IMP3 Expression Research Articles

Prognostic Value of IMP3 Expression in Squamous Cervical Cancer.

Cervical cancer remains one of the leading causes of death from malignant diseases in women worldwide. Primary and secondary prevention have led to better outcomes in developed countries, whereas in developing countries, cervical cancer continues to be responsible for an unjustifiably high number of fatalities. The discovery of new tumor biomarkers can lead to earlier diagnosis, better therapeutic decisions, and improved treatment methods. IMP3 is a protein responsible for invasiveness and other aggressive characteristics of tumor processes. Its highly specific expression has been proven in various malignant processes. The level of IMP3 expression in cervical cancer cells could be used as a prognostic factor for a worse disease course. In this study, IMP3 expression was examined in 80 patients who underwent surgery for squamous cell cervical cancer in the first FIGO stage of the disease, and its association with disease-free period and overall survival was investigated. Data analysis did not show a statistically significant association between IMP3 expression and the mentioned primary outcomes, despite its association with clinical-pathological indicators of advanced disease. In conclusion, the analysis of IMP3 protein expression in patients with early-stage cervical cancer is of limited utility.

Expression of IMP3 and LIN28A RNA-Binding Proteins in Placentas of Patients with Pre-Eclampsia with and without Severe Features.

this study aimed to determine the expression of RNA-binding oncofetal proteins IMP3 and LIN28A in extravillous (EVT) and villous trophoblast (VT) cells of placentas from pre-eclamptic (PE) pregnancies to better understand the pathogenesis of PE. placental tissue of 10 patients with PE with severe features, 10 patients with PE without severe features and 20 age-matched healthy pregnancy controls were analyzed by immunohistochemistry, double immunofluorescence and qPCR. We found a decreased percentage of IMP3-positive EVT cells in PE with and without severe features compared to that of the healthy control (p < 0.001). IMP3 expression was significantly low in VT of PE placentas compared to that of the healthy control (p = 0.002). There was no significant difference in LIN28A expression between groups of PE and the control group. Additionally, we noticed the trend toward downregulation of IMP3 mRNA and LIN28A mRNA in severe PE compared to that of healthy controls. We demonstrated that IMP3 expression is decreased in EVT and VT cells of placentas from pregnancies complicated with both PE with and without severe features. However, additional functional investigations are needed to clarify the role of IMP3 as a potential therapeutic target in the management of PE.

Retraction: Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression.

Retraction: Enhanced IMP3 Expression Activates NF-кB Pathway and Promotes Renal Cell Carcinoma Progression.

The Role of IMP3 Immunohistochemistry Expression in Triple-negative Breast Cancer as a Prognostic Factor

Introduction: Triple-negative breast cancer (TNBC) accounts for 12%–18% of the breast malignancies. An insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is linked to a number of aggressive malignancies like TNBC. The aim of the study was to evaluate the correlation between IMP3 expression and histopathological parameters in TNBC. Materials and Methods: A prospective and retrospective study between January 2019 and June 2023 was done on 48 TNBC subjects with IMP3 expression. The Chi-square test is applied to investigate the correlations between categorical variables. The Kaplan–Meier (KM) method is applied for survival analysis. Results: Out of 48 subjects, 23 (47.9%) had negative staining, whereas 25 (52.1%) of them expressed strong staining to IMP3. The KM curve for disease-free survival showed that was almost same up to 35 months in both IMP3 negative and cases having strong staining features which was also found to be statistically significant. Conclusion: According to our findings, IMP3 can be employed as a risk predictor for TNBC. Focussing the IMP3 expression could be a viable strategy to managing TNBC with novel immune treatments that are currently unavailable.

IMP3, CDK4, MDM2 and β-catenin expression in Enchondroma and Central Chondrosarcoma: Diagnostic and prognostic utility

IntroductionThe role of IMP3, CDK4, MDM2 and β-catenin proteins in Enchondroma and Central Chondrosarcoma is not totally understood. The aim of this study is to evaluate the immunoexpression of these proteins, associating histological grade, clinical data and prognosis to these tumors. MethodsThis is a retrospective-analytical study of 32 Enchondroma and 70 Central Chondrosarcoma. ResultsIMP3, CDK4, MDM2 and β-catenin expression was observed in 22.82 %, 13.82 %, 17.17 % and in 8.8 % of cases, respectively. All Enchondromas positive for these immunomarkers were located in short tubular bones. The positivity for these antibodies is directly proportional to Chondrosarcoma's histological grade increase. No difference was found between Enchondroma and Chondrosarcoma, Grade 1 for IMP3, CDK4 and ß-catenin positivity. Significant metastasis outcome was observed for IMP3, CDK4, MDM2 and death for MDM2 expression. ConclusionIMP3, CDK4, MDM2 and β-catenin expression in Enchondromas of short bones phenotypically characterizes these tumors. Their expression has not proven to be useful either as diagnostic markers of these neoplasms or in distinguishing between Enchondroma and Chondrosarcoma, Grade 1. The significant immunoexpression of IMP3, CDK4 and MDM2 in metastatic Chondrosarcoma and the lower survival in those with positivity for MDM2 suggest a possible association of these proteins with tumor aggressiveness.

IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas

Introduction: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model. Materials and Methods: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up. Results: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules. Conclusions: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).

IMP3 Expression as a Potential Tumour Marker in High-Risk Localisations of Cutaneous Squamous Cell Carcinoma: IMP3 in Metastatic cSCC.

High IMP3 expression is correlated with a worse outcome. Until now, there have been no data about IMP3 expression and clinical outcome for high-risk localisation of squamous cell carcinoma of the skin (cSCC). One-hundred twenty-two patients with cSCC of the lip and ear were included, and IMP3 expression in the tumours was immunohistochemically assessed in different evaluation approaches. Subsequently, subgroups were analysed in a matched pair approach and correlated with clinical pathologic parameters. In the following, different IMP3 analysis methods were tested for clinical suitability. We found a significant correlation between IMP3 expression and risk for lymph node metastasis, local relapse, and progression-free survival. On basis of our data, we suggest a prognostic benefit cutoff value for high (>50%) and low (<50%) IMP3 expression. Thus, IMP3 expression has a high scientific potential for further studies and could potentially be used as a prognostic marker in diagnostic and therapeutic decision-making.

Bile duct adenoma and small-sized small duct type intrahepatic cholangiocarcinoma show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components.

Given that bile duct adenoma was significantly more prevalent in the liver with small duct type intrahepatic cholangiocarcinoma (small duct iCCA), compared to other primary liver carcinomas, we examined the possibility of bile duct adenoma as a precursor of small duct iCCA by analysing genetic alterations and other features in bile duct adenomas. Subjects included 33 bile duct adenomas and 17 small-sized (up to 2 cm in diameter) small duct iCCAs. Genetic alterations were examined by direct sequencing for hot-spot regions and immunohistochemical staining. The expression of p16INK4a , EZH2 and IMP3 and stromal and inflammatory components were also examined. Genetic alterations examined including BRAF were not detected in bile duct adenomas, whereas genetic alterations of p53 (47%), ARID1A (41%), PBRM1 (12%), MTAP (12%), IDH1 (6%), KRAS (6%) and TERT promoter (6%) were detected in 16 small-sized small duct iCCA (94%) (P < 0.01). The expression of IMP3 and EZH2 was not detected in bile duct adenomas, whereas it was detected in most small duct iCCA (94%) (P < 0.01). Immature stroma and neutrophilic infiltration were significantly more prevalent in small duct iCCA, compared to bile duct adenoma (P < 0.01). Bile duct adenomas and small-sized small duct iCCAs show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components. There was no evidence suggesting that bile duct adenoma is a precursor of small duct iCCA. Immunohistochemical staining for IMP3, EZH2, p53, ARID1A and MTAP may be useful for differential diagnosis between bile duct adenomas and small duct iCCAs.

A novel tumour enhancer function of Insulin-like growth factor II mRNA-binding protein 3 in colorectal cancer

CRC cells evolve a variety of strategies to limit or circumvent apoptosis cell death. RNA binding proteins (RBPs) regulate many of the molecular mechanisms that underlie the development of cancer. The insulin-like growth factor II mRNA-binding proteins (IMP) family are oncofoetal RBPs, consisting of IMP1, IMP2 and IMP3, which have an important role in RNA metabolism. IMP3 is highly expressed in colorectal cancer (CRC) tissue, where its expression often correlates with poor prognosis. However, the role of IMP3 in CRC is not fully understood. IMP3 expression was analysed using a public database and by Western blotting and immunohistochemistry in human colon samples derived from patients with sporadic CRC and healthy subjects. To address whether IMP3 controls cancer cell survival, we analysed cell death pathways in in vitro and in vivo experiments after IMP3 downregulation by siRNA or an antisense oligonucleotide. IMP3 was highly expressed in CRC samples compared to normal control tissues. The knockdown of IMP3 enhanced a caspase-independent cell death in CRC cell lines. Furthermore, the treatment of CRC cells with IMP3 siRNA did not alter the expression of GSDMD, GPX-4 and the activated form of RIP3, three key molecules that govern pyroptosis, ferroptosis and necroptosis, respectively. Abrogation of IMP3 in CRC significantly reduced Bcl-2 and Bcl-xL mRNA and was associated with an altered mitochondrial membrane potential that allowed the nuclear migration of the apoptosis-inducing factor (AIF). Moreover, specific immunoprecipitation experiments on CRC human cell lines indicated that IMP3 binds Bcl-2 and Bcl-xL mRNA, suggesting that IMP3 acts as a regulator of the intrinsic apoptotic pathway through the surveillance of anti-apoptotic Bcl mRNA metabolism. Finally, we showed that IMP3 block inhibited the growth of CRC cell lines in vivo after transplantation into immunodeficient mice. Altogether, these data support a novel role for IMP3 in controlling the intrinsic caspase-independent apoptotic pathway in CRC.

Insulin Like Growth Factor II mRNA-Binding Protein 3 (IMP3) Immunohistochemical Expression in Salivary Glands Tumors- Local Study

Objective: To identify the relationship between the expression of IMP3 in benign and malignant tumors of salivary glands and other clinic-pathological variables. Materials and Methods: Twenty-six cases of salivary gland tumors were collected from the histopathology department, Gazi-Hariri hospital/ Baghdad Medical City from January 2021 to June 2021. Patients’ reports were included for diagnosis and clinicopathological data. Three histological sections were taken from the paraffin blocks for each case. The first section was stained with H&amp;E stain, and the other two sections were stained with IMP3 (Dako-code M3626) monoclonal antibody by the immunohistochemical method. Results: Twenty-six cases of salivary gland tumor, with equal male/female distribution; the mean age for the patients was 45 years (19-60 years). There was no significant relationship between gender (P=.0.115), tumor size (P=0.359), tumor location (P=0.335), and tumor type (P=0.673) with positive expression of IMP3. Regarding malignant cases, no significant relation between IMP3 expression and tumor stage (P=1.000), and lymphovascular invasion (P=1.000). On the other hand, there was a highly significant relationship (P=0.000) between IMP3 expression and cell type (epithelial/mesenchymal). Conclusion: Imp3 might not be conclusive in differentiation between benign and malignant salivary gland tumors. Further studies with follow-up are needed to assess the prognostic value of this marker in salivary gland pathologies.

Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma.

Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma. We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5ml of peripheral blood samples collected from patients using the Canpatrol® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 (IMP3) expression in CTCs were analyzed. CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients (P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features (P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3-positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression. This study demonstrates that the CTCs, especially the IMP3-positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.

A comprehensive immunohistochemical analysis of IMP2 and IMP3 in 542 cases of ovarian tumors

BackgroundIMP2 and IMP3 are mRNA binding proteins involved in carcinogenesis. We examined a large cohort of ovarian tumors with the aim to assess the value of IMP2 and IMP3 for differential diagnosis, and to assess their prognostic significance.MethodsImmunohistochemical analyses with antibodies against IMP2 and IMP3 were performed on 554 primary ovarian tumors including 114 high grade serous carcinomas, 100 low grade serous carcinomas, 124 clear cell carcinomas, 54 endometrioid carcinomas, 34 mucinous carcinomas, 75 mucinous borderline tumors, and 41 serous borderline tumors (micropapillary variant). The associations of overall positivity with clinicopathological characteristics were evaluated using the chi-squared test or Fisher’s Exact test.ResultsWe found IMP2 expression (in more than 5% of tumor cells) in nearly all cases of all tumor types, so the prognostic meaning could not be analyzed. The positive IMP3 expression (in more than 5% of tumor cells) was most common in mucinous carcinomas (82%) and mucinous borderline tumors (81%), followed by high grade serous (67%) and clear cell carcinomas (67%). The expression was less frequent in endometrioid carcinomas (39%), low grade serous carcinomas (23%), and micropapillary variant of serous borderline tumors (20%). Prognostic significance of IMP3 could be evaluated only in low grade serous carcinomas in the case of relapse-free survival, where negative cases showed better RFS (p = 0.033).ConclusionConcerning differential diagnosis our results imply that despite the differences in expression in the different ovarian tumor types, the practical value for diagnostic purposes is limited. Contrary to other solid tumors, we did not find prognostic significance of IMP3 in ovarian cancer, with the exception of RFS in low grade serous carcinomas. However, the high expression of IMP2 and IMP3 could be of predictive value in ovarian carcinomas since IMP proteins are potential therapeutical targets.

MiR-196a enhances polymerization of neuronal microfilaments through suppressing IMP3 and upregulating IGF2 in Huntington’s disease

Huntington's disease (HD) is one of the inheritable neurodegenerative diseases, and these diseases share several similar pathological characteristics, such as abnormal neuronal morphology. miR-196a is a potential target to provide neuroprotective functions, and has been reported to enhance polymerization of neuronal microtubules in HD. While microtubules and microfilaments are two important components of the neuronal cytoskeleton, whether miR-196a improves neuronal microfilaments is still unknown. Here, we identify insulin-like growth factor 2 mRNA binding protein 3 (IMP3), and show that miR-196a directly suppresses IMP3 to increase neurite outgrowth in neurons. In addition, IMP3 disturbs neurite outgrowth invitro and invivo, and worsens the microfilament polymerization. Moreover, insulin-like growth factor-II (IGF2) is identified as the downstream target of IMP3, and miR-196a downregulates IMP3 to upregulate IGF2, which increases microfilamental filopodia numbers and activates Cdc42 to increase neurite outgrowth. Besides, miR-196a increases neurite outgrowth through IGF2 in different HD models. Finally, higher expression of IMP3 and lower expression IGF2 are observed in HD transgenic mice and patients, and increase the formation of aggregates in the HDcell model. Taken together, miR-196a enhances polymerization of neuronal microfilaments through suppressing IMP3and upregulating IGF2 in HD, supporting the neuroprotective functions of miR-196a through neuronal cytoskeleton in HD.

Immunohistochemical Expression of IMP3 in Cutaneous Basal Cell Carcinoma

Background. Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is an oncofetal protein upregulated in tumor cells during carcinogenesis. It has been linked to adverse clinical outcome in many malignancies.&#x0D; This study was aimed to evaluate an immunohistochemical expression status of IMP3 in cutaneous basal cell carcinoma (BCC) and to correlate it with the Ki-67 index values.&#x0D; Methods. Biopsy specimens from 32 cases of BCC were enrolled into this analysis. All samples were immunohistochemically stained for IMP3 (Clone 69.1) and Ki-67 antigen (Clone MIB-1).&#x0D; Results. IMP3 showed a weak expression in 11 (34.4%) cases, a moderate expression in 11 (34.4%) cases, a strong expression in 5 (15.6%) cases, and negative staining in 5 (15.6%) cases. Among seven BCCs exhibiting aggressive-growth features, all but one showed weak reactivity. In contrast, all five BCCs manifesting strong IMP3 positivity consisted of the indolent-growth histologic subtypes. BCCs with infiltrative histomorphology did not appear to have a tendency towards more striking production of IMP3. There was no significant relationship between the IMP3 expression status and the proliferation status (Ki-67 ≤ 50% vs. Ki-67 &gt; 50%) of the tumor tissue (p &gt; 0.05).&#x0D; Conclusions. The vast majority of cutaneous BCCs express IMP3, suggesting this oncoprotein is implicated in BCC carcinogenesis. However, more pronounced expression does not seem to be associated with aggressive-growth phenotype of BCC or higher proliferative activity of neoplastic cells.

IMP3 Expression in Thyroid Cancers and its Relationship with Prognostic Parameters

To determine the expression of IMP3 (Insulin-like growth factor-II mRNA binding protein 3), which has been reported to be associated with poor prognosis in many organ malignancies, in thyroid malignant tumors and to determine its relationship with prognostic factors such as age, gender, tumor size, and histological type of tumor.

Prognostic relevance of immunohistochemical expression of Sox2, YAP1, and IMP3 in non-muscle invasive bladder cancer

Prognostic relevance of immunohistochemical expression of Sox2, YAP1, and IMP3 in non-muscle invasive bladder cancer

Immunohistochemistry of the oncofetal protein IMP3 is helpful in the diagnosis of intravascular large B-cell lymphoma using skin biopsy.

The oncofetal protein insulin-like growth factor 2 mRNA binding protein-3 (IMP3) is expressed in various cancers. In this study, we examined the diagnostic utility of IMP3 immunohistochemistry in the context of intravascular large B-cell lymphoma (IVL). We obtained 25 skin biopsy (SB) specimens diagnosed as IVL and nine IVL-negative SB specimens from 27 IVL patients. Additionally, 27 negative SB specimens from 26 non-IVL patients were obtained from our pathology archives. We performed IMP3 immunohistochemistry on these 61 SB specimens, considering IMP3 expression in any mononuclear cell as positive. In selected cases, triple immunostaining for IMP3, PAX5, and CD34 was performed to analyze the origin and location of IMP3-positive cells. IMP3 was expressed in most intravascular lymphoma cells in all the 25 SB specimens diagnosed as IVL. Furthermore, our evaluation revealed the presence of intravascular IMP3-positive B-cells in five of the nine negative SB specimens from IVL patients; however, this was not observed in the 27 SB specimens from non-IVL patients. IMP3 was expressed in most IVL cells, and IMP3 immunohistochemistry could serve as a sensitive diagnostic aid for detecting IVL cells in SB.

Diagnostic value of IMP3 expression in colorectal carcinoma and adenoma

Diagnostic value of IMP3 expression in colorectal carcinoma and adenoma

Value of immunohistochemical IMP3 expression with endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) in diagnosing pancreatic lesions: Review Article

Value of immunohistochemical IMP3 expression with endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) in diagnosing pancreatic lesions: Review Article

Immunohistochemical Study of IMP3 Expression in Laryngeal Squamous Cell Carcinoma

BACKGROUND: IMP3 is an RNA binding protein, which is strongly expressed in malignant tumors, promoting tumor cell proliferation. AIM: The aim of the study was to evaluate the expression of IMP3 in laryngeal squamous cell carcinoma (SCC) and to correlate the expression of IMP3 with available clinicopathological data. METHODS: Sixty one total laryngectomy and laryngoscopic biopsies; collected from the Pathology Department, Faculty of Medicine, Cairo University. Two slides were prepared from each paraffin embedded tumor block, one slide for Hematoxylin and Eosin staining, and the other for immunohistochemical staining by IMP3 polyclonal antibody. RESULTS: Thirty-seven cases (60.7%) showed positive IMP3 expression, and a statistically significant correlation was found between IMP3 expressions in normal, dysplastic epithelium/in situ component, and the invasive malignant tumor tissue. Correlations between IMP3 expression and other available clinicopathological data were all non-significant. CONCLUSION: This study suggests that IMP3 might play a role in laryngeal SCC carcinogenesis and progression process from normal to dysplastic to malignant epithelium, and thus IMP3 might be targeted by gene therapy.