Expression of cyclin A in soft tissue sarcomas correlates with tumor aggressiveness.

Cyclins and cyclin-dependent kinases regulate the cell cycle. Cyclin A has a dual role in cell proliferation. It is essential in the S phase for DNA replication, and it is also involved in G2-M-phase transition, signifying actively dividing cells. The expression of cyclin A was determined by immunohistochemistry in paraffin sections of 126 soft tissue sarcomas. The median cyclin A score was 10.8% (range, 1-54%). Cyclin A expression correlated with the S-phase fraction, Ki-67 score, G2-M phase, and grade. It did not correlate with the size of the tumor. A high cyclin A score predicted a poor metastasis-free survival (P < 0.01) and a poor disease-specific overall survival (P = 0.01). We concluded that the expression of cyclin A is a powerful prognostic factor in soft tissue sarcoma. Moreover, the cyclin A score determines the fraction of tumor cells in the S phase and the G2 phase, which are the most sensitive cell cycle phases for current modalities of cancer treatment.

Surgical treatment of myeloma of bone.

33 patients treated operatively for plasma cell disease were analysed. There were 21 men and 12 women with an average age of 54 years. There was an undefined bone tumour in 23 cases, and a pathologic fracture in 10 cases. In only 6 cases was the diagnosis known before the operation. The primary tumour localisations were: vertebral column in 13, pelvis in 7, femur in 6, humerus in 2, rib in 1, tibia in 1, fibula in 1, scapula in 1 and olecranon in 1 case. 16 diagnostic biopsies were taken. Vertebral tumours were mainly evacuated or decompressed, combined with a stabilising procedure in 8 cases. A total of six endoprostheses, five to the femur and one to the humerus were performed. Two primarily wide resections, to the fibula and to the scapula were done. There were no locally recurring tumours during a mean follow-up time of 4 years and 2 months, and we conclude that operative and oncologic treatment is successful in providing the patient with a stable, pain-free locomotive system.

A high proliferation rate measured by cyclin A predicts a favourable chemotherapy response in soft tissue sarcoma patients.

A small but not insignificant number of patients experience a prolonged survival after treatment of metastatic soft tissue sarcoma. This must be weighed against the majority of the patients who benefit little from the therapy, but nevertheless experience its side-effects. It would therefore be of utmost importance to be able to screen for those patients who respond to the treatment. Since proliferating cells are more sensitive to chemotherapy than non-proliferative cells, we measured the proliferation rate of the primary tumour of 55 soft tissue sarcoma patients with locally advanced or metastatic disease by determining the flow cytometric S phase fraction and immunohistochemical Ki-67 and cyclin A scores. S phase fraction or Ki-67 score did not predict chemotherapy response or progression-free survival. A high cyclin A score, however, correlated with a better chemotherapy response (P = 0.02) and longer progression-free survival time (P = 0.04). Our results suggest that a high cyclin A score predicts chemotherapy sensitivity.

Comparison of the Ki-67 score and S-phase fraction as prognostic variables in soft-tissue sarcoma.

Immunohistochemically determined Ki-67 scores and flow cytometrically determined S-phase fractions were successfully evaluated from the primary tumours of 123 patients with soft-tissue sarcoma. All patients had either limb or superficial trunk tumours. Ki-67 score correlated strongly with ploidy, S-phase fraction and grade. Ki-67 did not correlate with the size of the primary tumour. When analysed as a continuous variable, Ki-67 was a stronger predictor of both metastasis-free survival and disease-specific overall survival (P = 0.003 and 0.04 respectively) than was the S-phase fraction (P = 0.06 and 0.07 respectively). We tested the relevance of different cut-point values by dividing the whole material into two parts at every 10% (e.g. 10% of patients vs. the remaining 90%, 20% vs. 80%, etc.). We counted the relative risk and confidence interval at all these cut-off points. Ki-67 had good prognostic discriminating power irrespective of the cut-point value, but S-phase fraction lost its prognostic power at higher cut-point values. In conclusion, we found that Ki-67 is a useful prognostic tool in the treatment of soft-tissue sarcoma patients irrespective of the cut-point value. S-phase fraction can be used at lower cut-point values.