IMP3 can predict aggressive behaviour of lung adenocarcinoma.

Diagnostic Pathology (Impact Factor: 2.41). 11/2012; 7(1):165. DOI: 10.1186/1746-1596-7-165
Source: PubMed

ABSTRACT BACKGROUND: Lung cancer most often presents as an inoperable tumour and the diagnosis is usually performed on a small biopsy/cytology specimen. In the group of non small cell lung cancer - not otherwise specified, adenocarcinoma phenotype can be determined immunohistochemically using TTF-1 and Napsin A. Expression of oncofetal protein IMP3 in human cancer is associated with poor differentiation and aggressive behaviour. In the present study expression of IMP3 was correlated with expression of TTF-1 and Napsin A, histological subtype and clinical stage of lung adenocarcinoma. We were interested whether distant metastases are associated with IMP3 overexpression, regardless of the histologic subtype of adenocarcinoma. METHODS: In retrospective study, consecutive series of 105 patients with advanced lung adenocarcinoma diagnosed from 2006 to 2009 in Clinical Hospital Center Split, Croatia, were analysed. Clinical data were collected from the Pulmology Department and time of death from the Mortality Registry. Paraffin blocks of bronchoscopic biopsies were collected from the Institute of Pathology and 15 cases excluded from the analysis due to insufficient material. Expression of IMP3, Napsin A and TTF-1 were analysed by indirect enzyme immunohistochemistry. Statistical analysis was performed and P values less than 0.05 considered significant. RESULTS: Of 90 patients, 71 (78%) were males and 19 (22%) females. Median age for males was 61.5 years (min-max 43-83) and for females 61 years (min-max 44-86). Pleural effusion was found in 15 (16.6%) and distant metastases in 45 (50%) cases. According to histological subtypes, there were 34 acinar, 2 lepidic, 2 papillary and 52 solid subtypes. IMP3 overexpression was found in 63 cases (70%) and was correlated with solid subtype (P = 0.002) and negative/weak Napsin A expression (P = 0.004). Strong Napsin A expression correlated with TTF-1 expression (P = 0.003) and lower histological grades (P = 0.031). Patients with IMP3 overexpression more often had distant metastases than patients with negative IMP3, 55.5% versus 33.3% (P = 0.033). Non solid subtypes with IMP3 overexpression developed distant metastasis more common than non solid subtypes with negative IMP3, 72% versus 35% (P = 0.028). CONCLUSIONS: Expression of IMP3 correlates with solid subtype and with distant metastases regardless of histological subtype of lung adenocarcinoma. Virtual slides

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    • "RESULTS IMP3 and HMGA2 mRNA Are Coexpressed in Human Cancers High levels of RNA-binding IMP3 have been associated with poor outcome and metastasis in cancers of the lung, kidney, colorectal, breast, and ovary (Beljan Perak et al., 2012; Bellezza et al., 2009; Findeis-Hosey et al., 2010; Hoffmann et al., 2008; Jiang et al., 2008a, 2008b; Kö bel et al., 2009; Lochhead et al., 2012; Walter et al., 2009; Yuan et al., 2009). To identify putative oncogenic mechanisms connected to IMP3, we examined IMP3 mRNA expression in a series of 270 tumors from the above cancers and searched for transcripts that were correlated with the presence of IMP3. "
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    ABSTRACT: The IMP3 RNA-binding protein is associated with metastasis and poor outcome in human cancer. Using solid cancer transcriptome data, we found that IMP3 correlates with HMGA2 mRNA expression. Cytoplasmic IMP3 granules contain HMGA2, and IMP3 dose-dependently increases HMGA2 mRNA. HMGA2 is regulated by let-7, and let-7 antagomiRs make HMGA2 refractory to IMP3. Removal of let-7 target sites eliminates IMP3-dependent stabilization, and IMP3-containing bodies are depleted of Ago1-4 and miRNAs. The relationship between Hmga2 mRNA and IMPs also exists in the developing limb bud, where IMP1-deficient embryos show dose-dependent Hmga2 mRNA downregulation. Finally, IMP3 ribonucleoproteins (RNPs) contain other let-7 target mRNAs, including LIN28B, and a global gene set enrichment analysis demonstrates that miRNA-regulated transcripts in general are upregulated following IMP3 induction. We conclude that IMP3 RNPs may function as cytoplasmic safe houses and prevent miRNA-directed mRNA decay of oncogenes during tumor progression.
    Cell Reports 04/2014; 7(2). DOI:10.1016/j.celrep.2014.03.015 · 8.36 Impact Factor
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    ABSTRACT: BACKGROUND: Epithelial-mesenchymal transition (EMT) is defined as switc hing of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate that whether EMT-related proteins alterations are associated with clinicopathological features and prognosis in lung adenocarcinoma. METHODS: The expression of EMT-related proteins including cytokeratin, E-cadherin, TTF-1, beta-catenin, vimentin, Snail, Twist, CD44 was evaluated by immunohistochemistry using a tissue array method in the lung adenocarcinoma tissues of 95 patients. In addition, clinicopathological characteristics and survival were compared with the expression of EMT-related proteins. RESULTS: Loss of epithelial proteins and/or acquisition of the expression of mesenchymal proteins were observed in lung adenocarcinoma. These proteins' alteration was ass ociated with poor cell differentiation and poor patients' outcome, respectively. Subjects were divided into two groups according to the number of EMT-related proteins' alteration. A higher number of EMT-related proteins' alteration was found to be significantly as sociated with unfavorable outcome. Multivariate analysis showed that a higher number of EMT-related proteins' alteration was independently associated with poor prognosis. CONCLUSIONS: The number of EMT-related proteins' alteration is a significant prognostic marker to predict overall survival in patients with lung adenocarcinoma. The information generated will be valuable for the prognosis of patients with lung adenocarcinoma. Virtual slides The virtual slides for this article can be found here:
    Diagnostic Pathology 05/2013; 8(1):89. DOI:10.1186/1746-1596-8-89 · 2.41 Impact Factor
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    ABSTRACT: There are 2 types of bronchiolo-alveolar hyperplasia found in rat lungs. One is 'inflammatory hyperplasia' with a potential to recover in future with removal of the stimulating insult and the other is 'latent tumorigenic hyperplasia' as an independent preneoplastic lesion for adenocarcinoma. In the present experiment, we focused on rat lung bronchiolo-alveolar hyperplasia induced by 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which decreases with time after induction and reverts to normal, or by N-bis(2-hydroxypropyl)nitrosamine (DHPN), with tumorigenic potential to progress to adenoma and adenocarcinoma. Though NNK is a typical carcinogen inducing lung adenocarcinoma in female A/J mice, the tumorigenic potential by NNK in rats is weak. Differences between hyperplasias induced by DHPN and by NNK were here examined immunohistochemically. Formalin fixed paraffin embedded lung samples with hyperplastic and inflammatory lesions were obtained from rats exposed to DHPN or NNK and from lung inflammation models induced with fine particles like CuO, NiO and quartz. The 19 markers were examined immunohistochemically. Napsin A, in the inflammatory lesions and hyperplasia induced by NNK, was positive for macrophages and secretions in the alveoli spaces but less so in the walls of the alveoli. In the proliferative lesions including hyperplasia induced by DHPN, strong positive staining for napsin A was observed in the walls of the alveoli. Thus high expression was suggested to be possibly useful for detecting tumorigenic potential of rat lung hyperplasia.
    Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 11/2013; 66(2-3). DOI:10.1016/j.etp.2013.11.002 · 2.01 Impact Factor
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