Purpose: To identify predictive biomarkers of recurrence in NFPTs, we used heat shock protein profiling approach to correlate protein expression profiles with tumor recurrence. Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. The expression of HSPs in tumors has been implicated in the regulation of apoptosis. In the current study, we attempted to clarify the significance of HSPs in NFPTs and their correlation with clinicopathological parameters.
Experimental design: Expression levels of the HSP27, HSP27pS15, HSP27pS82, HSP47, HSP60, and HSP70, were studied using immunohistochemistry on 200 NFPTs. Normal pituitaries from 10 healthy patients were used as controls in the study. Among 200 h NFPTs, 44 patients have a recurrence after undergoing primary resection. HSP expression was evaluated according to the percentage of positively stained cells, and the intensity of staining. Data are presented as the mean ±standard deviation of the mean (S.D.). P-value <0.05 was considered as significant.
Results: Patients were in the age group of 2865 years, with a mean age of 43.1 (±12.6) years. Immunohistochemistry with SF-1 and FSH/LH-α classified 45.5% NFPT as gonadotropinoma 3% silent somatropinoma (pit-1 positive), and 7.5% silent corticotropinoma (T-pit positive). Among these 200 patients, 44 recurrence events were observed after a total of 15 years of follow-up (median=4 years). Among all the HSPs, HSP47, HSP60, and HSP70 were under-expressed while HSP27pS82 was augmented (P<0.001) in recurrent tumors. HSP27pS82 was also overexpressed in invasive NFPTs (P = 0.01). There was no change in HSP27 and HSP27pS15 expression levels. ROC curve indicated HSP27pS82 as a good marker for discriminating recurrent tumors from non-recurrent tumors (AUC = 0.738).
Conclusions: Thus, we conclude that HSP27pS82 could be a good prognostic marker for recurrent NFPTs. Additionally, HSP27pS82 can also serve as a therapeutic target.