Expression of receptor tyrosine kinases in esophageal carcinosarcoma

Sano,Akihiko; Sakurai,Shinji; Kato,Hiroyuki; Suzuki,Shigemasa; Yokobori,Takehiko; Sakai,Makoto; Tanaka,Naritaka; Inose,Takanori; Sohda,Makoto; Nakajima,Masanobu; Fukai,Yasuyuki; Miyazaki,Tatsuya; Ojima,Hitoshi; Hosoya,Yoshinori; Enomoto,Takehiko; Kanda,Tatsuo; Ajioka,Yoichi; Kuwano,Hiroyuki

doi:10.3892/or.2013.2371

Expression of receptor tyrosine kinases in esophageal carcinosarcoma

Authors:
- Akihiko Sano
- Shinji Sakurai
- Hiroyuki Kato
- Shigemasa Suzuki
- Takehiko Yokobori
- Makoto Sakai
- Naritaka Tanaka
- Takanori Inose
- Makoto Sohda
- Masanobu Nakajima
- Yasuyuki Fukai
- Tatsuya Miyazaki
- Hitoshi Ojima
- Yoshinori Hosoya
- Takehiko Enomoto
- Tatsuo Kanda
- Yoichi Ajioka
- Hiroyuki Kuwano
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Affiliations: Department of Gastroenterological Surgery, Gunma Prefectural Cancer Center, Ohta, Gunma 373-8550, Japan, Department of Diagnostic Pathology, Gunma Central General Hospital, Maebashi, Gunma 371-0025, Japan, Department of Surgical Oncology, Dokkyo Medical University, Mibu, Shimotsuga, Tochigi 321-0293, Japan, Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan, Department of Surgery, Jichi Medical University, Tochigi 329-0498, Japan, Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata 951-8510, Japan, Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata 951-8510, Japan
Published online on: March 29, 2013 https://doi.org/10.3892/or.2013.2371
Pages: 2119-2126

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Abstract

Esophageal carcinosarcoma (ECS) is a rare malignant neoplasm associated with a poor patient prognosis. It is characterized by the presence of both malignant epithelial and mesenchymal components. Molecular-targeted therapy of several receptor tyrosine kinases (RTKs) has been reported to be effective in the treatment of various malignant tumors, including carcinosarcoma of several organs. This study aimed to assess the therapeutic potential of targeting RTKs in ECS. Overexpression of RTKs was assessed in 21 ECS cases by immunohistochemistry (IHC). Positively stained cases were further examined for RTK gene mutations and amplifications by direct sequencing analysis and fluorescence in situ hybridization. In epithelial components, KIT, platelet-derived growth factor receptor (PDGFR)A, PDGFRB, MET, epidermal growth factor receptor (EGFR) and HER-2 were overexpressed in 1 (4.8%), 1 (4.8%), 0 (0%), 11 (52.4%), 13 (61.9%) and 2 (9.5%) cases, respectively. In the mesenchymal components the corresponding numbers of cases were 2 (9.5%), 2 (9.5%), 0 (0%), 12 (57.1%), 11 (52.4%) and 0 (0%). No mutations in the c-kit, PDGFRA and c-met genes were found. Among 19 EGFR-positive tumors, 2 had EGFR missense mutations (T790A, exon 20) only in the mesenchymal component. Gene amplification or high polysomy of c-kit, PDGFRA, c-met and EGFR was observed in 1 (33.3%), 0 (0%), 3 (18.8%) and 10 (52.6%) cases, respectively. In conclusion, various RTKs, particularly MET and EGFR were overexpressed in ECSs suggesting that molecular-targeted therapies directed to MET, EGFR or other RTKs may be effective in inhibiting the growth or progression of the epithelial and/or mesenchymal component of ECS.

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