Subscribe to RSS
DOI: 10.1055/s-0029-1238274
© Georg Thieme Verlag KG Stuttgart · New York
Pheochromocytomas, PASS, and Immunohistochemistry
Publication History
received 15.12.2008
accepted 11.08.2009
Publication Date:
28 August 2009 (online)

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: 147-150MissingFormLabel - 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 7
Saraste A, Pulkki K.
Morphologic and biochemical hallmarks of apoptosis.
Cardiovas Res.
2000;
45
528-537
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 12
Hanahan D, Weinberg RA.
The Hallmarks of Cancer.
Cell.
200;
100
57-70
MissingFormLabel
- 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
MissingFormLabel
- 14
Chang F, Syrjanen S, Tervahauta A, Syrjanen K.
Tumorigenesis associated with p53 tumour suppressor gene.
Br J Cancer.
1993;
68
653-661
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 18
Salmenkivi K, Heikkila P, Haglund C, Arola J.
Malignancy in Phaeochromocytomas.
APMIS.
2004;
112
551-559
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 23
Sporny S, Musiał J.
Markers of malignancy in phaeochromocytomas.
Endokrynol Pol.
2005;
56
946-951
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 27
Anonymous
.
http://mitel.dimi.uniud.it/udipath/tpdb/show.php?id=94%20&%20view=%20accessed%20231008
MissingFormLabel
- 28
McNicol AM.
Personal communication.
2008;
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 35
Clarke MR, Weyant RJ, Watson CG, Carty SE.
Prognostic markers in phaeo-chromocytoma.
Hum Pathol.
1998;
29
522-526
MissingFormLabel
- 36
Thompson LDR.
Personal communication.
2006;
MissingFormLabel
- 37
Tischler AS, Kimura N, Mcnicol AM.
Pathology of phaeochromocytoma and extra-adrenal paraganglioma.
Ann N Y Acad Sci.
2006;
1073
557-570
MissingFormLabel
Correspondence
Dr. E. Carlsen
1 Badgers Bank
Ipswich
Suffolk IP2 9EN
UK
Phone: 0044/14/7368 32 32
Email: eivindcarlsen49@hotmail.com