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Relationship Between P15 Gene Mutation and Formation and Metastasis of Malignant Osteosarcoma

ChangShui Yu, WenBo Wang

Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland)

Med Sci Monit 2016; 22:656-661

DOI: 10.12659/MSM.895022

Available online:

Published: 2016-02-27

BACKGROUND: As a type of primary malignant bone tumor, osteosarcoma has high incidence and poor prognosis, and is predisposed for pulmonary metastasis. The abnormal expression of P15 gene directly participates in the invasion of various cancers. Therefore, this study investigated the gene mutation of P15 in both primary lesion and pulmonary metastasis lesion of osteosarcoma in a rat model, in an attempt to elucidate the value of P15 gene as a biological marker.
MATERIAL AND METHODS: A total of 60 SD rats were randomly divided into 2 groups. Model rats had injection of osteosarcoma UMR-106 cells (5×106) inoculated underneath the right forelimb skin, while control rats received saline injection instead. Six rats were sacrificed after 0, 1, 2, 4, and 6 weeks of the inoculation. Tissue samples from inoculation sites and lungs were extracted for measuring the tumor size. SP immunohistochemical (IHC) staining was used to detect the positive expression rate, while P15 gene mutation was detected by PCR method.
RESULTS: With the elongation of inoculation time, tumor size was significantly increased (p<0.05). The positive expression rates in both primary and pulmonary metastasis lesions were also significantly elevated (p<0.05). The occurrence rate of P15 gene mutation in model rats was significantly elevated and showed a correlation with the tumor formation (r=0.998, p<0.05).
CONCLUSIONS: The P15 gene mutation was significantly correlated with osteosarcoma formation and metastasis towards the pulmonary tissue, suggesting its potency as a novel biological marker for early diagnosis of osteosarcoma.

Keywords: Blood Cells - metabolism, Animals, Bone Neoplasms - pathology, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p15 - genetics, Lung Neoplasms - secondary, Mutation - genetics, Neoplasm Metastasis, Osteosarcoma - pathology, Polymerase Chain Reaction, Rats, Sprague-Dawley, Tumor Burden