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Background. The availability of Ki-67 monoclonal antibody has opened new possibilities for an extensive analysis of cell kinetics in human neoplasms. Ki-67 antibody reveals a nuclear antigen that is expressed in proliferating but not in quiescent cells. Although the reliability of Ki-67 immunostaining has been evaluated in different tumor types, little information has been reported on bone neoplasms. Methods. Cell proliferation, as determined by Ki-67 expression, was measured by immunofluorescence on representative cytospins obtained from 205 patients with bone tumors. In each sample, the percentage of Ki-67-positive cells was quantified on at least 500 cells and expressed as Ki-67 labeling index (LI). Results. Ki-67 LI was lower in benign and low grade lesions as compared with high grade malignant lesions. A correlation between Ki-67 LI and histologic grade was observed in osteosarcoma and chondrosarcoma. In osteosarcoma, among the 43 primary lesions included in this study, 30 patients, all treated with the same regimen of chemotherapy and limb-salvage surgery, were selected to establish the prognostic significance of cell proliferation. The Ki-67 labeling was higher in patients with a good histologic response to chemotherapy. However, at a 24-month follow-up, a worse prognosis was associated with a higher proliferative activity, whereas no correspondence was found between the histologic response to preoperative chemotherapy and the disease free survival, suggesting that in high grade osteosarcoma the biologic aggressiveness expressed by high levels of Ki-67 LI may be clinically more relevant than the responsiveness to antineoplastic agents. Conclusions. In bone tumors, the level of Ki-67 expression correlates with the level of malignancy and is diagnostically and prognostically useful.

Background. Malignant fibrous histiocytoma (MFH) of bone is a rare bone tumor, and its prognosis has been controversial. Methods. Thirty-four patients with MFH of bone were examined clinicopathologically for prognostic factors. Results. The most common skeletal site of the tumor was the femur (15 cases), followed by the pelvic bones (6 cases), tibia (5 cases), and fibula (5 cases). Of 29 patients available for follow-up, the 5-year survival rate of 17 who underwent adequate surgical treatment was 63%. The 5-year survival rate of the remaining 12 patients, including 5 with MFH of the pelvic bone who received inadequate or palliative surgery, was 17%. All six patients who received intensive chemotherapy combined with adequate surgical treatment were alive and well 5 years after the initial treatment. Histologically, the presence of desmoplasia and chronic inflammatory infiltration in the tumor tended to be prognostic indicators, although not to a statistically significant extent. Patients whose tumors contained wide areas of desmoplasia had a worse prognosis (5-year survival rate, 20%). In contrast, those with a prominent chronic inflammatory infiltrate had a 5-year survival rate of 78%. Conclusions. These histologic variables would be helpful for predicting the prognosis of MFH of bone. Adjuvant intensive chemotherapy combined with adequate initial surgery may effect a clinical cure. Cancer 1993; 72:1902-8.

Osteosarcoma is a form of bone cancer, and is especially common in younger people. The primary form of treatment is surgical removal of the affected bone, which often requires amputation of the limb. However, it has been found that the addition of adjuvant chemotherapy to the surgical treatment not only improves survival, but in some cases may make it possible for more conservative surgery and preservation of a limb. A study was conducted to evaluate the effectiveness of chemotherapy and surgery in the treatment of osteosarcoma; the study also evaluated patient and treatment factors which correlated with improved survival. Ninety-two patients, ranging in age from four to 28 years, were treated with cisplatin delivered into an artery. Twenty-eight patients showed sufficiently great responses to the chemotherapy that they were given extra courses of chemotherapy in hopes of making more conservative surgery possible. A week after the third infusion of cisplatin, the cancer was surgically removed, and after surgery the patients were treated with intravenous cisplatin and doxorubicin. It was possible to evaluate 62 surgical specimens. Tumor destruction greater than 90 percent was observed in 16 of 40 patients who received three or fewer chemotherapeutic courses prior to surgery and in 17 of 20 patients who received four or more. Conservative surgery was possible in 68 percent of the patients who received four or more courses, in contrast with only 23 percent of the patients who received fewer preoperative courses of chemotherapy. Metastatic spread of cancer to the lungs was common, affecting 36 patients; two patients developed metastatic cancer in other bones. A total of 46 patients - exactly half -remain free of disease at follow-up periods ranging from 18 to 78 months after diagnosis. Male patients suffered greater likelihood of recurrence and also greater likelihood of death from osteosarcoma. The degree of tumor necrosis, or tissue destruction, achieved after the preoperative chemotherapy was also predictive of recurrence; patients with low necrosis were more likely to suffer recurrence. The appearance of the tumor under the microscope also predicted the likelihood of recurrence, and cancers which did not have the classic appearance of osteosarcoma were more likely to recur. (Consumer Summary produced by Reliance Medical Information, Inc.)