BIOMAT Database Logo BIOMAT Database Logo

Immunohistochemical expression of stem cell markers in pheochromocytomas/paragangliomas is associated with SDHx mutations. 2015

L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Department of PathologyErasmus MC Cancer Institute, University Medical Center Rotterdam, Postbus 2040, 3000 CA Rotterdam, The NetherlandsEndocrine Research UnitMedizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, D-80336 Munich, GermanyDepartment of Medical OncologyErasmus MC Cancer Institute, Cancer Genomics Netherlands, Rotterdam, The NetherlandsHuman Cancer Genetics ProgrammeSpanish National Cancer Research Centre (CNIO) and ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, SpainDepartment of Experimental and Clinical Biomedical SciencesUniversity of Florence and Istituto Toscano Tumori, Florence, ItalyAssistance Publique-Hôpitaux de ParisHôpital Européen Georges Pompidou, Service de Génétique, F-75015 Paris, FranceINSERMUMR970, Paris-Cardiovascular Research Center at HEGP, F-75015 Paris, FranceUniversité Paris DescartesFaculté de Médecine, F-75005 Paris, FranceDepartment of PathologyReinier de Graaf Hospital, Delft, The Netherlands.

OBJECTIVE Pheochromocytomas (PCCs) are neuroendocrine tumors that occur in the adrenal medulla, whereas paragangliomas (PGLs) arise from paraganglia in the head, neck, thorax, or abdomen. In a variety of tumors, cancer cells with stem cell-like properties seem to form the basis of tumor initiation because of their ability to self-renew and proliferate. Specifically targeting this small cell population may lay the foundation for more effective therapeutic approaches. In the present study, we intended to identify stem cells in PCCs/PGLs. METHODS We examined the immunohistochemical expression of 11 stem cell markers (SOX2, LIN28, NGFR, THY1, PREF1, SOX17, NESTIN, CD117, OCT3/4, NANOG, and CD133) on tissue microarrays containing 208 PCCs/PGLs with different genetic backgrounds from five European centers. RESULTS SOX2, LIN28, NGFR, and THY1 were expressed in more than 10% of tumors, and PREF1, SOX17, NESTIN, and CD117 were expressed in <10% of the samples. OCT3/4, NANOG, and CD133 were not detectable at all. Double staining for chromogranin A/SOX2 and S100/SOX2 demonstrated SOX2 immunopositivity in both tumor and adjacent sustentacular cells. The expression of SOX2, SOX17, NGFR, LIN28, PREF1, and THY1 was significantly associated with mutations in one of the succinate dehydrogenase (SDH) genes. In addition, NGFR expression was significantly correlated with metastatic disease. CONCLUSIONS Immunohistochemical expression of stem cell markers was found in a subset of PCCs/PGLs. Further studies are required to validate whether some stem cell-associated markers, such as SOX2, could serve as targets for therapeutic approaches and whether NGFR expression could be utilized as a predictor of malignancy.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010235 Paraganglioma A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion, such as the carotid body, or medulla of the adrenal gland (usually called a chromaffinoma or pheochromocytoma). It is more common in women than in men. (Stedman, 25th ed; from Segen, Dictionary of Modern Medicine, 1992) Paraganglioma, Gangliocytic,Paragangliomata,Gangliocytic Paraganglioma,Gangliocytic Paragangliomas,Paragangliomas,Paragangliomatas
D010673 Pheochromocytoma A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of EPINEPHRINE and NOREPINEPHRINE, is HYPERTENSION, which may be persistent or intermittent. During severe attacks, there may be HEADACHE; SWEATING, palpitation, apprehension, TREMOR; PALLOR or FLUSHING of the face, NAUSEA and VOMITING, pain in the CHEST and ABDOMEN, and paresthesias of the extremities. The incidence of malignancy is as low as 5% but the pathologic distinction between benign and malignant pheochromocytomas is not clear. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1298) Pheochromocytoma, Extra-Adrenal,Extra-Adrenal Pheochromocytoma,Extra-Adrenal Pheochromocytomas,Pheochromocytoma, Extra Adrenal,Pheochromocytomas,Pheochromocytomas, Extra-Adrenal
D005060 Europe The continent north of AFRICA, west of ASIA and east of the ATLANTIC OCEAN. Northern Europe,Southern Europe,Western Europe
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000310 Adrenal Gland Neoplasms Tumors or cancer of the ADRENAL GLANDS. Adrenal Cancer,Adrenal Gland Cancer,Adrenal Neoplasm,Cancer of the Adrenal Gland,Neoplasms, Adrenal Gland,Adrenal Cancers,Adrenal Gland Cancers,Adrenal Gland Neoplasm,Adrenal Neoplasms,Cancer, Adrenal,Cancer, Adrenal Gland,Cancers, Adrenal,Cancers, Adrenal Gland,Neoplasm, Adrenal,Neoplasm, Adrenal Gland,Neoplasms, Adrenal

Related Publications

L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
DIAGNOSIS of ENDOCRINE DISEASE: SDHx mutations: beyond pheochromocytomas and paragangliomas.
January 2018, European journal of endocrinology,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Metabolomic Urine Profile: Searching for New Biomarkers of SDHx-Associated Pheochromocytomas and Paragangliomas.
November 2019, The Journal of clinical endocrinology and metabolism,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Mediastinal paragangliomas related to SDHx gene mutations.
September 2016, Kardiochirurgia i torakochirurgia polska = Polish journal of cardio-thoracic surgery,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Molecular markers of paragangliomas/pheochromocytomas.
April 2017, Oncotarget,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
LncRNA expression and SDHB mutations in pheochromocytomas and paragangliomas.
December 2021, Annals of diagnostic pathology,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Expression of Contactin 4 Is Associated With Malignant Behavior in Pheochromocytomas and Paragangliomas.
January 2018, The Journal of clinical endocrinology and metabolism,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations.
November 2019, The Journal of clinical endocrinology and metabolism,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Familial pheochromocytomas and paragangliomas associated with mutations of the succinate dehydrogenase genes.
May 2007, Expert review of endocrinology & metabolism,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas.
January 2016, Cytogenetic and genome research,
L Oudijk, and C M Neuhofer, and U D Lichtenauer, and T G Papathomas, and E Korpershoek, and H Stoop, and J W Oosterhuis, and M Smid, and D F Restuccia, and M Robledo, and A A de Cubas, and M Mannelli, and A P Gimenez-Roqueplo, and W N M Dinjens, and F Beuschlein, and R R de Krijger
Malignant pheochromocytomas/paragangliomas harbor mutations in transport and cell adhesion genes.
May 2016, International journal of cancer,
Copied contents to your clipboard!