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

Pancreatic cancer (PC), a lethal condition with a poor prognosis, ranks fourth among the most common causes of cancer-related mortality as early diagnosis of PC is so tricky. Consequently, most cases at the time of initial diagnosis already harbor metastasis. PC cases' early detection and survival depend mainly on improving diagnostic approaches. This review sheds light on the role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a minimally invasive method in early PC diagnosis and differentiation between different pancreatic lesions. The discovery of new diagnostic and prognostic markers for PC will raise the accuracy of proper diagnosis, and in turn, patients will gain better survival and prognosis. Insulin-like growth factor II mRNA binding protein3 (IMP3) is overexpressed in several malignant tumors, including pancreatic cancer, which may raise its role in diagnosis and prognosis as well as its therapeutic benefit for PC.

Expression of IMP3 in benign and malignant thyroid tumor / 临床与实验病理学杂志

Purpose To investigate the expression of insulin-like growth factor Ⅱ mRNA-binding protein 3 (IMP3) and its differential diagnostic significance in benign and malignant thyroid tumor. Methods The fluorescent quantitative PCR and immunohistochemical staining were used to detect the IMP3 expression in 71 cases of thyroid tissue of different pathological types. The differential diagnostic significance of IMP3 expression in benign and malignant thyroid tumor was analyzed. Results Compared with normal thyroid tissue, thyroid tumors including follicular variant of papillary thyroid carcinoma (FVPTC ), follicular thyroid carcinoma (FTC), papillary thyroid carcinoma(PTC), nodular goiter (NG), and follicular adenoma (FA) had significantly higher IMP3 mRNA expression levels with10.13, 8.81, 8.52, 2.46, and 1.49 holds, respectively. The positive expression rate of IMP3 protein in thyroid tumors were significantly higher, with the positive rate from high to low was FTC (100％ ), PTC (96.77％ ), FVPTC (90％ ), FA(20％ ), and NG (0). The expression level of IMP3 protein was positively correlated with the expression of mRNA (P＜0.01). The IMP3 expression level of malignant thyroid tumor(8.82 holds) was significantly higher than that of benign thyroid tumor (1.94 holds) (P＜0.01). The IMP3 expression level of malignant thyroid follicular lesions (9.36 holds) was higher than that of benign thyroid follicular lesions (1.49 holds) (P＜0.01). Conclusion IMP3 may be an effective and useful molecular maker for diagnosis of benign and malignant thyroid neoplasms, as well as the differential diagnosis between benign and malignant thyroid follicular lesions.

Insulin-like growth factor Ⅱ mRNA binding protein 3 expression in the non-muscle invasive bladder cancer and its relationships with the prognosis / 中华泌尿外科杂志

Objective To investigate the expression of insulin-like growth factor Ⅱ mRNA binding protein 3 (IMP3) in non-muscle invasive bladder cancer and its relationship with the tumor recurrence and progression.Methods IMP3 protein expression was detected by immunohistochemistry in 130 cases of nonmuscle invasive bladder cancer specimens who underwent transurethral resection the first time at Beijing Chao-Yang hospital,from October 2010 to October 2013.Besides,we analyzed 20 cases of muscle-invasive samples and 20 benign tissues adjacent to cancer as control.The 130 patients were followed up by telephone and other methods.According to the UICC-TNM standard.Survival analysis was calculated by using the Kaplan-Meier method,and the difference in survival curves was analyzed by using the log-rank test.For multiple analyses,The Cox proportional hazards regression model was used.Results The positive expression rate of IMP3 in 130 patients with non-muscle invasive bladder cancer was 59.2％ (77/130),of which 30.0％ (39/130) was weak expression,29.2％ (38/130) was strong.However there was 80.0％ (16/20) in muscle-invasive specimens,of which 20.0％ (4/20) was weak,60.0％ (12/20) was strong (P =0.011).IMP3 was not detected in all benign tissues adjacent to cancer (P ＜0.001).All the 130 patients were followed-up for 5 to 69 mnonths,45 cases experienced disease recurrence,20 patients had progressed and 12 cases died.IMP3 expression was significantly related to higher tumor stage (P ＜ 0.001),high tumor grade (P =0.014),and tumor recurrence (P =0.003).Kaplan-Meier plots and log-rank tests showed that patients with IMP3-positive tumors had a lower disease-free survival (P =0.002) and progression-free survival rate (P =0.010) than those with IMP3-negative tumors.In the multivariable Cox analysis,we found that IMP3 protein was an independent predictor of disease-free survival (P =0.010) in non-muscle invasive urothelial carcinoma of bladder.Conclusions IMP3 was not expressed in benign tissue adjacent to cancer,whereas highly expressed in bladder cancer,and high IMP3 expression is an independent prognostic factor in NMIBC that can identify the patients with a high potential to relapse.

IMP3 and CD44 protein expression in recurrent bladder urothelial carcinoma / 中国肿瘤临床

Objective:To evaluate the expression of IMP3 and CD44 proteins in recurrent urothelial carcinoma (UC) and to deter-mine the correlation between the two proteins. Methods: Data from transurethral resection of bladder (TURB) cancer cases between January 2002 and December 2012 were reviewed. Of the 54 UC recurrent cases in this study, one group of 25 had experienced recur-rence within 6 months after surgery, and the other group of 29 had their first recurrence after more than 3 years. IMP3 and CD44 immu-noreactivities were increased, which correlated with the clinicopathologic parameters. The relationship between IMP3 and CD44 pro-tein expressions was also explored. Results:Six of the 25 short-term recurrent UC cases were tested positive for IMP3 and all belonged to high-grade UC. Among the 29 long-term recurrent patients, only one case of low-grade UC tested positive for IMP3. IMP3 expres-sion rate [24%(6/25)] and intensity [weak staining at 16%(4/25) and strong staining at 8%(2/25)] were higher in the short-term recur-rent group than those in the long-term group, which had an expression rate of 3.45% (1/29) and intensity rates for weak staining at 3.45%(1/29) and without strong staining (0/29). No difference was observed in the CD44 expression between the two groups. In addi-tion, the high expression of IMP3 correlated with higher tumor stage and grade, whereas the CD44 expression tended to be inversely correlated with the tumor grade in recurrent UC patients. Furthermore, no correlation existed between the expression of IMP3 and CD44 proteins in the bladder carcinoma specimens. Conclusion:IMP3 exhibited a significantly higher expression rate in short-term re-current UC specimens than in the long-term recurrent cases. Therefore, IMP3 could be used as a novel marker, together with the other factors including tumor stage and grade, for predicting the high risk of short-term recurrence in UC patients who underwent TURB.

Expression of insulin-like growth factor-Ⅱ mRNA-binding protein 3 in preeclamptic placen-tas / 临床与实验病理学杂志

Purpose To detect the expression of insulin-like growth factor-ⅡmRNA-binding protein 3 (IMP3) in preeclampsia (PE) placentas. Methods The levels of IMP3 expression were measured using immunohistochemistry in 8 cases of mild PE, 41 cases of se-vere PE, 6 cases of fetal growth restrict ( FGR) without PE and 22 cases of normal late trimester of pregnancy placentas. Results Compared with normal late trimester of pregnancy, the expression of IMP3 was obviously decreased in severe PE placenta ( Z =-2. 063,P0. 05). The expression of IMP3 in severe PE placenta was lower than that of mild PE placenta but not statistically significant (Z= -0. 233,P>0. 05). The expression of IMP3 in early onset PE placenta was lower than that of late onset PE placenta but not statistically significant(Z= -0. 108,P>0. 05). Compared with normal late tri-mester of pregnancy, the expression of IMP3 was significantly decreased in PE with FGR placenta (Z= -2. 375,P 0. 05, Z= -1. 36,P>0. 05). Conclusion The results indicate that IMP3 protein expression is low in sever PE, which may be one of the pathogenesis of PE. IMP3 may be used as a marker to predict PE with FGR, and to provide a basis for the development of a novel therapeutic target in PE.

Clinical significance on expression of IMP3 and CD44v6 in papillary thyroid carcinoma / 国际外科学杂志

Objective To investigate expression,significance and relationship of IMP3 and CD44v6 protein in papillary thyroid carcinoma.Methods Immunohistochemical method was used to investigate the expression of IMP3 and CD44v6 protein in 30 cases PTC(10 follicular variant of papillary carcinoma cases,20 conventional papillary thyroid carcinoma cases),20 PTC with lymph node metastasis cases,20 benign tissues of thyroid cases.Quantitative analysis of the detection was conducted by Biosens Digital Imaging System vl.6 (professional image analysis software),and the target integral optical density (IOD) was used for the judgement parameter.Results IMP3 and CD44v6 expression in the PTC is higher than in benign group,the difference was statistically significant (P ＜ 0.05) ; IMP3 and CD44v6 expression in PTC with lymph node metastasis was higher than without lymph node metastasis in the organization to express,the difference was statistically significant (P ＜ 0.05) ; There was a positive correlation between IMP3 and CD44v6 expression and metastasis in PTC (r =0.903,P ＜ 0.05).Conclusions The expression of IMP3 and CD44v6 protein was closely correlated with the invasion and metastasis of PTC.IMP3 and CD44v6 protein might be considered as molecular markers for PTC.

Expression and significance of insulin like growth factor-Ⅱ mRNA binding protein3 (IMP3) in gastrointestinal stromal tumors / 实用医学杂志

Objective To investigate the expression and significance of Insulin like growth factor-ⅡmRNA binding protein3 (IMP3) in gastrointestinal stromal tumors (GIST). Methods One hundred and fifteen cases of GIST were subjected to immunohistochemical staining for IMP3 (SP method) and ki67 (iVisionTM method ). The relationship between IMP3 expression with clinicopathologic parameters and Ki67 proliferation indexes were analyzed. In situ hybridization detection of IMP3 mRNA was performed in 20 cases of GIST positive. Results The expression rate of IMP3 was 56.2%(65/115) in GIST positive. A significant correlation can be found between IMP3 expression and tumor of infiltration , coagulative necrosis , metastasis , nuclear atypia , diameter , mitotic count , risk grade of NIH (P 0.05). There was positive correlation of IMP3 expression and Ki67 labeling indexes by Spearman analysis. Positive expression with IMP3 can be observed in 3 cases of recurrence.It may play important role in invasive and development and may be an important factor of prognosis in GIST.

IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma

BACKGROUND: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes. METHODS: We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed. RESULTS: Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival. CONCLUSIONS: IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.

Expression of IMP3 and its clinicopathological significance in breast cancer / 中华内分泌外科杂志

ObjectiveTo study the expression of insulin-like growth factor Ⅱ mRNA-binding protein 3 ( IMP3 ) and its clinicopathological significance in breast cancer.MethodsThe Maxvision immunohistochemistry was used to detect the expression of IMP3 protein in 103 cases of breast cancer and the adjacent normal breast tissues.Stem-loop real-time RT-PCR was used to detect the expression level of IMP3 mRNA in 30 cases of breast cancer and the matched non-tumor adjacent tissues.The relationship between the expression of IMP3 and the clinicopathological features of breast cancer was analyzed.Results62 cases were infiltrative ductal carcinoma,3cases were invasive lobular carcinoma,9 cases were microinfiltrative intraductal carcinoma,and 29 cases were special type of carcinoma.The difference of IMP3 expression between breast cancer group and normal breast tissue group had statistical significance( t =19.630,P =0.000)by t test.For infiltrative ductal carcinoma patients,IMP3 expression had no significant relation with age,tumor size,lymph node metastasis,histological grade,pTNM stage,ER,PR,or HER-2 ( P ＞ 0.05 ).IMP3 mRNA expression level of was significantly higher in tumor tissues than in the adjacent normal tissues (P ＜ 0.05 ).No significant association was found between the expression of IMP3 and the histological grade,tumor size,lymph node metastasis ( P ＞ 0.05 ).ConclusionIt is possible that IMP3 plays an important role in the generation,progression,invasion and metastasis of breast cancer.

Expression of insulin-like growth factor Ⅱ mRNA-binding protein 3 in transitional cell carcinoma of bladder and its clinical significance / 中国综合临床

Objective To investigate the expression of insulin-like growth factor Ⅱ mRNA-binding protein 3( IMP3 ) in transitional cell carcinoma of bladder( TCCB ) and its clinical significance. Methods The IMP3 expressions in 6 normal bladder tissues and 48 TCCB tissues were determined by immunohistochemistry staining, and the relationships between IMP3 expression and gender, age, pathological grading and staging were analyzed statistically. Results The positive expression rate of IMP3 was 62.5% ( 30/48 ) in bladder cancer,which were significantly higher than that in normal control ( 0/6 ) ( P ＜ 0. 05 ). The positive rate of IMP3 expression were significantly lower in superficial TCCB ( 46. 15%, 12/22 ) or early TCCB [ Grade Ⅰ 12. 5%(1/8) ,Grade Ⅱ 60. 0% (12/20) ] than that in invasive TCCB [T2 or above,81.8% (18/22) ] or advanced TCCB [ Grade Ⅲ ,85% ( 17/20 ) ] ( Ps ＜ 0. 05 ). Conclusion IMP3 is a promising biomarker for eraly detection and assessment of the malignancy degree in TCCB.

Insulin-like Growth Factor II mRNA-Binding Protein 3 Expression in Benign and Premalignant Lesions and Carcinomas of the Stomach

BACKGROUND: Recent studies have demonstrated that insulin-like growth factor II mRNA-binding protein 3 (IMP3) is expressed in malignant tumors of various organs but not in normal tissue. We investigated IMP3 expression in various benign lesions, premalignant lesions and carcinomas of the stomach. METHODS: IMP3 immunohistochemical staining was performed on 24 benign gastric lesions, 24 gastric adenomas, and 322 gastric carcinomas. RESULTS: IMP3 was not expressed in benign gastric lesions including adenomas with low-grade dysplasia, but was expressed in 17% of adenomas with high-grade dysplasia, and in 44% of carcinomas. As the carcinomas were in the advanced stage, they expressed IMP3 more frequently and strongly. Patients with IMP3-positive tumors had poorer survival than those with negative tumors. CONCLUSIONS: IMP3 expression in gastric carcinoma may be related to tumor invasion and metastasis, and is an independent risk factor for poor prognosis.

IMP3 Expression of the Cholangiocarcinoma in Cytology Specimen and Its Diagnostic Value

BACKGROUND: Pathologists occasionally have difficulty in distinguishing cholangiocarcinoma from benign reactive cells on the biliary cytology. We estimated the diagnostic value of insulinlike growth factor II mRNA binding protein 3 (IMP3) on biliary cytology specimens. METHODS: We selected 40 patients who had undergone a biliary cytology examination and whose diagnoses were confirmed by biopsy. The IMP3 expression was evaluated by immunohistochemical staining in both the tissue and the cytology specimens. Their histologic diagnoses were cholangiocarcinoma (n = 34), high grade dysplasia (n = 2), low grade dysplasia (n = 1) and non-biliary tumor or no tumor (n = 3). RESULTS: On the histology, all the cases of cholangiocarcinoma or high grade dysplasia were positive for IMP3 (36/36). The low grade dysplasia or the normal bile ducts in the other 4 cases were negative for IMP3 (0/4). Of the 36 cases diagnosed as cholangiocarcinoma or high grade dysplasia histologically, 29 cases were positive for IMP3 on the cytology (29/36; sensitivity, 80.6%). Of the 4 cases without cholangiocarcinoma or high grade dysplasia, 1 case was weakly positive for IMP3 on the cytology. The histologic diagnosis of this case was hepatocellular carcinoma. Except for this hepatocellular carcinoma case, the specificity of IMP3 on the cytology was 100%. CONCLUSIONS: IMP3 is a useful diagnostic marker for cholangiocarcinoma on cytology.

IMP3 expression and its relationship with clinicopathological characteristics in breast carcinoma / 临床与实验病理学杂志

Purpose To investigate the expression of IMP3 and its relationship with clinicopathological characteristics in breast cancer.Methods By the tissue microarray technique and immunohistochemical EliVision two-step method, expression of IMP3 was detected in 214 cases of breast carcinoma.Results Of the 214 breast cancer cases,IMP3 expression was seen in 31(14.49%). IMP3 expression in the tumor cells was positively correlated with histological grade (P=0.005), proliferative index labeled by Ki-67 (P=0.033) and triple negative phenotype (P0.05).Conclusions Expression of IMP3 is correlated with higher histologic grade, higher proliferative activity and triple negative breast carcinoma.Our findings indicate that IMP3 plays an important role in breast cancer progression, and IMP3 could be an adjuvant diagnostic marker in triple negative breast carcinoma.