Investigation of GREMLIN 1, COL15A1 immunoreactivity and the relationship between microvessel density and GREMLIN 1 in papillary renal cell carcinoma and chromophobe renal cell carcinoma

Year 2016, Volume: 3 Issue: 4, 184 - 91, 15.04.2016

Sevgul Kara , Metin Karakok

https://doi.org/10.17546/msd.61375

Abstract

Objective: The current study aimed to investigate expressions of Gremlin 1 (GREM1) (a bone morphogenetic protein antagonist and a proangiogenic factor) and COL15A1 (Collagen type XV alpha-1, encodes the proteoglycans
located in various human tissues and particularly in the basement membrane) immunohistochemically in papillary renal cell carcinoma (PRCC) and chromophobe renal cell carcinoma (CRCC) in order to assess the relationship between these markers and said tumors and also explore associations of GREM1 with angiogenesis, tumor necrosis and tumor diameter by looking at the microvascular density (MVD) through the expression of COL15A1 in vascular endothelium.

Material and Method: GREM1 and COL15A1 expressions were investigated in 20 PRCC and 39 CRCC patients. Cytoplasmic staining with GREM1 and COL15A1 was examined. Microvascular structures stained with COL15A1 were examined in order to evaluate angiogenic profile.

Results: In CRCC, GREM1 staining was statistically significant in tumor tissues compared to intact tissues (p=0.006). The relationship between MVD and GREM1 staining was statistically significant in PRCC (p=0.007). Cytoplasmic staining with COL15A1 observed in PRCC was statistically significant (p=0.005).

Conclusion: Positive GREM1 staining observed in both tumor groups and much higher expression of this marker particularly in the tubular epithelium of the neighboring normal tissue supports our argument that this gene might be a tumor suppressor gene.

Keywords

Chromophobe renal cell carcinoma; papillary renal cell carcinoma; Gremlin 1; collagen type XV alpha-1; angiogenesis

References

• Iris J.H. van Vlodrop, Marcella M.L. Baldewijns, Kim M. Smits, Leo J. Schouten, et al. Prognostic significance of Gremlin 1 (GREM1) promoter CpG island hypermethylation in clear cell renal cell carcinoma. The American Journal of Pathology 2010; 176.
• Stabile H, Stefania Mitola S, Emanuela Moroni E, Mirella Belleri M, Nicoli S et al. Bone morphogenic protein antagonist Drm/Gremlin is a novel proangiogenic factor Blood, 2007;109:5:1833-1840.
• Amenta PS, Scivoletti NA, Newman MD, Sciancalepore JP, Li D et al. Proteoglycan-collagen XV in human tissues is seen linking banded collagen fibers subjacent to the basement membrane. J Histochem Cytochem 2005;53:165–76.
• Morris MR, Ricketts C, Gentle D, Abdulrahman M, Clarke N et al. Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma. Oncogene. 2010; 29(14):2104-17.
• Dr Kürşat Yıldız böbrek tümörlerinin patolojik sınıflamasında güncel gelişmeler. Üroonkoloji bülteni 2011;3: 86-90.
• Ellinger J, Holl D, Nuhn P, Kahl P, Haseke N et al. DNA hypermethylation In papillary renal cell carcinoma. BJUI international 2010;107:664-669.
• Chen MH, Yeh YC, Shyr YM, Jan YH, Chao Y et al. Expression of Gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumorsJournal of Gastroenterology. 2013;48:101-108.
• Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010; 127(12):2893-917.
• Pascual D and Borque A. Epidemiology of kidney cancer. Adv Urol. 2008; 782381.
• S. E. Mills, Strenberg’s Diagnostic Surgıcal Pathology, fifth edition, Wolters Kluwer, Lippincott Williams anda Wilkins 2010;1757-1798.
• Bora G. ve Yurter H. Epigenetic diseases and therapeutic approaches. Hacettepe Tıp Dergisi. 2007; 38:48-54.
• Mulvihill MS, Kwon Y, Lee S, Fang LT, Choi H et al. Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells. Plos one. 2012;7:8:1-8
• Sneddon JB, Zhen HH, Montogomery K, van de Rijn M, Twart AD et al. Bone morphogenetic protein antagonist Gremlin 1 is widely expressed by cancer- associated stromal cells and can promote tumor cell proliferation. Proceedings of the national academy of sciences. 2006;103:14842-14847.
• Wang DJ, Zhi XY, Zhang SC, Jiang M, Liu P, et al. The bone morphogenetic protein antagonist Gremlin is overexpressed in human malignant mesothelioma. 2011; doi 10.3892/or.2011.1463:58-64.
• Namkoong H, Shin SM, Kim HK, et al. The bone morphogenetic protein antagonist Gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein. BMC Cancer. 2006;6:74.