title: DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma.
abstract: This is the first report to correlate DARPP-32 immunoreactivity (dopamine and cAMP-regulated phosphoprotein, M(r) 32 000) to clinicopathological status in human cancer. DARPP-32 is recognised as a neuronal protein. A recent study demonstrated that DARPP-32, and a truncated isoform t-DARPP, are overexpressed in gastric carcinoma during the process of carcinogenesis. The biological function of DARPP-32, however, is still unclear. The purpose of this study was to clarify the roles of DARPP-32 and t-DARPP in oesophageal squamous cell carcinoma (OSCC). Initially, we investigated DARPP-32 and t-DARPP expression in OSCC cell lines by Reverse transcription-polymerase chain reaction and Western blot. DARPP-32 expression was observed in four out of seven (57.1%) cell lines, but t-DARPP expression was not observed in any cell lines. In oesophageal tissue sample, DARPP-32 expression was observed in four out of seven (57.1%) tumour tissues, while t-DARPP was not observed in any tissues. Subsequently, DARPP expression was assessed by immunohistochemistry, using a polyclonal antibody, in tissue sections from 122 patients with primary OSCC. DARPP immunoreactivity was not observed in any normal oesophageal mucous membranes. On the other hand, positive DARPP immunostaining was detected in 37 patients (30.3%) and correlated inversely with pathologic stage (P=0.0284), pT (P=0.0438), pN (P=0.0303) and tumour size (P=0.012). The overall survival rate was worse in patients with DARPP-negative tumours than in patients with DARPP-positive tumours (P=0.0453). Interestingly, DARPP expression was observed in only one out of 45 cases of dysplasia. These observations suggest that DARPP-32 (rather than t-DARPP) expression arises after a phase of dysplasia in OSCC, and that tumours expressing DARPP-32 progress less rapidly than DARPP-32-negative tumours.
authors.affiliation: Surgical Oncology, Cancer Medicine, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, N15W7 Kita-ku, Sapporo, Hokkaido 060-8638, Japan. yuma-ebi@wc4.so-net.ne.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Ebihara
authors.forename: M
authors.initials: M
authors.lastname: Miyamoto
authors.forename: A
authors.initials: A
authors.lastname: Fukunaga
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Shichinohe
authors.forename: Y
authors.initials: Y
authors.lastname: Kawarada
authors.forename: T
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Y
authors.initials: Y
authors.lastname: Cho
authors.forename: S
authors.initials: S
authors.lastname: Murakami
authors.forename: H
authors.initials: H
authors.lastname: Uehara
authors.forename: H
authors.initials: H
authors.lastname: Kaneko
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: S
authors.initials: S
authors.lastname: Okushiba
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.forename: H
authors.initials: H
authors.lastname: Katoh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins / Q000096:biosynthesis*; D011230:Precancerous Conditions; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins