Insulin-like growth factor II-messenger RNA-binding protein-3 and lung cancer

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Biotechnic & Histochemistry (Impact Factor: 1). 08/2011; 87(1):24-9. DOI: 10.3109/10520295.2011.591831
Source: PubMed

ABSTRACT Insulin-like growth factor II-messenger RNA-binding protein 3 (IMP3) is an oncofetal RNA-binding protein that promotes tumor cell proliferation by enhancing IGF-II protein synthesis and inducing cell adhesion and invasion by stabilizing CD44 mRNA. IMP3 expression has been studied in many human neoplasms with growing evidence that IMP3 is a biomarker of enhanced tumor aggressiveness. IMP3 expression has been correlated with a poorer phenotypic profile including increased risk of metastases and decreased survival. Only a few studies have examined IMP3 expression in lung cancers. We review here the literature concerning IMP3 expression in lung neoplasms, specifically adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors of the lung. IMP3 immunohistochemical expression was reported in 27-55% of cases of primary pulmonary adenocarcinoma and in 75-90% of cases of squamous cell carcinoma of the lung. In adenocarcinoma, IMP3 expression was reported to be correlated with more poorly differentiated histological grade, advanced stage of disease and lymph node metastases. IMP3 expression also may be a marker of high grade pre-invasive squamous lesions including high grade dysplasia and carcinoma in situ. In neuroendocrine tumors of the lung, IMP3 expression was expressed in all reported cases of large cell neuroendocrine carcinoma and small cell lung carcinoma, but expression was limited in carcinoid tumors. Overall, IMP3 appears to be a useful diagnostic marker for lung cancer pathology including for discriminating high grade neuroendocrine tumors and low grade carcinoids and for identifying high grade pre-invasive squamous lesions.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Distinguishing malignant mesotheliomas from benign mesothelial proliferations on hematoxylin and eosin-stained sections can be extremely challenging. Various immunohistochemical stains have been suggested to help in making this distinction, but all are controversial. Recently, IMP3 (insulin-like growth factor II mRNA binding protein 3) and GLUT-1 (glucose transporter protein 1) have been proposed as immunohistochemical markers that are positive in mesotheliomas but not in benign proliferations. We evaluated the performance of these markers on a tissue microarray containing 30 malignant mesotheliomas and 48 benign thoracic or abdominal mesothelial proliferations. IMP3 was positive in 53% of malignant and 27% of benign cases (P=0.03), whereas GLUT-1 was positive in 60% of malignant and 13% of benign cases (P=0.0003). Forty-three percent of malignant cases, but only 4% of benign cases, were positive for both IMP3 and GLUT-1 (P=0.00003). We conclude that, statistically, both IMP3 and GLUT-1 are more frequently positive in malignant compared with benign mesothelial processes; however, the frequency of positive staining in benign cases is too high to allow their diagnostic use as single stains. The combination of both markers may be of greater diagnostic value, but this hypothesis should be confirmed in further studies.
    The American journal of surgical pathology 10/2012; 37(3). DOI:10.1097/PAS.0b013e31826ab1c0 · 4.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION: Insulin-like growth factor-II mRNA-binding protein 3 (IMP3), a newly identified oncofetal RNA-binding protein, plays a pivotal role in the regulation of cell growth and migration during early stages of embryogenesis, and is found to be expressed in various human cancers. In this study, we elucidated the clinicopathological significance of IMP3 expression in intrahepatic cholangiocarcinoma (ICC). METHODS: From March 1995 to December 2003, 61 surgically resected, unifocal primary ICCs were studied. IMP3 protein expression was detected by immunohistochemical staining. RESULTS: IMP3 protein was expressed in 25 of 61 ICCs (41.0%). In addition to correlating with tumor grade (p=0.0276), tumor stage (p=0.0059), lymphovascular invasion (p=0.0198), serum carbohydrate antigen 19-9 level (p=0.0146), IMP3 expression predicted early tumor recurrence (ETR) (p=0.0059) and was a strong indicator of worse disease-free survival (p=0.0001) and overall survival (p=0.0007). Even though we did not find that IMP3 expression exerted prognostic impact independent of tumor stage, multivariate analysis confirmed that IMP3 expression was an independent risk factor of high-stage tumor and ETR (p=0.0170, and p=0.0052, respectively), and thus it contributed to poor prognosis in ICC patients. CONCLUSIONS: IMP3 expression can serve as a novel maker for ETR and prognostic prediction, and may be a target for adjuvant therapy of patients with ICC after tumor resection.
    International Journal of Surgery (London, England) 12/2012; 11(1). DOI:10.1016/j.ijsu.2012.11.021 · 1.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To determine whether the oncofetal protein IMP3 is detectable in endometriomas with or without histological atypia and whether IMP3 staining can be used as a triage tool to identify foci of atypical endometriosis in doubtful cases. DESIGN: Retrospective study. SETTING: Academic department and referral center for endometriosis. PATIENT(S): A consecutive series of 516 women who underwent excision of 874 endometriomas. INTERVENTION(S): Histological review by three expert pathologists and immunohistochemical staining for IMP3. MAIN OUTCOME MEASURE(S): Test performance of IMP3 immunohistochemistry versus first-round histology. RESULT(S): The prevalence of atypical endometriosis was 1.7% (95% confidence interval [CI], 0.9%-3.3%) based on the number of women and 1.0% (95% CI, 0.5%-1.9%) based on the number of cysts. Three cases of atypical endometriosis were identified at first-round histological examination. Immunohistochemistry detected seven of the eight cases diagnosed as preneoplastic atypia at second-round histology and one case diagnosed as reactive atypia at second-round histology. The sensitivity of first-round histology was 33.3%, compared with 88.9% of IMP3 immunohistochemistry. CONCLUSION(S): Immunohistochemical staining for IMP3 expression is a simple, inexpensive, and sensitive test that can be used in routine clinical practice as a triage tool to discriminate between cytological/structural atypia and confounding benign conditions.
    Fertility and sterility 03/2013; 99(7). DOI:10.1016/j.fertnstert.2013.02.002 · 4.59 Impact Factor
Show more