Expression And Clinical Significance Of Melatonin Receptor (MT₁) In Osteosarcoma

Background Osteosarcoma is the most common malignant bone tumor that threats the life of the juveniles, it has high rate of lung metastases and progresses rapidly,80% of patients have micrometastases at diagnosis.In recent years, the survival rate has been improved significantly with the application of neoadjuvant chemotherapy, surgical advances, but the treatment has begun to enter the plateau.More and more scholars began to focus on biological regulation therapy, immune and gene therapy in the hope that finding new ways to the treatment of osteosarcoma.Experiments confirmed that melatonin can inhibit the growth of breast cancer, prostate cancer and some other tumors.There has been hypothesized that melatonin can improve the quality of life and clinical prognosis of patients. Melatonin plays antitumor effect mainly through binding to its receptor MT1.To our knowledge,there has rarely report on the expression of MT1 in osteosarcoma.Objective To detect the expression of melatonin receptors (MT1) in osteosarcoma, and its clinical significance, to provide a theoretical basis for the use of melatonin in the treatment of osteosarcoma.Materials and Methods Paraffin tissue blocks of 40 cases of osteosarcoma and 20 cases of osteochondroma with a complete clinical data and pathological data were collected between June 2003 and June 2009 of Qilu Hospital. All 60 specimens were stained by immunohistochemical method. Then we analyzed associations between the receptor expression and known prognostic clinicopathologic parameters such as age, sex, tumor size, Enneking stage, Dahlin's histological type, recurrence and metastasis.Results The majority of osteochondroma samples (13/20 [75%]) were negative, while moderate to strong reactivity was seen in most osteosarcoma samples (28/40 [70%]). Thus, although MT1 receptors were detectable in osteochondroma, high receptor level occurred more frequently in osteosarcoma samples (P<0.05), and tumors with moderate or strong reactivity were more likely to be with high Enneking stage and with recurrence or metastasis(P<0.05). No significant association was found for gender, age, tumor size, Dahlin's histological type(P>0.05).Conclusion we report the first use of immunohistochemical analysis to determine the distribution of the high affinity melatonin receptor subtype, MT1, in osteosarcoma.We found that MT1 is abundantly expressed in osteosarcoma specimens.And tumors with moderate or strong reactivity were more likely to be with high Enneking stage and with recurrence or metastasis. High expression of MT1 provides a wealth of binding sites for melatonin. These findings may have implications for the use of melatonin in osteosarcoma therapy.