Document Type : Original Article(s)
Authors
Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
Abstract
Background: Renal cell carcinoma (RCC) is the most prevalent malignancy of kidney. Snail is a zinc-finger transcription factor, associated with advanced tumor stage and poor prognosis of RCC. Insulin-like mRNA-binding protein3 (IMP3) immunopositivity predicts metastatic progression and patients’ survival in RCC. Aldehyde dehydrogenase 1 (ALDH1) is a stem cell marker, expressed in many different solid tumors of bladder, pancreas, colon, and kidney. The present study aimed to assess the diagnostic value of Snail, IMP3, and ALDH1 expression in clear cell, papillary, and chromophobe variants of RCC.
Method: This retrospective study included 50 tissue blocks of RCC cases (35 clear cells, along with 11 papillary and four chromphobe carcinomas). Immunohistochemical staining was evaluated using antibody against Snail, IMP3, and ALDH1 in all the cases.
Results: Snail was observed to be 74.3% in clear cell RCC and 18.2% in papillary, but negatively expressed in all chromophobe carcinomas. IMP3 was expressed in 72.7% of papillary carcinomas and 28.6% of clear cell RCC; it was totally expressed in all chromophobe carcinomas. ALDH1 was expressed in 94.2% of clear cell RCC, 54.6% of papillary carcinomas, and 50% of chromophobe carcinomas. Snail, IMP3, and ALDH1 were found to be associated with advanced tumor stage and high grade; accordingly, they could be considered as poor markers for RCC patients.
Conclusion: ALDH1 is a good sensitive marker for diagnosis of RCC, especially for clear cell type, while IMP3 is a good marker for diagnosis of chromophobe carcinoma and Snail can be used for diagnosis of clear cell carcinoma.
Keywords
How to cite this article:
Atwa HA, Elaidy NF. Expression of snail, insulin-like mRNAbinding protein3 and aldehyde dehydrogenase 1 as diagnostic markers in clear cell, papillary and chromophobe variants of renal cell carcinoma. Middle East J Cancer. 2022;13(2):266- 74. doi: 10.30476/mejc.2021. 87231.1402.
- Rueckert J, Devitt K, Gardner JA. Renal cell carcinoma with monosomy 8: A case series and review of the literature. J Assoc Genet Technol. 2018;44(1):5-9.
- Muglia VF, Prando A. Renal cell carcinoma: histological classification and correlation with imaging findings. Radiol Bras. 2015;48(3):166-74. doi:10.1590/0100-3984.2013.1927.
- Zeisberg M, Neilson EG. Biomarkers for epithelialmesenchymal transitions. J Clin Invest. 2009;119(6):1429-37. doi: 10.1172/JCI36183.
- Andreiana BC, Stepan AE, Mărgăritescu C, Tăisescu O, Osman A, Simionescu C. Snail and e-cadherin immunoexpression in clear cell renal cell carcinoma. Curr Health Sci J. 2019;45(2):185-9. doi: 10.12865/CHSJ.45.02.09.
- Mikami S, Katsube K, Oya M, Ishida M, Kosaka T, Mizuno R, et al. Expression of Snail and Slug in renal cell carcinoma: E-cadherin repressor Snail is associated with cancer invasion and prognosis. Lab Invest. 2011;91(10):1443-58. doi:10.1038/labinvest.2011.111.
- Szarvas T, Tschirdewahn S, Niedworok C, Kramer G, Sevcenco S, Reis H, et al. Prognostic value of tissue and circulating levels of IMP3 in prostate cancer. Int J Cancer. 2014;135(7):1596-604. doi: 10.1002/ijc.28808.
- Ohashi R, Sangen M, Namimatsu S, Takei H, Naito Z. IMP3 contributes to poor prognosis of patients with metaplastic breast carcinoma: A clinicopathological study. Ann Diagn Pathol. 2017;31:30-5. doi:10.1016/j.anndiagpath.2017.05.015.
- Yan J, Wei Q, Jian W, Qiu B, Wen J, Liu J, et al. IMP3 predicts invasion and prognosis in human lung adenocarcinoma. Lung. 2016;194(1):137-46. doi:10.1007/s00408-015-9829-0.
- Yang F, Zhou Q, Meng L, Xing N. IMP3 is a biomarker for non-muscle-invasive urothelial carcinoma of the bladder associated with an aggressive phenotype. Medicine (Baltimore). 2019;98(27):e16009. doi:10.1097/MD.0000000000016009.
- Burdelski C, Jakani-Karimi N, Jacobsen F, Möller-Koop C, Minner S, Simon R, et al. IMP3 overexpression occurs in various important cancer types and is linked to aggressive tumor features: A tissue microarray study on 8,877 human cancers and normal tissues. Oncol Rep. 2018;39(1):3-12. doi:10.3892/or.2017.6072.
- Tschirdewahn S, Panic A, Püllen L, Harke NN, Hadaschik B, Riesz P, et al. Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma. Int J Cancer. 2019;145(2):531-9. doi:10.1002/ijc.32124.
- Marcato P, Dean CA, Giacomantonio CA, Lee PW. Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform. Cell Cycle. 2011;10(9):1378-84. doi: 10.4161/cc.10.9.15486.
- Su Y, Qiu Q, Zhang X, Jiang Z, Leng Q, Liu Z, et al. Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumor-initiating cells and associated with progression of bladder cancer. Cancer Epidemiol Biomarkers Prev. 2010;19: 327-37.
- Kahlert C, Bergmann F, Beck J, Welsch T, Mogler C, Herpel E, et al. Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer. BMC Cancer. 2011;11:275. doi: 10.1186/1471-2407-11-275.
- Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer. 2010;103(3):382-90. doi: 10.1038/sj.bjc.6605762.
- Bussolati B, Dekel B, Azzarone B, Camussi G. Human renal cancer stem cells. Cancer Lett. 2013;338(1):141-6. doi: 10.1016/j.canlet.2012.05.007.
- Wang K, Chen X, Zhan Y, Jiang W, Liu X, Wang X, et al. Increased expression of ALDH1A1 protein is associated with poor prognosis in clear cell renal cell carcinoma. Med Oncol. 2013;30(2):574. doi:10.1007/s12032-013-0574-z.
- Kaufhold S, Bonavida B. Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention. J Exp Clin Cancer Res. 2014;33(1):62. doi: 10.1186/s13046-014-0062-0.
- Cai J. Roles of transcriptional factor Snail and adhesion factor E-cadherin in clear cell renal cell carcinoma. Exp Ther Med. 2013;6(6):1489-93. doi: 10.3892/etm.2013.1345.
- Messai Y, Noman MZ, Derouiche A, Kourda N, Akalay I, Hasmim M, et al. Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression:relationship with Snail. Int J Oncol. 2010;36(5):1145-54. doi: 10.3892/ijo_00000597.
- Mikami S, Katsube K, Oya M, Ishida M, Kosaka T, Mizuno R, et al. Expression of Snail and Slug in renal cell carcinoma: E-cadherin repressor Snail is associated with cancer invasion and prognosis. Lab Invest. 2011;91(10):1443-58. doi:10.1038/labinvest.2011.111.
- Liu W, Liu Y, Liu H, Zhang W, An H, Xu J. Snail predicts recurrence and survival of patients with localized clear cell renal cell carcinoma after surgical resection. Urol Oncol. 2015;33(2):69. e1-10. doi:10.1016/j.urolonc.2014.08.003.
- Eronat O, Kandemir O, Onursever A. The expression level of vascular endothelial growth factor receptor-2, vascular endothelial growth factor receptor-3, and insulin-like growth factor II mRNA binding protein 3 in renal cell carcinoma: Can these markers indicate poor prognosis in immunohistochemical examination? Clin Cancer Investig J. 2018;7: 14-22. doi: 10.4103/ccij.ccij_84_17.
- Jiang Z, Chu PG, Woda BA, Rock KL, Liu Q, Hsieh CC, et al. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol. 2006;7(7):556-64. doi: 10.1016/S1470-2045(06)70732-X.
- Hoffmann NE, Sheinin Y, Lohse CM, Parker AS, Leibovich BC, Jiang Z, et al. External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma. Cancer. 2008;112(7):1471-9. doi: 10.1002/cncr.23296.
- Jiang Z, Lohse CM, Chu PG, Wu CL, Woda BA, Rock KL, et al. Oncofetal protein IMP3: a novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinomas. Cancer. 2008;112(12):2676-82. doi: 10.1002/cncr.23484.
- Pei X, Li M, Zhan J, Yu Y, Wei X, Guan L, et al. Enhanced IMP3 expression activates NF-κB pathway and promotes renal cell carcinoma progression. PLoS One. 2015;10(4): e0124338. doi: 10.1371/journal.pone.0124338.
- Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev Rep. 2011;7(2):292-306. doi: 10.1007/s12015-010-9208-4.
- Ozbek E, Calik G, Otunctemur A, Aliskan T, Cakir S, Dursun M, et al. Stem cell markers aldehyde dehydrogenase type 1 and nestin expressions in renal cell cancer. Arch Ital UrolAndrol. 2012;84(1):7-11.
- Ueda K, Ogasawara S, Akiba J, Nakayama M, Todoroki K, Ueda K, et al. Aldehyde dehydrogenase 1 identifies cells with cancer stem cell-like properties in a human renal cell carcinoma cell line. PLoS One. 2013;8(10):e75463. doi:10.1371/journal.pone.0075463.
- Ozbek E, Calik G, Otunctemur A, Aliskan T, Cakir S, Dursun M, et al. Stem cell markers aldehyde dehydrogenase type 1 and nestin expressions in renal cell cancer. Arch Ital UrolAndrol. 2012;84(1):7-11.
)