Expression of the prolyl isomerase Pin1 is a useful indicator of sensitivity to chemoradiotherapy in advanced esophageal squamous cell carcinoma

Abstract

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. Fortysix 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.

Pin1 positively affects tumorigenesis of esophageal squamous cell carcinoma and correlates with poor survival of patients

“…Pin1 was expressed moderately or strongly in 56% ESCC tumors. The percentage of high Pin1 expression in our patients was higher than that of earlier reports, in which 31–37% of ESCC samples exhibited high Pin1 expression [ 9 – 11 ]. This difference might result from different IHC scoring criteria.…”

“…The association between Pin1 expression and clinicopathlogical factors in ESCC was previously reported [ 9 – 11 ]. In this study, we examined Pin1 expression in ESCC specimens.…”

“…Pin1 overexpression was previously reported to be correlated with lymph node metastasis and poor overall survival in ESCC patients treated with surgery [ 9 , 10 ]. In patients treated with definitive chemoradiotherapy, the clinical response in high Pin1 expression group was higher than that of the low expression group [ 11 ]. However, the role of Pin1 has not been experimentally examined in ESCC cell lines.…”

High stathmin 1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma

“…Concurrent chemotherapy consisted of 7 mg/m 2 docetaxel intravenously administered for 1 h before radiotherapy on days 1, 8, 15 and 22. Treatment, toxicity, and response evaluation details were previously described (26).…”