Predicting metastasis of pheochromocytomas using DNA flow cytometry and immunohistochemical markers of cell proliferation - A positive correlation between MIB-1 staining and malignant tumor behavior

BACKGROUND. In the absence of metastases, there are no reliable microscopic features that distinguish malignant from benign pheochromocytomas. Because a common feature of malignancy is the loss of cell cycle regulation and no rmal growth arrest, the authors hypothesized that analysis of the cell cycl e could be used to aid in the diagnosis of malignant pheochromocytoma. METHODS. Cell cycle analysis of archival samples of 51 pheochromocytomas (4 0 sporadic, 11 familial) from 45 patients, including 6 malignant and 45 ben ign tumors, was conducted. Flow cytometry data and immunohistochemistry for markers of cell proliferation (proliferating cell nuclear antigen [PCNA] a nd MIB-1 [Ki-67]) were correlated with the authors' clinical data base reco rds, with a mean follow-up of 66 months. RESULTS. No correlation of DNA ploidy, S-phase fraction by flow cytometry, or PCNA with malignancy was observed. Staining for the MIB-1 nuclear prolif eration marker was positive in 3 of 6 (50%) of the malignant pheochromocyto mas and negative in all 45 benign tumors (P< 0.01). CONCLUSIONS. Contrary to some previous reports, a diploid DNA pattern does not necessarily predict benign behavior of pheochromocytoma. In this study, cell cycle analysis and, in particular, assessment of the MIB-1 nuclear pr oliferation marker was useful in the histologic evaluation of pheochromocyt oma, as MIB-1 was expressed only in malignant tumors. (C) 1999 American Can cer Society.