Insulin-like growth factor II-messenger RNA-binding protein-3 and lung cancer
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.
SourceAvailable from: Valentina Vaira[Show abstract] [Hide abstract]
ABSTRACT: Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas.BioMed Research International 01/2015; 2015:413897. DOI:10.1155/2015/413897 · 2.71 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Introduction: We evaluated the expression of the oncofetal protein IMP3 in a series of neuroendocrine tumors of the lung, correlating our results with proliferating index Ki67 and with the expression of the two most studied stem cell markers in lung cancer, Nanog and Oct3/4. Methods: A total of 74 patients with a diagnosis of neuroendocrine tumor including 46 cases of typical carcinoid, nine cases of atypical carcinoids, 13 cases of large cell neuroendocrine carcinomas and six cases of small cell carcinomas were enrolled. Results: IMP3 was expressed in 50% of small cell carcinomas, 84% of large cell neuroendocrine carcinomas, 55% of atypical carcinoids and 10% of typical carcinoids. IMP3-positive cases showed significantly decreased overall and disease-free survival time compared with IMP3-negative cases. Nanog was expressed in 50% of small cell carcinomas, 31% of large cell neuroendocrine carcinomas, 33% of atypical carcinoids and 15% of typical carcinoids, and 68% of IMP3-positive tumors were also enriched for Nanog expression. Conversely, Oct3/4 expression could not be detected in all the analyzed series. When combining Ki67 and IMP3 expression we demonstrated that all the cases with a Ki67 index higher than 4% were also IMP3-positive, and their simultaneous expression was a poor prognostic factor. Conclusions: IMP3 is a marker of poor outcome in lung neuroendocrine tumors; its correlation with Nanog expression suggest an implication of IMP3 in stem cell processes and its association with a Ki67 labeling index higher than 4% stratifies a subset of atypical carcinoids with a higher risk of recurrence and mortality.Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2014; 9(11). DOI:10.1097/JTO.0000000000000316 · 4.55 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The utility of combination with CK5/6, IMP3 and TTF1 to differentiate among reactive mesothelial cells (RMs), metastatic adenocarcinoma of lung (LAC) and non-lung (NLAC) origin was investigated by using immunocytochemistry (ICC) and conventional PCR (C-PCR) in pleural effusion. A total of 108 cell blocks (32 RMs, 51 LAC and 25 NLAC were evaluated by ICC for CK5/6, IMP3 and TTF1 protein expression. In addition, we further performed C-PCR for amplification of CK5/6, IMP3 and TTF1 DNA from 28 specimens (9 MAC and 7 RMs, 6 LAC and 6 NLAC) for molecular diagnosis. CK5/6 staining was observed in the majority of reactive specimens (78.1%) and was rare in adenocarcinoma cells (14.5%), whereas the opposite was true for IMP3 and TTF1. We found a high frequency of TTF1 positivity (76.5%) in LAC, but not in NLAC (4.0%); while there was no significant difference of IMP3 expression in LAC (88.2%) and NLAC (88.0%). The 487 bp DNA fragments of IMP3 was expected to be amplified in 6/9 of adenocarcinoma cases showed negative in ICC; and the 394 bp DNA fragments of CK5/6 was also expected to be amplified in 4/7 of RMs cases showed negative in ICC. Consistent with ICC results, there was significant difference of TTF1 expression in the LAC and NLAC compared with IMP3 expression. The combination with CK5/6, IMP3 and TTF1 immunostaining appears to be useful to improve the accuracy of cytological diagnoses between RMs, metastatic adenocarcinoma of lung and non-lung origin in pleural effusion. In addition, C-PCR may act as a useful supplemental approach for ICC, especially negative cases in ICC for differential cytological diagnosis.