Hsp60 in embryonic and adult submandibular salivary gland: quantitative distribution patterns in normal tissue and comparison with benign and malignant tumors

Abstract

Introduction: Heat Shock Protein 60 (Hsp60) is a member of the chaperoning system that assists protein folding inside mitochondria and plays other roles beyond these organelles. It is implicated in the carcinogenic processes in various types of cancer. In human salivary glands, Hsp60 has not yet been measured or mapped in detail and its role in gland development and functioning is virtually unknown. Consequently, its potential as biomarker for gland diseases, including malignancies cannot be assessed. The S-100 protein, a known marker for schwannomas, has been found also in myoepithelial-cell carcinomas of the salivary glands. Here, we present our initial findings on the anatomic-histological distribution of Hsp60 in human submandibular salivary gland (SMG) at various stages of development and its changes during tumorigenesis, in parallel with changes of S-100 in salivary gland tumors. Methods: Adult human submandibular gland (normal and tumoral) and embryonic head tissue samples were processed by standard methods for routine histological analysis. Additionally, these same sections underwent immunohistochemical staining using antibodies against Hsp60 and S- 100. Specimens from patients were obtained from the archives of the Human Pathology Section, Department of Health Science, University of Palermo, Italy. All procedures were in accordance with the Helsinki Declaration. We determined the percentages of cells immunopositive for Hsp60 or S-100 and made comparative evaluations applying the one way ANOVA. Results: Hsp60 was present in the acini and ducts of embryonic salivary glands but had a different distribution pattern in adult glands: it occurred only in the ducts and in a few acini. In contrast, Hsp60 was not detected in Pleomorphic Adenoma (PA) or Warthin’s tumor (WT) , whereas its levels were high in Adenoid Cystic Adenoma (ACC) . S-100 was present in the nuclei and/or in the cytoplasm in PA and ACC and its levels in the nuclei in ACC were higher than in the PA nuclei . Conclusions: Since the chaperonin is abundant in acini and ducts of embryonic salivary glands, it can be hypothesized that it actively participates in the developmental process leading to the formation of a wholly functional adult, mature organ. Hsp60 and S-100 immunopositivities were high in the malignant tumor implying their involvement in neoplasm formation and progression. These results foreshadow the diagnostic and prognostic potential of Hsp60 and S-100 when measured side by side as biomarkers useful for distinguishing between benign and malignant tumors.