Expression of heat shock protein 70 in nasopharyngeal carcinomas: different expression patterns correlate with distinct clinical prognosis

Abstract

Background: Heat shock protein 70, a stress protein, has been implicated in tumor progression. However, its role in nasopharyngeal carcinoma (NPC) progression has not yet been clearly investigated.

Methods: Immunohistochemistry (IHC) was employed to examine the expression patterns of Hsp70, human leukocyte antigen -A (HLA-A) in NPC tissue samples.

Results: The expression of Hsp70 exhibited different spatial patterns among nuclear, membrane and cytoplasm in 507 NPC tumor tissues. Kaplan-Meier survival analysis demonstrated that different Hsp70 expression patterns are correlated with different patient outcomes. High membranal and cytoplasmic levels of Hsp70 predicted good survival of patients. In contrast, high nuclear abundance of Hsp70 correlated with poor survival. Moreover, the membranal and cytoplasmic levels of Hsp70 were positively correlated with levels of the MHC I molecule HLA-A.

Conclusions: Different Hsp70 expression patterns had distinct predictive values. The different spatial abundance of Hsp70 may imply its important role in NPC development and provide insight for the development of novel therapeutic strategies involving immunotherapy for NPC.

Figure 1

Different expression patterns of Hsp70 in NPC tumor tissues.A, Low and high expression levels of Hsp70 in the membrane and cytoplasm in the TMA are shown under both low and high magnification. B, Low and high levels of Hsp70 nuclear abundance in the TMA are shown under both low and high magnification. Scale bars, 100 μm.

Figure 2

Selection of the cutoff scores. Receiver operating characteristic curve analysis was employed to determine the cutoff score for the designation of “high expression” of Hsp70 with membranal, cytoplasmic or nuclear staining. The sensitivity and specificity for each outcome of Hsp70 membranal and cytoplasmic staining were plotted: ( A) T classification ( P =0.002); ( B) N classification ( P =0.029); ( C) Clinical stage ( P =0.029); ( D) Cancer progression ( P <0.001); ( E) Survival status ( P <0.001). The sensitivity and specificity for each outcome of Hsp70 nuclear staining were plotted: ( F) T classification ( P =0.964); ( G) N classification ( P =0.97); ( H) Clinical stage ( P =0.99); (I) Cancer progression ( P =0.009); (J) Survival status ( P =0.005).

Figure 3

The association of different Hsp70 expression patterns with NPC patient survival. TMA analyses of a cohort of 507 NPC patients diagnosed at M0 were conducted. A and B, high Hsp70 membranal and cytoplasmic expression levels were significantly positively associated with overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.001) in all NPC patients. C and D, high Hsp70 nuclear abundance were significantly negatively associated with overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.005) in NPC patients.

Figure 4

Correlation between expression levels of Hsp70 and the level of HLA-A in NPC tissues.A, continuous sections of human NPC tissue were subjected to IHC staining with antibodies against Hsp70 and HLA-A. The high membranal and cytoplasmic expression levels of Hsp70 in the tumor tissue in case 1 were accompanied by an elevated level of HLA-A. Conversely, the low membranal and cytoplasmic expression levels of Hsp70 in the tumor tissue of case 2 were accompanied by a low level of HLA-A. Scale bars = 100 μm. B, in 226 NPC cases with high membranal and cytoplasmic expression levels of Hsp70, an average HLA-A score was 3.82 ( right column), an average score that was significantly higher than that (2.81) of the 281 NPCs with low expression levels of Hsp70 ( left column, P < 0.001, independent sample t-test).