The Expression And Clinical Significance Of PD-1/PD-L1 In Extraskeletal Osteosarcoma

Background: Extraskeletal osteosarcoma(ESOS)is a malignant soft tissue sarcoma which is not attached to the bone.The limbs are the common site of ESOS.The treatment is mainly based on surgery,supplemented by radiotherapy and chemotherapy.Due to ESOS'S high rate of recurrence and metastasis,the prognosis is significantly lower than osteosarcoma(OS)and there was no new breakthrough in treatment.PD-1 and its ligand PD-L1 are highly expressed in malignant tumors and are expected to become new therapeutic targets.Objective: Detecting the clinical features of ESOS and the difference between ESOS and OS.Detecting the expression of PD-1 and PD-L1 in ESOS and OS specimens,and analyze the correlation between PD-1/PD-L1 and prognosis.Method: 8 patients with ESOS and 20 patients with classical osteosarcoma were chosen from the First Affiliated Hospital of Nanjing Medical University from January 2006 to December 2014.Every patient was under follow-up ranging from 12 months to 72 months and the middle follow-up time was 42 months.Then,the clinical features were analyzed.Every tumor specimen was treated with immunohistochemistry to examine the expression of PD-1 and PD-L1,and analyze the correlation between them and clinical characteristics of patients.Result: Of the 8 patients with ESOS,5 cases were males and 3 cases were females.The average age was 57.6 years.Six patients received MAP(high-dose methotrexate,doxorubicin,cisplatin)which is the first-line chemotherapy for classical osteosarcoma after surgery.There were 4 patients with distant metastasis by the end of follow-up,and the 5-year survival rate was 37.5%.Of the 20 cases of osteosarcoma,there were 11 males and 9 females.The average age was 19.1 years.Fourteen patients underwent postoperative MAP regimen chemotherapy.A total of 6 patients had distant metastases by the end of follow-up.The 5-year survival rate was 75%.There was a statistically significant difference in 5-year survival rates between the two groups(P<0.05).The positive rate of PD-L1 in patients with osteosarcoma(62.5%)was slightly higher than that in patients with osteosarcoma(40%),but there was no significant statistical difference(P>0.05).The positive expression of PD-L1 may be related to the progression(metastasis)of ESOS,but not to gender,age,tumor size.The positive expression of PD-L1 in OS patients was correlated with the stage of tumor.The positive rate of PD-L1 in stage ? OS patients was higher than that in other OS patients(P<0.05).PD-L1 positive patients had a worse prognosis than PD-L1 negative patients(P<0.05).Conclusion: The age of ESOS patients was older than OS patients,and there was no significant difference in the clinical features between ESOS and OS,such as gender and tumor site.The 5-year survival rate of ESOS patients was worse than that of OS.The expression of PD-L1 is up-regulated in ESOS and the positive rate of PD-L1 in patients with metastatic and positive margins is further increased.The expression of PD-L1 may be negatively correlated with the prognosis of ESOS.