Prostate Specific Antigen (Human Kallikrein Protein 3) Expression in Maxillofacial Cysts and Tumors
Non-inflammatory odontogenic cysts and tumours vary in clinical appearance and growth potential, and can cause widespread destruction and deformation of the maxillofacial complex. It has been suggested that proteases may play a role in the differing pathogenesis of these cysts and tumours. Avenues for early identification and or minimally invasive therapeutic intervention are lacking.
Human kallikrein proteins (KLKs) are a group of 15 serine proteases implicated in a wide variety of signalling and regulatory roles. Some KLKs have been shown to be tumour suppressors in breast and gastric cancer, while over-expression of many KLKs is also associated with cancer/neogenesis. KLKs have been implicated in the transition of epithelial cells, ultimately leading to metastasis. KLK 3, better known as prostate specific antigen (PSA) is involved in seminal clot liquefaction, assisting in sperm motility after ejaculation through hydrolysis of seminal vesicle proteins. KLK 3 has a number of other substrates including laminin, TGF-Beta and other peptide hormones. KLK 3 is elevated in prostatic pathologies including prostate cancer, and benign prostate hypertrophy. Measurement of serum PSA/KLK 3 is useful to aid in detection of early prostate cancer, as well as to assess progression of disease.
This study aims to evaluate common neoplasms & cysts of odontogenic origin including the lateral periodontal cyst, dentigerous cyst, keratocystic odontogenic tumour (KOT) and ameloblastoma for the presence of KLK 3. Subsequently, we wish to investigate the role of KLK 3 in the pathogenesis and progression of these neoplasms.
Materials and Methods
Archived paraffin embedded samples from the division of oral pathology at the Western University of Canada were obtained, cut and assessed for the presence of KLK 3 using a standard immunostaining technique, utilizing a polyclonal antibody for KLK 3. Sixty (n=60) lesions were investigated including lateral periodontal cysts (n=9), dentigerous cysts (n=10), keratocystic odontogenic tumours (n=11) and ameloblastomas (n=11) as well as nasopalatine duct cysts (n=9, non-odontogenic cystic control) and odontomas (n=10, neoplasm control). Analysis of immunostaining was performed utilizing a scoring system assessing staining intensity as well as proportion of cells stained. These scores were combined to yield a total score for each sample examined. Epithelial staining, was examined and scored. Data was analyzed using the Kruskal-Wallis, as well as Dunn’s multiple comparison test.
Results
Kruskal-Wallis analysis shows a significant difference in staining intensity of KLK 3 between the groups of lesions evaluated (p=0.004). There is a significant difference in expression of KLK 3 when comparing the odontoma to KOT (p<0.05) and odontoma to ameloblastoma (p<0.01). Positive staining for KLK 3 was also observed in the lateral periodontal cyst, dentigerous cyst and nasopalatine duct cyst, however no significant differences were noted when comparing these other types of lesions.
Conclusion
For the first time, KLK 3 has been identified in odontogenic tissues. KLK 3 is present in significantly greater amounts in benign neoplasms of odontogenic origin, the ameloblastoma and KOT, when compared to the odontogenic hamartoma. KLK 3 is expressed in odontogenic neoplasms including the lateral periodontal cyst, dentigerous cyst, and odontomas. Positive identification of this biomarker may prove to be a diagnostic avenue for early detection and treatment of these locally destructive diseases.
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