The role of prognostic markers (MiB-1, RB, and bcl-2) in the diagnosis of parathyroid tumors

Assessment of the malignant potential of parathyroid tumors in the absence of metastasis can be difficult using morphologic criteria alone. The role of prognostic markers that may assist in evaluating aggressive behavior in these tumors has not been fully studied. We performed a retrospective study of 31 parathyroid lesions, including 10 adenomas, 10 atypical lesions, and 11 carcinomas, to evaluate the diagnostic and prognostic role of the MiB-1, p53, RB, and bcl-2 markers by immunohistochemical techniques. The mean tumor proliferative fraction (TPF), expressed as the number of MiB-1-positive nuclei per 1000 cells, was 20.3 in adenomas (range, 5-51), 20.0 in atypical lesions (range, 8-36), and 79.8 in carcinomas (range, 4-133). Only 1 of 20 benign lesions had a TPF more than 40, and only 2 of 11 carcinomas had a TPF less than 40. One atypical lesion and two carcinomas showed scattered cells positive for p53. Patients with the adenoma with increased TPF and the atypical lesion with positive p53 have been free of disease for 16 months. bcl-2 was expressed in 7 (70%) of 10 adenomas, 2 (20%) of 10 atypical lesions, and 4 (36%) of 11 carcinomas. Two Of the 11 carcinomas were RB negative, whereas all of the 20 benign lesions were RB positive. We conclude that high TPF (greater than 40 as measured by staining with MiB-1) strongly correlates with malignancy and, therefore, may be useful in the diagnosis of carcinomas. Negative RB stain, although not a common event, may be helpful to exclude benign lesions. Other tumor markers (p53 and bcl-2) were not useful in distinguishing malignant from benign lesions.