Evaluation of Midkine Expression in Dentigerous Cysts, Odontogenic Keratocysts and Different Types of Ameloblastoma.

OBJECTIVE Midkine is a heparin-binding growth factor whose expression is increased in most tumors, namely ameloblastomas. This study aimed to compare Midkine expression in different odontogenic lesions. MATERIAL AND METHOD This analytical cross-sectional study was performed on 52 definitely diagnosed odontogenic lesions including 15 dentigerous cysts, 13 odontogenic keratocysts, and 17 unicystic and 5 multicystic ameloblastomas archived from 1997 to 2015. Midkine expression was examined in tissue samples through immunohistochemistry. The nonparametric Kruskal-Wallis and Mann-Whitney tests were run as appropriate (P < 0.05). RESULTS The frequency of Midkine expression was < 20% in 7.7%, 20-50% in 25%, and > 50 % in 67.3% of the samples, indicating significant differences among the groups (P = 0.002). Moreover, the expression intensity was strong in 63.5%, moderate in 23.1%, and weak in 13.5% of odontogenic lesion samples (P = 0.071). The total staining score was weak in 3.8%, moderate in 48.1%, and strong in 48.1% of the cells, displaying significant differences between the study groups in this regard (P = 0.043). CONCLUSION Midkine can be considered as both a differentiating factor and a molecular-targeted therapy in odontogenic lesions. Yet, further studies are required to approve the role of this cytokine in different biological and pathological stages of the tumors.

[1]  R. Seethala,et al.  Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland , 2017, Head and Neck Pathology.

[2]  D. Ye,et al.  Elevated plasma midkine and pleiotrophin levels in patients with systemic lupus erythematosus , 2016, Oncotarget.

[3]  Jun Chen,et al.  [Expression of midkine and microvessel density in salivary adenoid cystic carcinoma]. , 2016, Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology.

[4]  A. Vajgel,et al.  Recurrence rate following treatment for primary multicystic ameloblastoma: systematic review and meta-analysis. , 2016, International journal of oral and maxillofacial surgery.

[5]  Y. Choi,et al.  Strong immunoexpression of midkine is associated with multiple lymph node metastases in BRAFV600E papillary thyroid carcinoma. , 2015, Human pathology.

[6]  Jun Zhang,et al.  The clinical and prognostic significance of midkine in breast cancer patients , 2015, Tumor Biology.

[7]  W. Tilakaratne,et al.  Diagnostic dilemma of unicystic ameloblastoma: novel parameters to differentiate unicystic ameloblastoma from common odontogenic cysts. , 2014, Journal of investigative and clinical dentistry.

[8]  M. Gallottini,et al.  Peripheral ameloblastoma with dystrophic calcification: an unusual feature in non-calcifying odontogenic tumors. , 2014, Brazilian dental journal.

[9]  John M. Wright,et al.  A review of research on salivary biomarkers for oral cancer detection , 2014, Clinical and Translational Medicine.

[10]  E. Gramage,et al.  The expression and function of midkine in the vertebrate retina , 2014, British journal of pharmacology.

[11]  Qiang Wang,et al.  Midkine expression is associated with clinicopathological features and BRAF mutation in papillary thyroid cancer , 2014, Endocrine.

[12]  K. Rau,et al.  Midkine neurite growth-promoting factor 2 expression as a potential prognostic marker of adjuvant therapy in head and neck squamous cell carcinoma , 2013, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[13]  T. P. Almeida,et al.  Expression of midkine in ameloblastomas and its correlation with clinicopathologic parameters. , 2012, Oral surgery, oral medicine, oral pathology and oral radiology.

[14]  T. Silva,et al.  Midkine expression in oral squamous cell carcinoma and leukoplakia. , 2012, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[15]  K. Komiyama,et al.  Midkine expression in human periapical granulomas. , 2011, Journal of endodontics.

[16]  T. Miyashita,et al.  Multiple keratocystic odontogenic tumors associated with nevoid basal cell carcinoma syndrome having distinct PTCH1 mutations: a case report. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[17]  L. Gaitán-Cepeda,et al.  Reclassification of odontogenic keratocyst as tumour. Impact on the odontogenic tumours prevalence. , 2010, Oral diseases.

[18]  J. Martínez-González,et al.  Metaanalysis of the epidemiology and clinical manifestations of odontomas. , 2008, Medicina oral, patologia oral y cirugia bucal.

[19]  A. Lazar,et al.  Midkine Enhances Soft-Tissue Sarcoma Growth: A Possible Novel Therapeutic Target , 2008, Clinical Cancer Research.

[20]  M. Fujiwara,et al.  Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors. , 2008, Human pathology.

[21]  T. Ji,et al.  Evaluation of expression of midkine in oral squamous cell carcinoma and its correlation with tumour angiogenesis. , 2007, International journal of oral and maxillofacial surgery.

[22]  H. Mehdorn,et al.  Overexpression of midkine contributes to anti‐apoptotic effects in human meningiomas , 2007, Journal of neurochemistry.

[23]  N. Nakamura,et al.  Midkine induced growth of ameloblastoma through MAPK and Akt pathways. , 2004, Oral oncology.

[24]  T. Muramatsu,et al.  Midkine and pleiotrophin in neural development and cancer. , 2004, Cancer letters.

[25]  L. Haynes,et al.  The pleiotropin/midkine family of cytokines: role in glial-neuronal signalling. , 2001, Progress in brain research.