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.

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

“…However, as the number of studies suggesting biological and clinical relevance of IMP3 is rapidly increasing, there are also a growing number of reports revealing considerable discrepancies with respect to the frequency of expression in various types of cancer. For example, reported frequencies in IMP3 expression ranges from 0 to 83% in prostate cancer ( 13 – 16 ), from 11 to 86% in papillary thyroid cancer ( 17 – 20 ), from 11 to 65% in papillary renal cell cancer ( 9 , 12 ), from 0 to 52% in leiomyoma ( 21 , 22 ), from 21 to 71% in invasive urinary bladder tumor ( 23 , 24 ), from 50 to 100% in small cell lung cancer ( 3 , 25 ), and from 37 to 83% in malignant mesothelioma ( 26 , 27 ). Such discrepancies may be due to the use of different antibodies, staining protocols, and scoring criteria in these studies.…”

IMMUNOHISTOCHEMICAL VALIDATION OF INSULIN-LIKE GROWTH FACTOR II mRNA-BINDING PROTEIN 3 (IMP3) AS A DIAGNOSTIC MARKER IN SALIVARY GLAND TUMORS

“…This may be explained by the few types of tumors involved in their study and not including high grade tumors. Similarly, Kulaçoğlu and Erkılınç (13) found no significant difference in IMP3 expression between benign and malignant thyroid tumors. This may be attributed to variations in technical work or the clones of the antibodies used in different studies.…”

“…IMP3 expression has been detected in diverse malignant tumors and its immense expression has been correlated with poor prognosis and developing metastases (11). IMP3 expression has been reported in various malignant neoplasms including oral cancer (8), prostate cancer (12), thyroid cancer (13), lung cancer (14,15), esophageal cancer (16), colorectal cancer (17), bile duct cancer (18), cervical cancer (19), ovarian cancer (20), renal cancer (21) ,and bladder cancer (22).…”

Overview of established and emerging immunohistochemical biomarkers and their role in correlative studies in MRI

“…Insulin‐like growth factor 2 mRNA binding protein 3 (IMP3) is an oncofetal RNA binding protein that attaches to the 5′ untranslated region of the IGF‐II leader 3 mRNA that contains several K homology domains that are important in RNA binding, trafficking, stabilization, cell growth, and cell migration during the early stages of embryogenesis . It has been found to be re‐expressed in aggressive carcinomas including those of the pancreas, thyroid, and cervix . Enhanced IMP3 expression in the progression of renal cell carcinoma (RCC) is reported to cause cell migration and invasion through activation of the nuclear factor kappa B (NF‐κB) signaling pathway .…”