Apoptotic and proliferative markers in chordomas: a study of 26 tumors.

Abstract

Few studies have examined the role of cell proliferation and apoptotic markers in chordomas. This study retrospectively reviews the clinicopathologic features of 26 chordomas and examines MIB-1, p53, bcl-2, and cyclin D1 immunoreactivity in these neoplasms. Patients ranged in age from 34 to 78 years (mean, 60.7 years) and included 14 females. The most common presentations included lower back pain (N = 15) and headaches (N = 10). Sixteen tumors arose in the lumbosacral region and 10 in the clivus. Initial surgery included biopsy (N = 17), subtotal resection (N = 4), and gross total resection (N = 5). The single highest mitosis count per 10 high power fields ranged from 0 to 6 (mean, 1). Marked nuclear pleomorphism was identified in seven tumors. Marked hypercellularity was seen in two tumors. Focal necrosis was identified in seven tumors. MIB-1 labeling indices (LI) in 22 tumors ranged from 0 to 3.8 (mean, 0.5). Cyclin D1 LI ranged from 0 to 82.4 (mean, 35.6). Seven tumors had positive p53 immunostaining and three demonstrated focal positive staining with bcl-2 antibody. Five tumors locally recurred; two patients developed metastatic disease. Thirteen patients received adjuvant chemotherapy and/or radiation therapy. At last known follow-up, seven patients died with tumor (12 to 132 months follow-up). Five additional patients died, two without tumor at 36 and 72 months follow-up and three patients in whom the tumor status at death was not known. Seven patients were alive with evidence of tumor (1 to 120 months) and five patients were alive without evidence of tumor (12 to 84 months). Clinical follow-up was not available in one patient. In conclusion, the low MIB-1 LIs and the lack of p53 and bcl-2 staining is in keeping with the low-grade nature of most chordomas. High cyclin D1 LIs may be reflective of a tendency to accumulate cyclin D1 protein; however, there appears to be a block in the effect of cyclin D1 on cell proliferation in these tumors. Cyclin D1, MIB-1, p53, and bcl-2 immunostaining does not appear to improve one's ability to predict behavior versus routine light microscopy.