Comparison of the expression of 5 heat shock proteins in benign and malignant salivary gland tumor tissues

Abstract

The objective of this study was to analyze the significance and potential value of heat shock proteins (HSPs) in salivary gland tumors. We found that expression of HSP60, HSP70, HSP86 and HSP84 were all upregulated in both salivary gland benign tumors and malignant tumors, and that the expression of HSP70, HSP86 and HSP84 was more greatly overexpressed in the malignant tumors (each P<0.01). For HSP27, expression was upregulated both in malignant and benign tumors, with less expression observed in malignant tumors (P<0.01). In malignant tumors, expression of HSP27 was negatively correlated with the age of the patients, size of the tumor tissue, occurrence of neural invasion and metastasis (each P<0.05). Additionally, in malignant tumors, HSP70 and HSP86 were both positively correlated with occurrence site, neural invasion and metastasis (each P<0.05), while HSP60 was only negatively correlated with the age of the patients (P<0.05). HSP86 was also positively correlated with malignant degree (P<0.01). In malignant tumors, the proliferation index (PI), which was marked by proliferating cell nuclear antigen (PCNA; PCNA-PI) was 49.95±14.569, which was significantly higher compared with that in benign tumors (P<0.001), which was in accordance with the upregulation of HSP70, HSP86 or HSP84; however, an adverse correlation was found between HSP27 expression and PCNA (each P<0.05). In conclusion, these results suggest that HSPs are involved in the occurrence and development of salivary gland tumors. HSP70, HSP86 and HSP84 retained the higher multiplication capability of the malignant tumor cells, however, HSP27 did not. Thus, the upregulation of HSP70, HSP86 and HSP84 and the downregulation of HSP27 may all be used as biomarkers of the occurrence and development of malignant salivary gland tumors. Moreover, the extremely high expression of HSP86 and HSP84 in benign tumors indicates the malignant transformation potential.

Keywords: heat shock proteins; proliferating cell nuclear antigen; salivary gland tumor; significance.

Figure 1

Expression location and strength of 5 HSPs in salivary gland tumors. (A) Expression location and strength of 5 HSPs (IHC-SP staining; magnification, ×400). HSP27 and HSP60 were located in the cytoplasm of the tumor epithelium, but in adenolymphoma they were mainly expressed in (a1) the lower epithelium and (b1) the top epithelium, respectively. HSP70 was significantly expressed in the nucleus and cytoplasm, but (d) HSP86 and (e) HSP84 were mainly located in the cytoplasm and partly expressed in nucleus. Expression of HSP27 was less in (a2) malignant tumor compared with (a1) benign tumor, but (c2) HSP70, (d2) HSP86 and (e2) HSP84 were all stronger in malignant tumor compared with (c1, d1 and e1) benign tumor. (B) Histograms of expression strength of the 5 HSPs. ^*P<0.05; ^**P<0.01; malignant tumor (group) vs. benign tumor (group). ^***P<0.001. HSPs, heat shock proteins.

Figure 2

Expression comparison of 5 HSPs in benign types of salivary gland tumor (n=41). (A) Micrograph of expression strength of HSPs. (IHC-SP staining; magnification, ×400). Expression of (a) HSP86 and (b) HSP84 was greater in the mixed tumors, but less in the adenolymphoma and other benign tumor groups. (B) Histogram of expression strength of 5 HSPs. ^*P<0.05; ^***P<0.001. M, mixed tumor; A, adenolymphoma; O, other benign tumors; HSP, heat shock proteins.

Figure 3

Expression of PCNA and co-expression with HSPs in salivary gland malinant tumors. (A) In adenoid cystic carcinoma, higher PCNA-PI was located in the nucleus of tumor cells. (IHC-SP staining; magnification, ×400). (B) PCNA (AP-Red staining indicated by bright red color) and HSP86 (DAB staining indicated by brownish yellow color) co-located in the nuclei of tumor cells (IHC-Dou SP staining; magnification, ×400). (C) PCNA (AP-Red staining indicated by bright red color) and HSP27 (DAB staining indicated by brownish-yellow color) were respectively located in the nuclei and plasma of same or different tumor cells, with reverse expression trend (IHC-Dou SP staining; magnification, ×400). PCNA, proliferating cell nuclear antigen; HSP, heat shock protein; PCNA-PI, proliferating cell nuclear antigen-proliferating index.

Figure 4

Correlation between the expression of 5 HSPs and PCNA-PI in salivary gland malinant tumors. In salivary gland malinant tumors, the PCNA-PI was positively correlated with expression of HSP70, HSP86 and HSP84 (each P<0.05), but was negatively correlated with HSP27. ^*Comparison between the group of +/++ or +++ and the − group. ^▴Comparison between the +/++ group and the +++ group. HSPs, heat shock proteins; PCNA-PI, proliferating cell nuclear antigen-proliferating index.