Document Type : Original Article

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.

1. 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.
2. 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.
3. Zeisberg M, Neilson EG. Biomarkers for epithelialmesenchymal
transitions. J Clin Invest. 2009;119(6):
1429-37. doi: 10.1172/JCI36183.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.