Document Detail

CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from nonmetastasized sporadic pheochromocytomas.
MedLine Citation:
PMID:  15167935     Owner:  NLM     Status:  MEDLINE    
The natural course of pheochromocytomas (PCC) cannot be predicted for certain on the basis of primary histology, their malignant character can only be confirmed by the occurrence of metastases during follow-up. Based on the recently proposed PASS score for evaluation we examined 37 adrenal (36 sporadic and one familial) and six sporadic extra-adrenal paragangliomas (all designated as pheochromocytomas) with a 'malignant histology' to find additional predictive factors. Drawing upon the follow-up (18 months to 12 years, mean 5.8 years) metastasized (n=20) and nonmetastasized (n=23) courses could be distinguished. Metastasized PCC revealed significantly (P=0.03) more copy number changes on comparative genomic hybridization (CGH) (mean 8.3) than nonmetastasized tumors (mean: 4.3). The most frequent chromosomal alterations were losses on 1p (75.6%) and 3q (44%). Both were detected with identical frequency in metastasized and nonmetastasized PCC. A gain on 17q (P=0.025) was significantly predominant in malignant courses and suggests similarities in the genetic origin and progression of PCC and neuroblastomas. The proliferative activity (MIB-1 score) of metastasized PCC (n=20) was found to be significantly higher in metastasized tumors (mean 12.8% vs mean 3.5%). In contrast, the semiquantitatively scored membrane-bound staining of CD 44-S was stronger in tumors without metastases (mean 2.1 vs mean: 0.25) during the follow-up period (P<0.01). Although the results correspond to the established weight differences the tumor weight does not appear to be an independent prognostic factor. Our study suggests that CD 44-S and MIB-1 immunostaining as well as the CGH results might complement the PASS score in predicting a metastasized course of PCC. Regardless of tumor weight, tumors with a 'malignant histology' are highly prone to metastasize when more than 5% of MIB1-positive nuclei are present or CD44-S immunostaining is negative, or both. PCC with 10 or more copy number changes on CGH must be referred to as malignant tumors.
Christian August; Kathrein August; Soeren Schroeder; Hannes Bahn; Raoul Hinze; Hideo A Baba; Christian Kersting; Horst Buerger
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc     Volume:  17     ISSN:  0893-3952     ISO Abbreviation:  Mod. Pathol.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-17     Completed Date:  2005-01-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8806605     Medline TA:  Mod Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1119-28     Citation Subset:  IM    
Institute of Pathology, University Muenster, Germany.
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MeSH Terms
Adrenal Gland Neoplasms / genetics,  metabolism,  pathology*
Aged, 80 and over
Antigens, CD44 / analysis*
Chromosome Aberrations
Diagnosis, Differential
Ki-67 Antigen / analysis*
Middle Aged
Neoplasm Metastasis / diagnosis*
Nucleic Acid Hybridization / methods*
Pheochromocytoma / genetics,  metabolism,  pathology*
Reg. No./Substance:
0/Antigens, CD44; 0/Ki-67 Antigen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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