Demonstration of Biological Aggressiveness of Bone Giant Cell Tumor by the Comparative Study of Immunohistochemical Detection of DNA-instability and Cortical Bone Destruction by CT.

Abstract

The degree of DNA-instability as revealed by the immunohistochemical staining with anti-single-stranded DNA antibody after acid hydrolysis (DNA-instability test) was used as a marker of malignancy. This was applied to benign (4 osteochondroma and 4 enchondroma cases), border-line (23 bone giant cell tumor, BGCT cases), and malignant (6 chondrosarcoma and 6 osteosarcoma cases) neoplastic lesions. The expression of tumor oncogene, c-myc was detected immunohistochemically. Proliferative activity was evaluated by PCNA-immunohistochemistry, and the quantitative analysis of the number, mean area, mean total area, the largest area, and maximum shape-irregularity of AgNORs in a nucleus were performed for all these cases. The results for 19 BGCT (82.6%) cases, 6 chondrosarcoma cases (100%), and 6 osteosarcoma cases (100%) were positive with the DNA-instability test, indicating their malignancy. All benign tumor cases were negative with the DNA-instability test. Reflecting the malignant character, all chondrosarcoma cases, all osteosarcoma cases and the BGCT cases positive with the DNA-instability test showed statistically highervalues of PCNA-index; and all AgNORsparameters in comparison to those for benign tumor cases, and c-myc was positive for 66.7%, and 26.3%, of them, respectively.But these values for BGCT with positive and negative DNA-instability test results showed no statistically meaningful differences, All the BGCT cases negative with DNA-instability test were negative for c-myc expression. Among the BGCT cases positive with DNA-instability test, 18 cases (94.7%) showed cortical bone destruction by computed tomography (CT), and 5 cases (26.3%) showed extra-osseous expansion. No such radiographic changes were detected among the BGCT cases negative with DNA-instability test.Among 18 BGCT cases with cortical bone destruction, 5 cases (27.8%) showed tumor recurrences, and 2 cases (11.1%) showed lung metastases. These results indicate that the majority of BGCT cases are malignant and the detection of cortical bone destruction by CT is a sensitive clinical marker to detect them.