PDF herunterladen
Horm Metab Res 2009; 41(9): 715-719
DOI: 10.1055/s-0029-1238274
Mini-Review

© Georg Thieme Verlag KG Stuttgart · New York

Pheochromocytomas, PASS, and Immunohistochemistry

E. Carlsen1 , Z. Abdullah2 , S. M. B. Kazmi2 , G. Kousparos1
  • 1Department of Pathology, Barts and the London NHS Trust, London, UK
  • 2ICMS/Barts School of Medicine and Dentistry, Queen Mary University of London, London, UK
Weitere Informationen

Publikationsverlauf

received 15.12.2008

accepted 11.08.2009

Publikationsdatum:
28. August 2009 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Differentiation between malignant and benign pheochromocytomas of the adrenal gland traditionally relies on the presence of clinically detectable metastases. The PASS system for differentiating between benign and malignant pheochromocytomas is based on defined morphological criteria, of which some are related to tumour cell proliferation and survival. Immunohistochemical markers for important events in the cell cycle were explored in order to characterise differences in apoptosis, G1 checkpoints, and S phase in more detail. A panel consisting of p53, tenascin, bcl-2, pRb, cyclin D1, mcm2, and p27 was employed. Only for pRb a statistically significant difference between PASS 3 and less and PASS 4+ tumours was detected, indicating qualitative differences in the mitotic cycle, probably immediately before early S phase. These results are discussed in relation to similar studies in recent literature.

Key words

pheochromocytoma - PASS - p53 - Rb - cyclin D - bcl-2 - tenascin - mcm2 - p27

References

  • 1 Thompson LDR, Young Jr WF, Kawashima A, Komminoth P, Tischler AS. Malignant adrenal phaeochromocytoma. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) Pathology and Genetics of Tumours of Endocrine Organs. Kleihues P, Sobin LH (series eds) World Health Organisation Classification of Tumours, Lyon, France: IARC Press 2004: 147-150
    Google Scholar
  • 2 Thompson LDR. Phaeochromocytomas of the Adrenal gland Scaled Score (PASS) to separate benign from malignant Neoplasms: A clinicopathological and immuno-phenotypic study of 100 cases.  Am J Surg Pathol. 2002;  26 551-556
    Google Scholar
  • 3 Ramesh GT, Manna SK, Aggarwal BB, Jadhav AL. Lead activates nuclear transcription factor-kappa B, activator protein-1, and amino-terminal c-Jun kinase in phaeochromocytoma cells.  Toxicol Appl Pharmacol. 1999;  155 280-286
    Google Scholar
  • 4 Lam KY, Lo CY, Wat NM, Luk JM, Lam KS. The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas.  J Clin Pathol. 2001;  54 443-448
    Google Scholar
  • 5 Gupta D, Shidham V, Holden J, Layfield L. Prognostic value of immunohistochemical expression of topoisomerase alpha II, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu in adrenal and extra-adrenal phaeochromocytomas.  Appl Immunohistochem Mol Morphol. 2000;  8 267-274
    Google Scholar
  • 6 Salmenkivi K, Heikkila P, Haglund C, Louhimo J, Arola J. Lack of histologically suspicious features, proliferative activity, and p53 expression suggest benign diagnosis in phaeochromocytomas.  Histopathology. 2003;  43 62-71
    Google Scholar
  • 7 Saraste A, Pulkki K. Morphologic and biochemical hallmarks of apoptosis.  Cardiovas Res. 2000;  45 528-537
    Google Scholar
  • 8 Cobrinik D, Francis RO, Abramson DH, Lee TC. Rb induces a proliferative arrest and curtails Brn-2 expression in retinoblastoma cells.  Mol Cancer. 2006;  5 72
    Google Scholar
  • 9 Cetani F, Pardi E, Viacava P, Viacava P, Pollina GD, Fanelli G, Picone A, Borsari S, Gazzerro E, Miccoli P, Berti P, Pinchera A, Marcocci C. A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer.  Clin Endocrinol (Oxf). 2004;  60 99-106
    Google Scholar
  • 10 Yang Y, Wenjun B, Haegebarth A, Tyner AL. Differential Regulation of D-Type Cyclins in the Mouse Intestine.  Cell Cycle. 2006;  5 180-183
    Google Scholar
  • 11 Wang DG, Johnston CF, Marley JJ, Phenix KV, Atkinson AB, Russell CFJ, Buchanan KD. Expression of the apoptosis- suppressing gene bcl-2 phaeochromocytomas is associated with the expression of c-myc.  J Clin Endorinol Metab. 1997;  82 1949-1952
    Google Scholar
  • 12 Hanahan D, Weinberg RA. The Hallmarks of Cancer.  Cell. 200;  100 57-70
    Google Scholar
  • 13 Hockenberry DM, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death.  Nature. 1990;  348 334-336
    Google Scholar
  • 14 Chang F, Syrjanen S, Tervahauta A, Syrjanen K. Tumorigenesis associated with p53 tumour suppressor gene.  Br J Cancer. 1993;  68 653-661
    Google Scholar
  • 15 Reed JC, Meister L, Tanaka S, Cuddy M, Yum S, Geyer C, Pleasure D. Differential expression of Bcl-2 proto-oncogene in neuroblastoma and other human tumour cell lines of neural origin.  Cancer Res. 1991;  51 6529-6538
    Google Scholar
  • 16 Wang DG, Johnston CF, Marley JJ, Phenix KV, Atkinson AB, Russell CFJ, Buchanan KD. Expression of the apoptosis- suppressing gene bcl-2 phaeochromocytoma is associated with the expression of c-myc.  J Clin Endorinol Metab. 1997;  82 1949-1952
    Google Scholar
  • 17 Chiquet-Ehrismann R, Mackie EJ, Pearson CA, Sakakura T. Tenascin: extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis.  Cell. 1986;  47 131-139
    Google Scholar
  • 18 Salmenkivi K, Heikkila P, Haglund C, Arola J. Malignancy in Phaeochromocytomas.  APMIS. 2004;  112 551-559
    Google Scholar
  • 19 Kimura N, Watanabe T, Noshiro T, Shizawa S, Miura Y. Histological grading of adrenal and extra-adrenal phaeochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal phaeochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors.  Endocr Pathol. 2005;  16 23-32
    Google Scholar
  • 20 August C, August K, Schroeder S. CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from non-metastasized sporadic phaeochromocytomas.  Modern Pathol. 2004;  17 1119-1128
    Google Scholar
  • 21 Liu TH, Chen YJ, Wu SF, Gao J, Jiang WJ, Lu ZH, Guan J, Wei SZ, Luo YF, Cao JL, Wan JW. Distinction between benign and malignant phaeochromocytomas.  Zhonghua Bing Li Xue Za Zhi. 2004;  33 198-202
    Google Scholar
  • 22 Kajor M, Ziaja J, Lange D, Król R, Ciupiñska-Kajor M, Turska-d’Amico M, Maka B, Cierpka L. Analysis of morphology of adrenal phaeochromocytoma as regards their potential malignancy.  Endokrynol Pol. 2005;  56 911-916
    Google Scholar
  • 23 Sporny S, Musiał J. Markers of malignancy in phaeochromocytomas.  Endokrynol Pol. 2005;  56 946-951
    Google Scholar
  • 24 Gao B, Meng F, Bian W, Chen J, Zhao H, Ma G, Shi B, Zhang J, Liu Y, Xu Z. Development and validation of phaeochromocytoma of the adrenal gland scaled score for predicting malignant phaeochromocytomas.  Urology. 2006;  68 282-286
    Google Scholar
  • 25 Bilek R, Safarik L, Ciprova V, Vlcek P, Lisa L. Chromogranin A, a Member of Neuroendocrine Secretory Proteins as a Selective Marker for Laboratory Diagnosis of Phaeochromocytoma.  Physiol Res. 2008;  57 ((Suppl 1)) S171-S179
    Google Scholar
  • 26 Strong VE, Kennedy T, Al-Ahmadie H, Tang L, Coleman J, Fong Y, Brennan M, Ghossein RA. Prognostic indicators of malignancy in adrenal phaeochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis.  Surgery. 2008;  143 759-768
    Google Scholar
  • 27 Anonymous . http://mitel.dimi.uniud.it/udipath/tpdb/show.php?id=94%20&%20view=%20accessed%20231008
  • 28 McNicol AM. Personal communication. 2008; 
  • 29 Eisenhofer G, Bornstein SR, Brouwers FM, Cheung NK, Dahia PL, de Krijger RR, Giordano TJ, Greene LA, Goldstein DS, Lehnert H, Manger WM, Maris JM, Neumann HP, Pacak K, Shulkin BL, Smith DI, Tischler AS, Young WF Jr. Malignant pheochromocytoma: current status and initiatives for future progress.  Endocr Relat Cancer. 2004;  11 423-436
    Google Scholar
  • 30 Favier J, Plouin PF, Corvol P, Gasc JM. Angiogenesis and vascular architecture in phaeochromocytomas: distinctive traits in malignant tumors.  Am J Pathol. 2002;  161 1235-1246
    Google Scholar
  • 31 Cryns VL, Thor A, Xu H-J, Hu SX, Wierman ME, Vickery  Jr AL, Benedict WF, Arnold A. Loss of the retinoblastoma tumor suppressor gene in parathyroid carcinoma.  N Engl J Med. 1994;  330 757-761
    Google Scholar
  • 32 Dotzenrath C, The BT, Farnebo F, Cupisti K, Svensson A, Toell A, Goretzki P, Larsson C. Allelic Loss of the Retinoblastoma Tumor Suppressor Gene: A Marker for Aggressive Parathyroid Tumors?.  J Clin Endocrinol Metab. 1996;  81 3194-3196
    Google Scholar
  • 33 de Krijger RD, v d Harst ED, Ham FD, Stijnen T, Dinjens WN, Koper JW, Bruining HA, Lamberts SW, Bosman FT. Prognostic value of p53, bcl-2, and c-erbB-2 protein expression in phaeochromocytomas.  J Pathol. 1999;  188 51-55
    Google Scholar
  • 34 Dahia PL, Aguiar RC, Tsanaclis AM, Bendit I, Bydlowski SP, Abelin NM, Toledo SP. Molecular and immuno-histochemical analysis of p53 in phaeochromocytomas.  Br J Cancer. 1995;  72 1211-1213
    Google Scholar
  • 35 Clarke MR, Weyant RJ, Watson CG, Carty SE. Prognostic markers in phaeo-chromocytoma.  Hum Pathol. 1998;  29 522-526
    Google Scholar
  • 36 Thompson LDR. Personal communication. 2006; 
  • 37 Tischler AS, Kimura N, Mcnicol AM. Pathology of phaeochromocytoma and extra-adrenal paraganglioma.  Ann N Y Acad Sci. 2006;  1073 557-570
    Google Scholar

Correspondence

Dr. E. Carlsen

1 Badgers Bank

Ipswich

Suffolk IP2 9EN

UK

Telefon: 0044/14/7368 32 32

eMail: eivindcarlsen49@hotmail.com

      >