title: Expression of receptor tyrosine kinases in esophageal carcinosarcoma.
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.
authors.affiliation: Department of Gastroenterological Surgery, Gunma Prefectural Cancer Center, Ohta, Gunma 373-8550, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sano
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakurai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Suzuki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.forename: Makoto
authors.initials: M
authors.lastname: Sakai
authors.forename: Naritaka
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takanori
authors.initials: T
authors.lastname: Inose
authors.forename: Makoto
authors.initials: M
authors.lastname: Sohda
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakajima
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fukai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ojima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hosoya
authors.forename: Takehiko
authors.initials: T
authors.lastname: Enomoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002296:Carcinosarcoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met