Imp3 Expression in Benign and Malignant Thyroid Tumors and Hyperplastic Nodules

Abstract

Background: IMP3, a member of insulin-like growth factor II m RNA binding protein family, seems to be promising in the diagnosis of carcinomas of many organs as well as malignant melanomas and some sarcomas. It is postulated that it might be a marker of malignancy. The results of the few prior studies indicate that IMP3 has the potential to be useful in distinguishing benign and malignant tumors of thyroid. Aims: We aimed to evaluate the immunohistochemical expression of IMP3 in non-neoplastic nodules and benign and malignant tumors of the thyroid. Study Design: Diagnostic accuracy study. Methods: Overall, 92 thyroid lesions, including 22 nodular hyperplasia (NH), 14 follicular adenoma (FA), 9 follicular carcinoma (FC), 37 papillary carcinoma (PC) (15 follicular variant), 3 well differentiated carcinoma-not otherwise specified (WDC-NOS), 4 poorly differentiated carcinoma (PDC) and anaplastic carcinoma (AC) were included. Immunohistochemically, cytoplasmic expression of IMP3 was evaluated in terms of extent and intensity of the staining semi-quantitatively and an immunohistochemical score (IHS) was obtained for each case. A score higher than 2 was considered positive staining. Results: In contrast with previous studies, we observed positive staining in benign lesions, especially in benign tumors. For identifying malignant tumors, the sensitivity of IMP3 was 82.1%, specificity was 33.3%, positive predictive value (PPV) was 65.7% and negative predictive value (NPV) was 54.5%. In distinguishing neoplastic and hyperplastic lesions, the sensitivity was 50%, specificity was 15.7%, PPV was 15.7% and NPV was 50%. The IMP3 expression was similar for FA and well differentiated carcinomas (p=0.434), but there was a significant difference between hyperplastic nodules and FA (p=0.011). Conclusion: Our data suggest that IMP3 is effective in discriminating hyperplastic and neoplastic lesions but not useful in differentiating benign tumors from malignant tumors.

Keywords

• Immunohistochemistry, IMP3, thyroid, tumor

Kaynakça

1. 1. de Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpção LV, Metze K, Ward LS. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 2005;47:391-401. [CrossRef]
2. 2. Scognamiglio T, Hyjek E, Kao J, Chen YT. Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol 2006;126:700-8. [CrossRef]
3. 3. de Matos LL, Del Giglio AB, Matsubayashi CO, de Lima Farah M, Del Giglio A, da Silva Pinhal MA. Expression of CK-19, galectin-3 and HBME-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagn Pathol 2012;7:97. [CrossRef]
4. 4. Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Matsuzuka F, et al. Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma. Pathology 2005;37:296-8. [CrossRef]
5. 5. Mehrotra P, Okpokam A, Bouhaidar R, Johnson SJ, Wilson JA, Davies BR, et al. Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms. Histopathology 2004;45:493-500. [CrossRef]
6. 6. Sahoo S, Hoda SA, Rosai J, DeLellis RA. Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma: a note of caution. Am J Clin Pathol 2001;116:696-702. [CrossRef]
7. 7. Slosar M, Vohra P, Prasad M, Fischer A, Quinlan R, Khan A, et al. Insulin-like growth factor mRNA Binding protein 3 (IMP3) is differentially expressed in benign and malignant follicular patterned thyroid tumors. Endocr Pathol 2009;20:149-57. [CrossRef]
8. 8. Jin L, Seys AR, Zhang S, Erickson-Johnson MR, Roth CW, Evers BR, et al. Diagnostic utility of IMP3 expression in thyroid neoplasms. A quantitative RT-PCR study. Diag Mol Pathol 2009;19:63-9. [CrossRef]

9. 9. Asioli S, Erickson LA, Righi A, Jin L, Volante M, Jenkins S, et al. Poorly differentiated carcinoma of the thyroid: validation of the Turin proposal and analysis of IMP3 expression. Mod Pathol 2010;23:1269-78. [CrossRef]
10. 10. Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol 1999;19:1262-70.
11. 11. Nielsen FC, Nielsen J, Christiansen J. A family of IGF-II mRNA binding proteins (IMP) involved in RNA trafficking. Scand J Clin Lab Invest Suppl 2001;234:93-9. [CrossRef]
12. 12. Mueller-Pillasch F, Pohl B, Wilda M, Lacher U, Beil M, Wallrapp C, et al. Expression of the highly conserved RNA binding protein KOC in embryogenesis. Mech Dev 1999;88:95-9. [CrossRef]
13. 13. 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;7:556-64. [CrossRef]
14. 14. Jeng YM, Chang CC, Hu FC, Chou HY, Kao HL, Wang TH, et al. RNA-binding protein insulin-like growth factor II mRNAbinding protein 3 expression promotes tumor invasion and predicts early recurrence and poor prognosis in hepatocellular carcinoma. Hepatology 2008;48:1118-27. [CrossRef]
15. 15. Li C, Zota V, Woda BA, Rock KL, Fraire AE, Jiang Z, et al. Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations. Mod Pathol 2007;20:1263-8. [CrossRef]
16. 16. Li C, Rock KL, Woda BA, Jiang Z, Fraire AE, Dresser K, et al. IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16 (INK4a) expression. Mod Pathol 2007;20:242-7. [CrossRef]
17. 17. Kobel M, Xu H, Bourne PA, Spaulding BO, Shih IeM, Mao TL, et al. IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype. Mod Pathol 2009;22:469-75. [CrossRef]
18. 18. Samanta S, Sharma VM, Khan A, Mercurio AM. Regulation of IMP3 by EGFR signaling and repression by ERβ: implications for triple-negative breast cancer. Oncogene 2012;31:4689-97. [CrossRef]
19. 19. Sidoni A, Cartaginese F. IMP3 expression in triple-negative breast carcinoma. Hum Pathol 2010;41:1355-6. [CrossRef]
20. 20. Yantiss RK, Woda BA, Fanger GR, Kalos M, Whalen GF, Tada H, et al. KOC (K homology domain containing protein overexpression in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas. Am J Surg Pathol 2005;29:188-195. [CrossRef]
21. 21. Wang L, Li HG, Xia ZS, Lü J, Peng TS. IMP3 is a novel biomarker to predict metastasis and prognosis of gastric adenocarcinoma: a retrospective study. Chin Med J (Engl) 2010;123:3554-8.
22. 22. Li D, Yan D, Tang H, Zhou C, Fan J, Li S, et al. IMP3 is a novel prognostic marker that correlates with colon cancer progression and pathogenesis. Ann Surg Oncol 2009;16:3499-506. [CrossRef]
23. 23. Sitnikova L, Mendese G, Liu Q, Woda BA, Lu D, Dresser K, et al. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder. Clin Cancer Res 2008;14:1701-6. [CrossRef]
24. 24. Beljan Perak R, Durdov MG, Capkun V, Ivcevic V, Pavlovic A, Soljic V, et al. IMP3 can predict aggressive behaviour of lung adenocarcinoma. Diagn Pathol 2012;7:165. [CrossRef]
25. 25. Xu H. IMP3: a diagnostic and prognostic biomarker in malignant melanoma. Expert Rev Mol Diagn 2008;8:557-8. [CrossRef]
26. 26. Do SI, Kim YW, Park HR, Park YK. Expression of insulin-like growth factor-II mRNA binding protein 3 (IMP3) in osteosarcoma. Oncol Res 2008;17:269-72. [CrossRef]
27. 27. Cornejo K, Shi M, Jiang Z. Oncofetal protein IMP3: a useful diagnostic biomarker for leiomyosarcoma. Hum Pathol 2012;43:1567-72. [CrossRef]
28. 28. Liao B, Hu Y, Herrick DJ, Brewer G. The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells. J Biol Chem 2005;280:18517-24. [CrossRef]
29. 29. Mueller F, Bommer M, Lacher U, Ruhland C, Stagge V, Adler G,et al. KOC is a novel molecular indicator of malignancy. Br J Cancer 2003;88:699-701. [CrossRef]
30. 30. Kapoor S. IMP3: a new and important biomarker of systemic malignancies. Clin Cancer Res 2008;14:5640. [CrossRef