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Published in: Journal of Cardiothoracic Surgery 1/2016

Open Access 01-12-2016 | Research article

Tumor-related gene expression levels in thymic carcinoma and Type B3 thymoma

Authors: Yoko Karube, Satoru Kobayashi, Sumiko Maeda, Tetsu Sado, Hiromi Ishihama, Masayuki Chida

Published in: Journal of Cardiothoracic Surgery | Issue 1/2016

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Abstract

Background

Thymic carcinoma (TC) is a rare type of malignant neoplasm that develops in the anterior mediastinum and associated with poor prognosis. Type B3 thymoma (B3) occasionally demonstrates malignant tumor characteristics, especially in the advanced stage. We investigated the expressions of tumor-related genes in resected TC and B3 specimens.

Methods

TC and B3 specimens resected from 1999 through 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg’s tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of cancer, data from lung cancer (LC) cases in our database were also examined.

Results

The gene expression levels of thymidylate synthase were significantly higher in TC and B3 as compared to LC specimens (p < 0.02), while no difference were observed between TC and B3 tumors. The ratio of folypolyglutamyl synthase (FPGS) to gamma-glutamyl hydrolase (GGH) mRNA was significantly lower in TC than in B3 (p < 0.05), with lower FPGS/GGH in those tumors related to overall survival. Also, the gene expression of vascular endothelial growth factor (VEGF) was significantly higher in TC as compared to B3 (p = 0.04), with higher VEGF gene expression in TC and B3 specimens related to overall survival of affected patients. Epidermal growth factor receptor (EGFR) expression was significantly higher in B3 as compared to both TC and LC specimens (p < 0.01). However, there were no EGFR gene mutations detected in any of the specimens.

Conclusions

These results indicate that elevated expressions of the tumor-related genes FPGS/GGH and VEGF are correlated with malignancy of TC and B3 tumors. Additional examinations will be necessary to investigate their chemosensitivity.
Literature
1.
go back to reference Shields TW. Thymic tumors. In: Shields TW, Locicero III J, Reed CE, Feins RH, editors. General Thoracic Surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2323–62. Shields TW. Thymic tumors. In: Shields TW, Locicero III J, Reed CE, Feins RH, editors. General Thoracic Surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 2323–62.
2.
go back to reference Müller-Hermelink HK, Möler P, Engel P, Menestrina F, Kuo TT, Shimosato Y, et al. Thymomas. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press; 2004. p. 148–53. J Thorac Cardiovasc Surg 2007,134:619–623. Müller-Hermelink HK, Möler P, Engel P, Menestrina F, Kuo TT, Shimosato Y, et al. Thymomas. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press; 2004. p. 148–53. J Thorac Cardiovasc Surg 2007,134:619–623.
3.
go back to reference Serpico D, Trama A, Haspinger ER, Agustoni F, Botta L, Berardi R, et al. Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors. Ann Oncol. 2015;26:838–47.CrossRefPubMed Serpico D, Trama A, Haspinger ER, Agustoni F, Botta L, Berardi R, et al. Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors. Ann Oncol. 2015;26:838–47.CrossRefPubMed
4.
go back to reference Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Eng J Med. 2006;355:983–91.CrossRef Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Eng J Med. 2006;355:983–91.CrossRef
5.
go back to reference Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007;25:2747–54.CrossRefPubMed Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007;25:2747–54.CrossRefPubMed
6.
go back to reference Kuramochi H, Hayashi K, Uchida K, Miyakura S, Shimizu D, Vallbohmer D, et al. Vascular endothelial growth factor messenger RNA expression level is preserved in liver metastases compared with corresponding primary colorectal cancer. Clin Cancer Res. 2006;12:29–33.CrossRefPubMed Kuramochi H, Hayashi K, Uchida K, Miyakura S, Shimizu D, Vallbohmer D, et al. Vascular endothelial growth factor messenger RNA expression level is preserved in liver metastases compared with corresponding primary colorectal cancer. Clin Cancer Res. 2006;12:29–33.CrossRefPubMed
8.
go back to reference Ishihama H, Chida M, Araki O, Karube Y, Seki N, Tamura M, et al. Comparison of 5-fluorouracil-related gene expression levels between adenocarcinomas and squamous cell carcinomas of the lung. Jpn J Clin Oncol. 2009;39:33–6.CrossRefPubMed Ishihama H, Chida M, Araki O, Karube Y, Seki N, Tamura M, et al. Comparison of 5-fluorouracil-related gene expression levels between adenocarcinomas and squamous cell carcinomas of the lung. Jpn J Clin Oncol. 2009;39:33–6.CrossRefPubMed
9.
go back to reference Oyaizu T, Matsumura Y, Kobayashi S, Sado T, Ishihama H, Chida M. Tumor-related gene expression levels in pulmonary pleomorphic carcinoma. J Cardiothorac Surg. 2015;10:79.CrossRefPubMedPubMedCentral Oyaizu T, Matsumura Y, Kobayashi S, Sado T, Ishihama H, Chida M. Tumor-related gene expression levels in pulmonary pleomorphic carcinoma. J Cardiothorac Surg. 2015;10:79.CrossRefPubMedPubMedCentral
10.
go back to reference Salonga D, Danenberg KD, Johnson M, Metzger R, Groshen S, Tsao-Wei DD, et al. Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clinical Cancer Res. 2000;6:1322–7. Salonga D, Danenberg KD, Johnson M, Metzger R, Groshen S, Tsao-Wei DD, et al. Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clinical Cancer Res. 2000;6:1322–7.
11.
12.
go back to reference James SJ, Basnakian AG, Miller BJ. In vivo folate deficiency induces deoxynucleotide pool imbalance, apoptosis, and mutagenesis in Chinese hamster ovary cells. Cancer Res. 1994;54:5075–80.PubMed James SJ, Basnakian AG, Miller BJ. In vivo folate deficiency induces deoxynucleotide pool imbalance, apoptosis, and mutagenesis in Chinese hamster ovary cells. Cancer Res. 1994;54:5075–80.PubMed
13.
go back to reference Kawakami K, Rusziewicz A, Bennett G, Moore J, Watanabe G, Iacopetta B. The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase. Clin Cancer Res. 2003;9:5860–5.PubMed Kawakami K, Rusziewicz A, Bennett G, Moore J, Watanabe G, Iacopetta B. The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase. Clin Cancer Res. 2003;9:5860–5.PubMed
14.
go back to reference Odin E, Wettergren Y, Nilsson S, Willen R, Carlsson G, Spears CP, et al. Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients. Clin Cancer Res. 2003;9:6012–9.PubMed Odin E, Wettergren Y, Nilsson S, Willen R, Carlsson G, Spears CP, et al. Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients. Clin Cancer Res. 2003;9:6012–9.PubMed
15.
go back to reference Pescarmona E, Pisacane A, Pignatelli E, Baroni CD. Expression of epidermal and nerve growth factor receptors in human thymus and thymomas. Histopathology. 1993;23:39–44.CrossRefPubMed Pescarmona E, Pisacane A, Pignatelli E, Baroni CD. Expression of epidermal and nerve growth factor receptors in human thymus and thymomas. Histopathology. 1993;23:39–44.CrossRefPubMed
16.
go back to reference Suzuki E, Sasaki H, Kawano O, et al. Expression and mutation statuses of epidermal growth factor receptor in thymic epithelial tumors. Jpn J Clin Oncol. 2006;36:351–6.CrossRefPubMed Suzuki E, Sasaki H, Kawano O, et al. Expression and mutation statuses of epidermal growth factor receptor in thymic epithelial tumors. Jpn J Clin Oncol. 2006;36:351–6.CrossRefPubMed
17.
go back to reference Nakagiri T, Funaki S, Kadota Y, Takeuchi Y, Shiono H, Akashi A, et al. Does gefitinib have effects on EGFR mutation-positive thymoma? –Case report of thymoma recurrence. Ann Thorac Cardiovasc Surg. 2014;20(Suppl):674–6.CrossRefPubMed Nakagiri T, Funaki S, Kadota Y, Takeuchi Y, Shiono H, Akashi A, et al. Does gefitinib have effects on EGFR mutation-positive thymoma? –Case report of thymoma recurrence. Ann Thorac Cardiovasc Surg. 2014;20(Suppl):674–6.CrossRefPubMed
18.
go back to reference Bellmunt J, Paz-Ares L, Cuello M, et al. Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy. Ann Oncol. 2007;18:522–8.CrossRefPubMed Bellmunt J, Paz-Ares L, Cuello M, et al. Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy. Ann Oncol. 2007;18:522–8.CrossRefPubMed
19.
go back to reference Lord RV, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clinical Cancer Res. 2002;8:2286–91. Lord RV, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clinical Cancer Res. 2002;8:2286–91.
20.
go back to reference Ikeguchi M, Arai Y, Maeta Y, Ashida K, Katano K, Wakatsuki T. Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer. Surg Today. 2011;41:1196–9.CrossRefPubMed Ikeguchi M, Arai Y, Maeta Y, Ashida K, Katano K, Wakatsuki T. Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer. Surg Today. 2011;41:1196–9.CrossRefPubMed
Metadata
Title
Tumor-related gene expression levels in thymic carcinoma and Type B3 thymoma
Authors
Yoko Karube
Satoru Kobayashi
Sumiko Maeda
Tetsu Sado
Hiromi Ishihama
Masayuki Chida
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Cardiothoracic Surgery / Issue 1/2016
Electronic ISSN: 1749-8090
DOI
https://doi.org/10.1186/s13019-016-0468-1

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