title: Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma.
abstract: Cell cycle regulators, such as cyclinD1 and p53, play major roles in the tumor response to radiation and chemotherapy in esophageal squamous cell carcinoma (SCC). Pin1-mediated prolyl-isomerization potentiates cell cycle progression and cell proliferation, including the regulation of cyclinD1 and p53. Herein, we investigated the effect of Pin1 in association with cyclinD1 and p53 on the sensitivity of esophageal SCC to chemoradiotherapy (CRT). The expression levels of Pin1, cyclinD1 and p53 were examined immunohistochemically in endoscopic biopsy specimens from 68 advanced esophageal SCC patients before CRT to determine whether their expression levels predicted the clinical effectiveness of CRT in individual cancers. Forty-six of the 68 patients (67.6%) had an effective response to CRT, whereas 22 patients (32.4%) had an ineffective response. There was no significant correlation between clinical responses and expression levels of cyclinD1 or p53. However, the clinical response of the high Pin1 expression group was significantly higher than that of the low expression group (P=0.0200). Moreover, our data indicate that the combined immunohistochemical evaluation of Pin1, cyclinD1 and p53 expression in pretreatment biopsy samples is a useful indicator of sensitivity to CRT in advanced esophageal SCC. Thus, Pin1 may influence cyclinD1 and p53 functions and predict CRT sensitivity.
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan. mfukuchi@med.gunma-u.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fukai
authors.forename: Makoto
authors.initials: M
authors.lastname: Sohda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakajima
authors.forename: Takanori
authors.initials: T
authors.lastname: Inose
authors.forename: Naritaka
authors.initials: N
authors.lastname: Tanaka
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tsukada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000032:analysis; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: C530104:CCND1 protein, human; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase