Differential Expression of MicroRNA-675, MicroRNA-139-3p and MicroRNA-335 in Benign and Malignant Adrenocortical Tumours

Overview

Journal J Clin Pathol

Specialty Pathology

Date 2011 Apr 8

PMID 21471143

Citations 59

Authors

K J Schmitz

J Helwig

S Bertram

S Y Sheu

A C Suttorp

J Seggewiss

E Willscher

M K Walz

K Worm

K W Schmid

Affiliations

Soon will be listed here.

Abstract

Background: For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours.

Methods: In order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16).

Results: Concerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist.

Conclusion: miRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential.

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References

Aiba M, Fujibayashi M . Histopathological diagnosis and prognostic factors in adrenocortical carcinoma. Endocr Pathol. 2005; 16(1):13-22. DOI: 10.1385/ep:16:1:013. View

Weiss L, Medeiros L, VICKERY JR A . Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989; 13(3):202-6. DOI: 10.1097/00000478-198903000-00004. View

Maragkakis M, Reczko M, Simossis V, Alexiou P, Papadopoulos G, Dalamagas T . DIANA-microT web server: elucidating microRNA functions through target prediction. Nucleic Acids Res. 2009; 37(Web Server issue):W273-6. PMC: 2703977. DOI: 10.1093/nar/gkp292. View

Soon P, Tacon L, Gill A, Bambach C, Sywak M, Campbell P . miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis in Adrenocortical Cancer. Clin Cancer Res. 2009; 15(24):7684-7692. DOI: 10.1158/1078-0432.CCR-09-1587. View

Giordano T, Kuick R, Else T, Gauger P, Vinco M, Bauersfeld J . Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res. 2009; 15(2):668-76. PMC: 2629378. DOI: 10.1158/1078-0432.CCR-08-1067. View

Schwertheim S, Sheu S, Worm K, Grabellus F, Schmid K . Analysis of deregulated miRNAs is helpful to distinguish poorly differentiated thyroid carcinoma from papillary thyroid carcinoma. Horm Metab Res. 2009; 41(6):475-81. DOI: 10.1055/s-0029-1215593. View

Schetter A, Leung S, Sohn J, Zanetti K, Bowman E, Yanaihara N . MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008; 299(4):425-36. PMC: 2614237. DOI: 10.1001/jama.299.4.425. View

Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri M, Troncone G . MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 2006; 13(2):497-508. DOI: 10.1677/erc.1.01209. View

van Slooten H, SCHABERG A, Smeenk D, MOOLENAAR A . Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer. 1985; 55(4):766-73. DOI: 10.1002/1097-0142(19850215)55:4<766::aid-cncr2820550414>3.0.co;2-7. View

10.

Vandenboom Ii T, Li Y, Philip P, Sarkar F . MicroRNA and Cancer: Tiny Molecules with Major Implications. Curr Genomics. 2009; 9(2):97-109. PMC: 2674802. DOI: 10.2174/138920208784139555. View

11.

Pallante P, Visone R, Croce C, Fusco A . Deregulation of microRNA expression in follicular-cell-derived human thyroid carcinomas. Endocr Relat Cancer. 2009; 17(1):F91-104. DOI: 10.1677/ERC-09-0217. View

12.

Zhang X, Chen J, Radcliffe T, Lebrun D, Tron V, Feilotter H . An array-based analysis of microRNA expression comparing matched frozen and formalin-fixed paraffin-embedded human tissue samples. J Mol Diagn. 2008; 10(6):513-9. PMC: 2570634. DOI: 10.2353/jmoldx.2008.080077. View

13.

Giordano T . Molecular pathology of adrenal cortical tumors: separating adenomas from carcinomas. Endocr Pathol. 2007; 17(4):355-63. DOI: 10.1007/s12022-006-0007-z. View

14.

Nikiforova M, Tseng G, Steward D, Diorio D, Nikiforov Y . MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008; 93(5):1600-8. PMC: 2386678. DOI: 10.1210/jc.2007-2696. View

15.

Lee R, Feinbaum R, Ambros V . The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75(5):843-54. DOI: 10.1016/0092-8674(93)90529-y. View

16.

Schmittgen T, Livak K . Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3(6):1101-8. DOI: 10.1038/nprot.2008.73. View

17.

Wightman B, Ha I, Ruvkun G . Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993; 75(5):855-62. DOI: 10.1016/0092-8674(93)90530-4. View

18.

Porkka K, Pfeiffer M, Waltering K, Vessella R, Tammela T, Visakorpi T . MicroRNA expression profiling in prostate cancer. Cancer Res. 2007; 67(13):6130-5. DOI: 10.1158/0008-5472.CAN-07-0533. View

19.

Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N . Widespread changes in protein synthesis induced by microRNAs. Nature. 2008; 455(7209):58-63. DOI: 10.1038/nature07228. View

20.

Sheu S, Grabellus F, Schwertheim S, Worm K, Broecker-Preuss M, Schmid K . Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours. Br J Cancer. 2009; 102(2):376-82. PMC: 2816660. DOI: 10.1038/sj.bjc.6605493. View