Expression and significance of nitric oxide synthase mRNAs and proteins in giant cell tumors of bone

BACKGROUND & OBJECTIVE: Recent studies have indicated that nitric oxide (NO) plays an important role in carcinogenesis and tumor progression. Activity of nitric oxide synthase (NOS) has been detected in normal bone cell lines. There was no report about relation of expression of NOS in giant cell tumors(GCT) of bone with its pathological grading and tumor recurrence. This study was designed to investigate the relationship amoung expression of NOS mRNAs, NOS proteins, pathological grading and tumor recurrence. METHODS: In situ hybridization (ISH) with cDNA probe was used to determine 14 frozen GCT specimens for constitutive NOS(cNOS) mRNA and inducible NOS(iNOS) mRNA. Immunohistochemical (IHC) staining with multiclonal antibodies was used to determine 42 paraffin-embedded GCT specimens for protein expression of NOS1, NOS2, and NOS3. RESULTS: (1)In 14 frozen GCT specimens, the positive expression rates of cNOS and iNOS mRNAs of multinuclear giant cells (MGC) were 78.6% and 57.1%; the positive expression rates of cNOS and iNOS mRNAs in mononuclear cells (MC) were both 35.7%. (2)The positive expression rate of cNOS mRNA in MGC of groups grading II and III was significantly higher than that of group grading I (P=0.008). (3) In 42 paraffin-embedded GCT specimens, the positive expression rates of NOS1, NOS2, and NOS3 protein were 85.7%, 59.5%, and 31.0% in MGC, 54.8%, 28.6%, and 14.3% in MC, respectively. (4)The positive expression rate of NOS1 protein in MC of groups grading II, III was significantly higher than that of group grading I (P=0.006). (5)The positive expression rate of NOS1 protein in MC of the recurrent group was significantly higher than that of the non-recurrent group (P=0.018). The positive expression rate of NOS3 protein in MGC of recurrent group was significantly higher than that of the non-recurrent group (P=0.041). CONCLUSION: The expression of NOS in GCT,especially cNOS in MC, is closely related to the pathological grading and the recurrence of GCT.