scholarly journals Immunohistochemical expression of stem cell markers in pheochromocytomas/paragangliomas is associated with SDHx mutations

2015 ◽  
Vol 173 (1) ◽  
pp. 43-52 ◽  
Author(s):  
L Oudijk ◽  
C M Neuhofer ◽  
U D Lichtenauer ◽  
T G Papathomas ◽  
E Korpershoek ◽  
...  

ObjectivePheochromocytomas (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.DesignWe 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.ResultsSOX2, 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.ConclusionImmunohistochemical 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.

2010 ◽  
Vol 79 (1) ◽  
pp. 1 ◽  
Author(s):  
Young Hee Choi ◽  
Min Gyu Kim ◽  
Dong-Hyun Ahn ◽  
Seong Jin Cho ◽  
Soo Hee Hong ◽  
...  

2014 ◽  
Vol 9 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Willam Sterlacci ◽  
Spasenija Savic ◽  
Michael Fiegl ◽  
Ellen Obermann ◽  
Alexandar Tzankov

2014 ◽  
Vol 34 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Mousa A. Shaheen ◽  
Nedal A. Hegazy ◽  
Ola H. Nada ◽  
Nehal A. Radwan ◽  
Suzan M. Talaat

2016 ◽  
Vol 212 (9) ◽  
pp. 825-832 ◽  
Author(s):  
Elia Guadagno ◽  
Giorgio Borrelli ◽  
Marialuisa Califano ◽  
Gaetano Calì ◽  
Domenico Solari ◽  
...  

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 333-333 ◽  
Author(s):  
Ravendra Ryan Moniz ◽  
Walter Henriques Costa ◽  
Victor Soares Fanni ◽  
Isabela Werneck Cunha ◽  
Rafael Malagoli Rocha ◽  
...  

333 Background: The purpose of this study was to examine the immunohistochemical expression of OCT3/4, CCND2, DPPA4 and NANOG in primary non-seminomatous germ cell testicular tumors that might be associated with different entities of germ cell tumors. OCT3/4, NANOG, DPPA4 and CCND2 have been identified as key regulators of pluripotency in mammalian embryonic and induced stem cells. Methods: Tissue samples of non seminoma testicular germ cell tumors including carcinoma in situ (CIS, n=10), seminoma component (n=5), embryonic carcinoma (n=20), mature teratoma (n= 7), immature teratoma (n=7), yolk sac tumor (n=5) and choriocarcinoma (n=3) were first analyzed by histological evaluation followed by selection of the appropriate tissue sections prepared from paraffin embedded testicular tissue blocks fixed with buffered formalin. To investigate immunohistochemical expression, of cancer stem cell markers samples tissues were analyzed under central pathological evaluation. Results: In CIS cells all markers were detected with a strong immunohistochemical expression suggesting that CIS cells maintain characteristics of embryonic stem cells. The invasive tumor samples, in comparison, showed a more heterogeneous expression pattern of OCT3/4, NANOG, DPPA4 and CCND2. There was an abundant expression in seminomas and embryonic carcinomas compared to a marked reduction expression in choriocarcinoma and teratomas. The expression of the markers was related to tumoral tissue differentiation. The seminomatous component and the embryonic carcinoma and undifferentiated tissues such as intratubular neoplasia presented elevated expressions. Specialized tissues such as teratoma and choriocarcinoma present low expression levels or absence of studied markers. The teratomatous subtypes do not express NANOG. The sub-type coriocarcinoma tumors do not express CCND2 and NANOG. Conclusions: The immunohistochemical expression of stem cell markers OCT3/4, NANOG, DPPA4 and CCND2 follow a specific pattern that is related to tumoral differentiation and consequent loss of pluripotency characteristics.


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