Significance of unphosphorylated and phosphorylated heat shock protein 27 as a prognostic biomarker in pancreatic ductal adenocarcinoma
Richard Drexler, Kim C. Wagner, Mirco Küchler, Bernd Feyerabend, Moritz Kleine, Karl J. Oldhafer
Abstract
PURPOSE: Few studies reported about the potential of unphosphorylated heat shock protein 27 (HSP27) and phosphorylated heat shock protein 27 (pHSP27) as a predictor for survival and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). In this study, we analysed the expression patterns of pHSP27 and HSP27 in a patient population after surgery and correlated the immunohistochemical results with clinicopathological data and long-term outcome of the patients. METHODS: HSP27 and pHSP27 (Ser-15, Ser-78 and Ser-82) protein expression were analysed by immunohistochemistry using the immunoreactive score (IRS) from paraffin-embedded tissue of 106 patients with PDAC who underwent surgery. Immunohistochemical results were correlated with clinicopathological data, disease-free (DFS) and overall survival (OS). RESULTS: HSP27 expression was significantly lower in patients with a shorter OS (p = 0.006) and DFS (p < 0.0001). A higher HSP27 expression was associated with a better response to gemcitabine in the resected, non-metastasised patients group (p = 0.001). Furthermore, HSP27 was downregulated in patients suffering from metastases at time of surgery (p < 0.001) and in undifferentiated tumours (p = 0.007). In contrast, pHSP27-Ser15, -Ser78 and -Ser82 were not associated with any survival data of the study population. CONCLUSION: HSP27 seems to be a strong indicator for the prediction of OS and DFS. Moreover, HSP27 could play a role in the formation and migration of liver metastases of PDAC.