysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

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Immunohistochemical evaluation of thymidylate synthase in gastric carcinoma using a new polyclonal antibody

Cited by 51 publications

References 18 publications

DCC and TS protein expression in resected gastric cancer: A Hellenic Cooperative Oncology Group Study

DCC and TS protein expression in resected gastric cancer: A Hellenic Cooperative Oncology Group Study

Prognostic significance of thymidylate synthase activity in bladder carcinoma

Significance of thymidylate synthase gene expression level in patients with adenocarcinoma of the lung

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