title: Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases?
abstract: Evaluation of the malignant potential of phaeochromocytomas in the absence of metastases presents a formidable challenge to both clinicians and pathologists. Until now, no widely accepted clinical, histological, immunohistochemical or molecular method has become available to discriminate malignant from benign phaeochromocytomas. In other endocrine tumours, estimation of proliferative activity by MIB-1 immunostaining has emerged as a promising approach for the determination of metastatic potential. In this study, the utility of MIB-1 immunostaining as a predictive marker for the occurrence of metastases in phaeochromocytomas was evaluated. In addition, the density of S100-positive sustentacular cells was studied, since their depletion has been identified as a negative predictive marker in smaller series. Furthermore, several clinicopathological parameters were evaluated. One hundred and ten patients operated on for a total of 99 benign and 37 malignant phaeochromocytomas were studied. All malignant tumours had documented metastases. The histopathological diagnosis of primary tumours and metastases was reviewed and graded for angioinvasion, capsular extension, and intra-tumoural necrosis. The proliferative index (percentage of MIB-1-positive cells) and the density of S100-positive cells were assessed. In addition, age at resection, associated familial tumour syndromes, tumour size, and tumour location were recorded. Univariate analysis revealed statistically significant correlations between malignancy and proliferative index (p<0.0005) and depletion of S100-positive sustentacular cells (p<0.0005). Fifty per cent of the malignant, but none of the benign phaeochromocytomas had a proliferative index greater than 2.5%. Higher age at resection (p=0. 03), sporadic occurrence (p<0.0005), extra-adrenal location (p<0. 0005), tumour size (p<0.0005), and necrosis (p=0.03) were also significantly associated with malignancy. Logistic regression showed that proliferative index (p=0.0072), size (p=0.0022), and extra-adrenal location (p=0.0012) of the primary tumour were independently predictive for malignancy. In conclusion, this study indicates that assessing the proliferative activity of phaeochromocytomas by MIB-1 immunohistochemistry can predict the occurrence of metastases. The predictive value of S100 immunostaining, tumour size, and extra-adrenal location of the tumour was also confirmed.
authors.affiliation: Department of Surgery, Erasmus University Hospital, Rotterdam, The Netherlands. vanderharst@hlkd.azr.nl
authors.forename: E
authors.initials: E
authors.lastname: van der Harst
authors.forename: H A
authors.initials: HA
authors.lastname: Bruining
authors.forename: H
authors.initials: H
authors.lastname: Jaap Bonjer
authors.forename: F
authors.initials: F
authors.lastname: van der Ham
authors.forename: W N
authors.initials: WN
authors.lastname: Dinjens
authors.forename: S W
authors.initials: SW
authors.lastname: Lamberts
authors.forename: W W
authors.initials: WW
authors.lastname: de Herder
authors.forename: J W
authors.initials: JW
authors.lastname: Koper
authors.forename: T
authors.initials: T
authors.lastname: Stijnen
authors.forename: C
authors.initials: C
authors.lastname: Proye
authors.forename: M
authors.initials: M
authors.lastname: Lecomte-Houcke
authors.forename: F T
authors.initials: FT
authors.lastname: Bosman
authors.forename: R R
authors.initials: RR
authors.lastname: de Krijger
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000276:immunology; D002471:Cell Transformation, Neoplastic; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D010673:Pheochromocytoma / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D012044:Regression Analysis
chemical_list: D018797:Cell Cycle Proteins