Abstract
Expression of the intermediate filament, nestin, was long believed to be restricted
to neuroectodermal stem cells. However, nestin expression has recently been detected
in several tumors. Since adrenocortical carcinoma, a tumor entity still very difficult
to classify, may gain the ability to aberrantly express neuroectodermal proteins including
chromogranin A and synaptophysin, we asked the question whether nestin might also
be detected in adrenocortical carcinomas, and if so, whether it might serve as a tool
for clinical pathology. Therefore, we studied the expression of nestin in normal adrenal
glands, adrenocortical adenomas, and adrenocortical cancers using specific immunohistochemistry
and semi-quantitative reverse transcriptase-polymerase chain reaction. Immunostaining
was nestin-positive in 1 out of 9 normal adrenal glands (11%), 2 out of 20 adrenocortical
adenomas (10%), and 13 out of 16 adrenocortical carcinomas (81%). Expression of nestin
mRNA could be detected in all microdissected tissues, independently of their grade
of dedifferentiation. We conclude that our findings provide further evidence that
nestin, as a marker, is not restricted to neuronal stem cells and nestin expression
is worth to be studied in adrenocortical tumors.
Key words
fetal adrenal gland - nestin - tumor - adrenal adenoma - adrenocortical carcinoma
References
1
Miettinen M.
Neuroendocrine differentiation in adrenocortical carcinoma. New immunohistochemical
findings supported by electron microscopy.
Lab Invest.
1992;
66
169-174
2
Tartour E, Caillou B, Tenenbaum F, Schroder S, Luciani S, Talbot M, Schlumberger M.
Immunohistochemical study of adrenocortical carcinoma. Predictive value of the D11
monoclonal antibody.
Cancer.
1993;
72
3296-3303
3
Haak HR, Fleuren GJ.
Neuroendocrine differentiation of adrenocortical tumors.
Cancer.
1995;
75
860-864
4
Komminoth P, Roth J, Schroder S, Saremaslani P, Heitz PU.
Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas
and adrenocortical carcinomas. Implications for the differential diagnosis of adrenal
gland tumors.
Lab Invest.
1995;
72
424-431
5
Liu AM, Maeda S, Hosone M, Azuma K, Katayama H, Yokoyama M.
Use of electron microscopic evaluation for the diagnosis of adrenal cortical carcinoma
in fine needle aspiration cytology: a case report and review of the literature.
Med Electron Microsc.
2001;
34
190-197
6
Stratakis CA, Carney JA, Kirschner LS, Willenberg HS, Brauer S, Ehrhart-Bornstein M,
Bornstein SR.
Synaptophysin immunoreactivity in primary pigmented nodular adrenocortical disease:
neuroendocrine properties of tumors associated with Carney complex.
J Clin Endocrinol Metab.
1999;
84
1122-1128
7
Bourdeau I, Lacroix A, Schurch W, Caron P, Antakly T, Stratakis CA.
Primary pigmented nodular adrenocortical disease: paradoxical responses of cortisol
secretion to dexamethasone occur in vitro and are associated with increased expression
of the glucocorticoid receptor.
J Clin Endocrinol Metab.
2003;
88
3931-3937
8
Weiss LM, Medeiros LJ, Vickery AL.
Pathologic features of prognostic significance in adrenocortical carcinoma.
Am J Surg Pathol.
1989;
13
202-206
9
Grumbach MM, Biller BM, Braunstein GD, Campbell KK, Carney JA, Godley PA, Harris EL,
Lee JK, Oertel YC, Posner MC, Schlechte JA, Wieand HS.
Management of the Clinically Inapparent Adrenal Mass (“Incidentaloma”).
Ann Intern Med.
2003;
138
424-430
10
Ho CL, Liem RK.
Intermediate filaments in the nervous system: implications in cancer.
Cancer Metastasis Rev.
1996;
15
483-497
11
Prasad S, Soldatenkov VA, Srinivasarao G, Dritschilo A.
Intermediate filament proteins during carcinogenesis and apoptosis.
Int J Oncol.
1999;
14
563-570
12
Lendahl U, Zimmerman LB, MacKay RD.
CNS stem cells express a new class of intermediate filament protein.
Cell.
1990;
60
585-595
13
Zimmerman L, Parr B, Lendahl U, Cunningham M, MacKay R, Gavin B, Mann J, Vassileva G,
MacMahon A.
Independent regulatory elements in the nestin gene direct transgene expression to
neural stem cells or muscle precursors.
Neuron.
1994;
12
11-24
14
Dahlstrand J, Lardelli M, Lendahl U.
Nestin mRNA expression correlates with the central nervous system progenitor cell
state in many, but not all, regions of developing central nervous system.
Brain Res Dev Brain Res.
1995;
84
109-129
15
Sejersen T, Lendahl U.
Transient expression of the intermediate filament nestin during skeletal muscle development.
J Cell Sci.
1993;
106
1291-1300
16
Kachinsky AM, Dominov JA, Miller JB.
Myogenesis and the intermediate filament protein, nestin.
Dev Biol.
1994;
165
216-228
17
Dahlstrand J, Collins VP, Lendahl U.
Expression of the class VI intermediate filament nestin in human central nervous system
tumors.
Cancer Res.
1992;
52
5334-5341
18
Tohyama T, Lee VM, Rorke LB, Marvin M, MacKay RD, Trojanowski JQ.
Nestin expression in embryonic human neuroepithelium and in human neuroepithelial
tumor cells.
Lab Invest.
1992;
66
303-313
19
Tohyama T, Lee VM, Rorke LB, Marvin M, MacKay RD, Trojanowski JQ.
Monoclonal antibodies to a rat nestin fusion protein recognize a 220-kDa polypeptide
in subsets of fetal and adult human central nervous system neurons and in primitive
neuroectodermal tumor cells.
Am J Pathol.
1993;
143
258-268
20
Kobayashi M, Sjoberg G, Soderhall S, Lendahl U, Sandstedt B, Sejersen T.
Pediatric rhabdomyosarcomas express the intermediate filament nestin.
Pediatr Res.
1998;
43
386-392
21
Smits A, van Grieken D, Hartman M, Lendahl U, Funa K, Nister M.
Coexpression of platelet-derived growth factor alpha and beta receptors on medulloblastomas
and other primitive neuroectodermal tumors is consistent with an immature stem cell
and neuronal derivation.
Lab Invest.
1996;
74
188-198
22
Tsujimura T, Makiishi-Shimobayashi C, Lundkvist J, Lendahl U, Nakasho K, Sugihara A,
Iwasaki T, Mano M, Yamada N, Yamashita K, Toyosaka A, Terada N.
Expression of the intermediate filament nestin in gastrointestinal stromal tumors
and interstitial cells of Cajal.
Am J Pathol.
2001;
158
817-823
23
Valtz NL, Hayes TE, Norregaard T, Liu SM, MacKay RD.
An embryonic origin for medulloblastoma.
New Biol.
1991;
3
364-371
24
Ehrhart-Bornstein M, Breidert M, Guadanucci P, Wozniak W, Bocian-Sobkowska J, Malendowicz LK,
Bornstein SR.
17 alpha-Hydroxylase and chromogranin A in 6th week human fetal adrenals.
Horm Metab Res.
1997;
29
30-32
25
Haase M, Schott M, Bornstein SR, Malendowicz LK, Scherbaum WA, Willenberg HS.
CITED2 is expressed in human adrenocortical cells and regulated by basic fibroblast
growth factor.
J Endocrinol.
2007;
192
459-465
26
Bertelli E, Regoli M, Lucattelli M, Bastianini A, Fonzi L.
Nestin expression in rat adrenal gland.
Histochem Cell Biol.
2002;
117
371-377
27
Willenberg HS, Walters R, Bornstein SR.
Use of laser microdissection in complex tissue.
Methods Enzymol.
2002;
356
216-223
28
Latronico AC, Almeida MQ.
The molecular pathogenesis of childhood adrenocortical tumors.
Horm Metab Res.
2007;
39
461-466
29
Stratakis CA.
Adrenocortical tumors, primary pigmented adrenocortical disease(PPNAD)/Carney complex,
and other bilateral hyperplasias: the NIH studies.
Horm Metab Res.
2007;
39
467-473
30
Ehrhart-Bornstein M, Hilbers U.
Neuroendocrine properties of adrenocortical cells.
Horm Metab Res.
1998;
30
436-439
31
Toti P, Regoli M, Nesi G, Occhini R, Bartolommei S, Fonzi L, Bertelli E.
Nestin expression in normal adrenal gland and adrenocortical tumors.
Histol Histopathol.
2005;
20
1115-1120
32
Marx C, Wolkersdörfer GW, Brown JW, Scherbaum WA, Bornstein SR.
MHC class II expression – a new tool to asses dignity in adrenocortical tumors.
J Clin Endocrinol Metab.
1996;
81
4488-4491
Correspondence
H. S. WillenbergMD
Department of Endocrinology
Diabetes and Rheumatology
University Hospital Düsseldorf
Moorenstraße 5
40225 Düsseldorf
Germany
Phone: +49/211/811 78 10
Fax: +49/211/811 78 60
Email: Holger.Willenberg@uni-duesseldorf.de