Indian Journal of Pathology and Microbiology

ORIGINAL ARTICLE
Year
: 2011  |  Volume : 54  |  Issue : 2  |  Page : 273--278

Expression of erythropoietin and its receptor increases in colonic neoplastic progression: The role of hypoxia in tumorigenesis


Zoltan Gombos1, Ludovit Danihel2, Vanda Repiska3, Geza Acs4, Emma Furth5 
1 Department of Pathology, Lafayette General Medical Center, Lafayette, LA, USA
2 Department of Pathology, Comenius University School of Medicine, Bratislava, Slovakia
3 Institute of Medical Biology and Genetics, Comenius University School of Medicine, Bratislava, Slovakia
4 Department of Anatomic Pathology and Women's Oncology, Moffitt Cancer Center, Tampa, FL, USA
5 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA

Correspondence Address:
Zoltan Gombos
Department of Pathology, Lafayette General Medical Center, 1214 Coolidge Blvd, Lafayette, LA 70503
USA

Background: Tissue hypoxia is a characteristic patho-physiologic property of colorectal cancer. This process may also add to a therapeutic problem of solid tumor resistance to chemo- and radiation therapy. Erythropoietin (Epo) expression is induced by tissue hypoxia. Acting via its receptor (EpoR), Epo inhibits apoptosis of erythroid cells and has been shown to rescue neurons from hypoxic damage. Increased Epo and EpoR expression has been recently described in human breast, renal and cervical carcinoma. Given the characteristic tumor diathesis present in majority of colorectal cancers, we examined whether Epo signaling may play a role in colonic neoplastic progression. Materials and Methods: Expression of Epo and EpoR was examined using immunohistochemistry in 24 cases of primary colorectal and metastatic adenocarcinomas versus adenomas and normal colonic mucosa. Immunohistochemical stains were evaluated semiquantitatively based on a four-tiered scale. Based on the combination of extent and intensity of immunoreactivity, an immunostaining score (0-300) was determined for each sample. Expression of Epo and EpoR protein and mRNA was examined using Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively, in both normal colonic tissue and carcinoma specimens in five cases. Results: Epo expression was sequentially increased in normal colonic mucosa (8.3 ± 5.6, mean ± SEM), adenoma (26.4 ± 9.1), primary carcinoma (96.1 ± 12.8) and metastatic carcinoma (122 ± 51.3). EpoR expression was also sequentially increased in normal colonic mucosa (22.3 ± 11.8), adenoma (108.7 ± 24.2), primary carcinoma (178.7 ± 16.6) and metastatic carcinoma (220 ± 58.3) (P< 0.05 for all results). Epo and EpoR showed enhanced expression in the areas adjacent to ischemia/necrosis. Western blot and RT-PCR analysis revealed increased EpoR protein and mRNA levels in carcinoma compared to normal mucosal colon specimens. Focal stromal Epo and EpoR immunoreactivity was present in 10 and 12 cases, respectively. Conclusions: The uniform increase in the expression of Epo and EpoR along the colonic neoplastic sequence and further increase in ischemic/necrotic areas indicates that the Epo signaling pathway is an important component in colon carcinogenesis including possible epithelial-stromal interactions.


How to cite this article:
Gombos Z, Danihel L, Repiska V, Acs G, Furth E. Expression of erythropoietin and its receptor increases in colonic neoplastic progression: The role of hypoxia in tumorigenesis.Indian J Pathol Microbiol 2011;54:273-278


How to cite this URL:
Gombos Z, Danihel L, Repiska V, Acs G, Furth E. Expression of erythropoietin and its receptor increases in colonic neoplastic progression: The role of hypoxia in tumorigenesis. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Sep 26 ];54:273-278
Available from: http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2011;volume=54;issue=2;spage=273;epage=278;aulast=Gombos;type=0