title: Expression of copper-transporting P-type adenosine triphosphatase in human esophageal carcinoma.
abstract: A major obstacle in the treatment of esophageal carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphatase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed. Our goal was to investigate if ATP7B is expressed in esophageal carcinoma and whether its expression correlates with reduced responsiveness to cisplatin treatment. We retrospectively examined the expression of ATP7B in primary esophageal carcinoma and its association with chemotherapeutic effect. Tissues were surgically removed from 17 esophageal carcinoma patients. Twelve of them received cisplatin-based chemotherapy before surgery. We performed immunohistochemical analysis of ATP7B using a monoclonal antibody against ATP7B in 17 esophageal carcinomas. A variable degree of cytoplasmic staining of tumor cells was observed in 76.5% (13/17 cases) of the analyzed carcinomas. ATP7B expression was not observed in adjacent non-neoplastic tissues. ATP7B positivity was not significant in gender, age, histopathological grading or TNM categories. Patients with ATP7B-positive tumors tended to have an inferior response to chemotherapy compared with the patients with ATP7B-negative tumors. These findings suggest that overexpression of ATP7B in esophageal carcinoma could be associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, ATP7B gene expression might be considered as a chemoresistance marker for cisplatin in the patients of esophageal carcinoma and provider of important information on the strategy against esophageal carcinoma.
authors.affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8570, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Higashimoto
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kanzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimakawa
authors.forename: Soichi
authors.initials: S
authors.lastname: Konno
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Naritaka
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Nitta
authors.forename: Shiro
authors.initials: S
authors.lastname: Mori
authors.forename: Shinobu
authors.initials: S
authors.lastname: Shirata
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Terada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takebayashi
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000201:enzymology*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000627:therapeutic use; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004938:Esophageal Neoplasms / Q000201:enzymology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002945:Cisplatin; D005472:Fluorouracil