title: Expression status of CD44 and CD133 as a prognostic marker in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy followed by radical esophagectomy.
abstract: Cancer stem cells (CSCs) have self-renewal and pluripotency capabilities and contribute to cancer progression and chemoresistance. It has been proposed that the treatment resistance and heterogeneity of CSCs are deeply involved in the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to identify the influence of the expression status of the CSC markers CD44 and CD133 on chemotherapeutic efficacy and prognosis in ESCC patients who underwent radical esophagectomy after neoadjuvant chemotherapy (NAC). Endoscopically biopsied specimens taken before NAC and surgically resected specimens after NAC were immunohistochemically assessed for CD44 and CD133 expression for 47 ESCC patients who underwent NAC followed by radical esophagectomy. The correlation between CD44 and CD133 expression status and clinicopathological findings and the prognosis of ESCC patients after NAC followed by esophagectomy were analyzed. The percentages of CD44-positive cells and CD133-positive cells in specimens were increased after NAC. CD44 and CD133 expression status before NAC did not correlate with the degree of tumor progression and had no impact on the chemotherapeutic effect. However, strong expression of CD44 or CD133 and a high proportion of CD133-expressing cells before NAC were significantly associated with poorer esophageal cancer-specific survival. Patients with strong expression of CD44 or CD133 and those with a high ratio of CD133-positive tumor cells showed significantly poor prognosis regardless of the effect of chemotherapy. Multivariate analysis showed that simultaneous strong expression of CD44 and CD133 before NAC, a high rate of CD133-positive tumor cells before NAC, and primary tumor remission assessed by preoperative endoscopy were significant independent prognostic factors for ESCC. Our data indicate that CD44 and CD133 expression status prior to treatment dictates the malignant potential of ESCC and may be a novel predictor of recurrence and prognosis of ESCC patients after treatment.
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Ohbatake
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirose
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tsukada
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakanuma
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Seisho
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kinoshita
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Makino
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inokuchi
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Nakagawara
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tajima
authors.initials: T
authors.lastname: Hidehiro
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamura
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Department of Gastroenterologic Surgery, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human