Selected Human Kallikrein (KLK) Expression in Odontogenic Cysts and Tumors
KLKs are a group of 15 serine proteases, the best known of which is KLK3 (prostate specific antigen), widely used in the screening and monitoring of prostate carcinoma. KLK6 is increased in salivary gland and ovarian tumors, and is involved in tumor invasion, E-cadherin shedding, promotion of cell proliferation, migration and invasion, and skin desquamation. KLK7 has a role in salivary gland, ovarian, breast, lung, cervical, and endometrial cancers, and is involved in tumor invasion and skin desquamation. KLK8 is a tumor suppressor gene in breast cancer, along with KLKs 6 and 10. KLK10 is decreased in prostate cancer, and is implicated in ovarian cancer and tumor cell invasion. KLK13 is involved in salivary gland, ovarian, and breast cancers, and tumor cell invasion. KLK14 plays a role in salivary gland and breast cancers.
Archived paraffin embedded samples obtained from the Division of Oral Pathology at the University of Western Ontario were assessed for the presence of KLKs 6,7,8,10,13, and 14 using a standard immunostaining technique, utilizing a polyclonal antibody for each. Sixty-one lesions were investigated including lateral periodontal cysts (n=10), dentigerous cysts (n=10), keratocystic odontogenic tumors (KOT) (n=11), ameloblastomas (n=10), nasopalatine duct cysts (n=10, non-odontogenic cystic control), and odontomas (n=10, neoplasm control). A scoring system assessing intensity and proportion of epithelial cells stained was used. These scores were combined to yield a total score for each sample. Data were analyzed using the Kruskal-Wallis and Dunn’s multiple comparison tests.
The expression of KLKs 6,7,8,10, and 13 differed among controls, cysts and tumors, while only KLK14 was expressed uniformly. KLK6 was statistically significantly higher in ameloblastomas than in dentigerous cysts, KOTs, and odontomas (p<0.001, p<0.001 and p<0.05 respectively). For KLK7, only KOTs and nasopalatine duct cysts (p<0.05) were significantly different. KLK8 was significantly higher in ameloblastomas than in KOTs (p<0.05). KLK10 expression was significantly higher in ameloblastomas than in nasopalatine duct cysts and odontomas (both p<0.05). KLK13 was statistically significantly greater in ameloblastomas than in lateral periodontal cysts (p<0.001), dentigerous cysts (p<0.001), and odontomas (p<0.001). KLK13 was also significantly higher in KOTs than in lateral periodontal cysts (p<0.05), dentigerous cysts (p<0.05), and odontomas (p<0.05). KLK14 did not exhibit preferential expression for these lesions.
The results suggest that KLKs 6, 7, 8, 10, and 13 are involved in the progression of aggressive odontogenic tumors (viz. ameloblastoma). KLK10 may have a greater role in odontogenic, rather than non-odontogenic, lesions. Also, the higher expression of KLK13 in KOTs and ameloblastomas suggests that it is important in the development of odontogenic tumors compared with cysts, and similarly, more important in odontogenic tumors and cysts compared with hamartomas and non-odontogenic cysts.
Overall, for the first time, it has been shown that KLKs 6,7,8,10,13, and 14 are present in the epithelium of odontogenic cysts and tumors. With future research, we hope to further define the specific roles of these KLKs in these cysts and tumors, and to determine if they can serve as biomarkers in early diagnosis and treatment monitoring.
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Borgono CA, Diamandis EP: The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer. 4:867, 2004