Expression of thymidylate synthase, orotate phosphoribosyltransferase and dihydropyrimidine dehydrogenase in thymic epithelial tumors

Kaira, Kyoichi; Serizawa, Masakuni; Koh, Yasuhiro; Miura, Satoru; Kaira, Rieko; Abe, Masato; Nakagawa, Kazuo; Ohde, Yasuhisa; Okumura, Takehiro; Murakami, Haruyasu; Tsuya, Asuka; Nakamura, Yukiko; Naito, Tateaki; Takahashi, Toshiaki; Kondo, Haruhiko; Nakajima, Takashi; Endo, Masahiro; Yamamoto, Nobuyuki

doi:10.1016/j.lungcan.2011.04.001

Cited by 20 publications

(27 citation statements)

References 28 publications

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“…Several early reports on thymic epithelial neoplasms detected p53 immunoreactivity in 33.3-100% of cases [7,22,[47][48][49][50]. Mutational studies of this gene are rare.…”

Section: Tumor Suppressor Genesmentioning

confidence: 99%

Molecular aspects of thymic carcinoma

2012

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“…Several early reports on thymic epithelial neoplasms detected p53 immunoreactivity in 33.3-100% of cases [7,22,[47][48][49][50]. Mutational studies of this gene are rare.…”

Section: Tumor Suppressor Genesmentioning

confidence: 99%

Molecular aspects of thymic carcinoma

2012

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“…They reported three patients who received S-1 therapy: one of the tumors with high TS expression showed a good response, whereas that with hypo TS expression showed stable disease and progressive disease. Two cases with high OPRT expression showed good responses (PR and SD) [1]. We have described three cases of patients who received S-1 therapy; the tumor with high TS and OPRT expression, especially OPRT expression, showed a remarkable response.…”

Section: Discussionmentioning

confidence: 90%

“…Recently, Kaira et al [1] summarized 56 cases of thymic tumors, of which 17 were thymic carcinomas; they found a significant correlation between immunohistochemical expressions of TS, DPD, and OPRT, and the World Health Organization (WHO) International Histological Classification of Tumors grade of malignancy. Other than this report, there have been very few reports of thymic carcinoma patients who were treated with S-1 therapy, and no reports have described the details of immunohistochemical staining for TS, DPD, and OPRT and the effects of S-1 treatment.…”

Section: Introductionmentioning

confidence: 99%

Better efficacy of S-1 treatment for thymic carcinoma: case report and review of the literature

et al. 2012

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Primary thymic carcinoma is a rare tumor of the thymus gland. The role of chemotherapy in treating advanced thymic carcinoma is unclear. It has recently been reported that thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) expression may be important factors when predicting the effectiveness of 5-fluorouracil-based chemotherapy (Kaira et al., 74:419-425, 2011). In this report, we describe three cases in which S-1 or S-1 combination treatment was given as second-line therapy for thymic carcinoma, and examine the relationships between the immunohistochemical expression of TS, DPD, and OPRT and treatment effectiveness. There were no deaths due to toxicity. Two patients achieved partial remission (PR), and one patient achieved stable disease (SD). These results suggest that S-1 is a safe and promising regimen for thymic carcinoma. Immunohistochemical staining for OPRT expression tended to be stronger in the two PR cases than in the SD case. Based on the present results, it appears that S-1 may be useful for treating unresectable thymic carcinoma, and that OPRT expression may predict the response to S-1 treatment. Further clinical studies are needed to confirm these findings.Keywords Thymic carcinoma Á S-1 Á Thymidylate synthase (TS) Á Dihydropyrimidine dehydrogenase (DPD) Á Orotate phosphoribosyltransferase (OPRT)

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“…However, the relationship between the response to S-1 or 5-FU and the expression level of TS for patients with thymic epithelial tumors remains unclear. Here, we immunohistochemically investigated the expression of TS using biopsy tissue sample according to the procedures described in a previous report [12]. In our case, the immunohistochemical examination revealed a low TS protein expression (fig.…”

Section: Discussionmentioning

confidence: 96%

“…In various human neoplasms, the response to a 5-FU-based regimen is known to be higher in groups with low TS activity than in those with high TS activity [11]. We had already described that the expression of TS was significantly related to the grade of malignancy in thymic epithelial tumors, and TS expression within TC may play a crucial role in pathogenesis and tumor progressiveness [12]. In TC patients, TS was highly expressed and the high expression of TS was identified as a negative predictor.…”

Section: Discussionmentioning

confidence: 99%

Dramatic Response of S-1 Administration to Chemorefractory Advanced Thymic Cancer

et al. 2014

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Thymic cancer (TC) is a rare malignancy in thoracic tumors, and there has been no standard therapeutics for advanced or relapsed patients. The clinical significance of second-line or beyond chemotherapy for platinum refractory advanced TC remains unclear. Here, we present the experience of a patient with TC showing a complete response to S-1 as third-line chemotherapy. A 54-year-old female with TC was treated with carboplatin plus paclitaxel and thoracic radiotherapy as first-line chemoradiotherapy and amrubicin as second-line chemotherapy. After 3 cycles of amrubicin administration, the metastatic hepatic lesions revealed a markedly progressive disease. A single agent of S-1 was administered as sequencing chemotherapy. After 2 cycles of S-1, the patient achieved a complete remission of multiple metastatic sites. There was evidence of immunohistochemical staining of a low thymidylate synthase (TS) expression. The expression of TS may be closely associated with the efficacy of S-1 in patients with TC.

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Expression of thymidylate synthase, orotate phosphoribosyltransferase and dihydropyrimidine dehydrogenase in thymic epithelial tumors

Cited by 20 publications

References 28 publications

Molecular aspects of thymic carcinoma

Molecular aspects of thymic carcinoma

Better efficacy of S-1 treatment for thymic carcinoma: case report and review of the literature

Dramatic Response of S-1 Administration to Chemorefractory Advanced Thymic Cancer

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