Pancreatic cancer (PC) is characterized by poor prognosis, decreased survival and inoperable advanced stages. Presenting at advanced stages is considered a crucial point in patients’ survival. Therefore, an early and accurate diagnosis is needed for those patients, hoping for early management that could improve prognosis and prolong survival. A study done by Pasiliao et al 2015 observed a decrease in motility, invasion, and matrix adhesion following IMP3 knockdown suggesting that IMP3 promotes PAC progression by enhancing the pro-metastatic behavior of tumor cells (12). Moreover, the immunohistochemical IMP3 expression was considered a poor prognostic predictor in different malignancies as mucoepidermoid carcinoma of salivary glands, duodenal papillary carcinoma and pilocytic and pilomyxoid astrocytomas (13–15).
Also confirming the diagnostic importance of IMP3, using quantitative real-time RT-PCR by Yantiss et al 2005 showed that mRNA IMP3 was highly expressed in pancreatic carcinomas (79%) (16). Also, Wang et al 2015 demonstrated that increased mRNA IMP3 expression was associated with poor overall survival and considered as an independent risk factor and they suggested that combination with microdissection techniques to evaluate IMP3 mRNA expression in frozen pancreatic lesions can be worthy for diagnosis of PC (17).
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) combined with evaluation of IMP3 immunohistochemical expression is a promising tool for achieving this goal. A meta-analysis study showed that the results of IMP3 immunostaining may be a useful diagnostic tool for confirming PAC but should be evaluated in parallel with the gold standard of histopathological morphology and clinical findings. Also IMP3 was suggested to be diagnostic tool for duodenal papillary carcinoma and endometrial cancers and their premalignant lesions (14, 18–19).
EUS approach is not only minimally invasive technique with low complications but also it provides us with high resolution images for different pancreatic lesions and may determine tumor stage. Many studies studied the combined diagnostic tool of (EUS-FNA) with IMP3 expression for discriminating malignant from benign lesions. As Yantiss et al 2008 demonstrated that EUS-FNA for PAC expressed IMP3 in 92% of the cases, while all cases of chronic pancreatitis were IMP3 negative (20). Zhao et al 2007 found that all benign cases expressed negative IMP3; IMP3 was expressed in 88% of PAC; suspicious cases were positive for IMP3; Cytology results combined with IMP3 expression revealed 95% positivity in PAC (21). IMP3 staining was positive in 97%, 79% of PAC, high grade dysplasia, respectively, while in mild to moderate dysplasia, IMP3 showed negative staining. Generally, IMP3 showed strong to moderate intensity (16). These results were agreeing with ours, as we found that high IMP3 was expressed in 77.8%, 78.7%, 91.7%, and 100% of SPN, PAC, mucinous neoplasm with high grade dysplasia, and IPMN with high grade dysplasia, respectively.
In low grade dysplasia, 2/6 cases of mucinous neoplasm and 3/6 cases of IPMN were positive for IMP3 staining. However, benign lesions showed negative staining in all cases of benign lesions except one case of serous microcystic adenoma and a case of autoimmune pancreatitis which were diagnosed by cytology as benign. Also, A study analyzed the expression of 26 immunohistochemical markers confirmed the diagnosis of PAC in both surgical and fine-needle aspiration specimens using the best diagnostic panel of immunomarkers including pVHL, maspin, S100P, and IMP3. IMP3 was 90% positive (intermediate to weak intensity) in PAC in surgical specimens and normal pancreatic ducts were usually negative for IMP-3, while in FNA specimens, IMP3 was positive in 93% of PAC compared with 77% and 10% for suspicious and benign cases, respectively (22).
The incidence of pancreatic cystic lesions is rising due to increase use of imaging techniques as part of routine clinical practice. Some cystic lesions have the potential for malignant neoplastic transformation and are considered malignant precursor for pancreatic ductal adenocarcinoma such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) whereas serous cystic neoplasms (SCNs) are considered benign lesions. Ezzat et al 2016 and Senoo et al 2018 demonstrated sensitivity, and specificity of IMP3 on cytology specimens for PAC were 91.2%, 86.7%, and 87.9%, 100%, respectively, with total accuracy 90.3% and 90.8%, respectively (23–24). Our findings concluded that using of combined IMP3 immunohistochemical staining with cytology diagnosis of malignant and benign pancreatic lesions has sensitivity, and specificity of 78.2% and 95.8% with total accuracy 84.3% compared with 64.1%, 100%, and 89% sensitivity, specificity, and total accuracy of cytology diagnosis only, respectively.
Limitations of the study:
Many problematic issues may arise due to limited skills of the endoscopy operator in terms of insufficient tissue yield and targeting-error, misinterpretation and misdiagnosis by pathologists and absence of on-site cytopathologists for adequacy assessment.
In conclusion, for diagnosing malignant pancreatic lesions, IMP3 expression based on EUS-FNA sampling could be very valuable. However, benign lesions rely more accurately on cytologic findings by EUS-FNA than IMP3 expression. Further research is recommended on largest samples of malignant and benign pancreatic lesions.