Insulin-like growth factor 2 binding protein 3 expression on endoscopic ultrasound guided fine needle aspiration specimens in pancreatic ductal adenocarcinoma

Abstract

Background: Despite numerous investigations, we still do not have a specific marker for pancreatic ductal adenocarcinoma. Only guideline-recommended biomarker for pancreatic ductal adenocarcinoma is the CA19-9, but it is also present in other gastrointestinal diseases. IMP3 is a new potential biomarker that is over-expressed in some cancers. The aims of our study were (1) to assess IMP3 in benign pancreatic lesions and pancreatic cancer, and (2) to estimate its concentrations in localized and advanced pancreatic cancer. Patients and methods: Seventy-five patients with solid pancreatic lesions who underwent EUS-FNA were included. Patients were divided into three groups: benign lesions, cancer localized only on the pancreas, and patients with advanced pancreatic cancer (locally advanced or with distal metastases). Immunoreactivity of IMP3 was assessed on cytological smears sampled by endoscopic ultrasound. Results: IMP3 was expressed in 89% of the patients with pancreatic cancer and not in benign lesions. Stronger expression of IMP3 protein and stage of the pancreatic cancer was statistically significant. IMP3 was expressed in all localized cancers and in 85% of patients with advanced pancreatic cancer. In the subgroup with locally advanced cancer, IMP3 was expressed in 88%, and in 83% of patients in the subgroup with distal metastasis (P = 0.007). In the present study, sensitivity was 89%, specificity 100%, with positive predictive value of 100% and negative predictive value of 63%. Conclusion: There is a positive correlation between IMP3 expression and TNM stages of the pancreatic cancer. Higher expression of IMP3 on EUS-FNA specimens can suggest poorer prognosis.

Role of Immunohistochemistry in Suspected Pancreatic Ductal Adenocarcinoma

“…To overcome problems related to misdiagnosis, several immunohistochemical antibodies have been evaluated; several reports have interpreted the diagnostic value of Maspin, IMP3, S100A, and S100P in the differential diagnosis of PDAC from normal/reactive pancreatic tissue. [15][16][17][18][19][20][21] By contrast, only few studies have evaluated TFFs proteins expression on FNAB. 11 Maspin is an epithelial-specific tumor suppressor gene, whose expression is commonly downregulated in invasive high-grade cancers.…”

“…19 A re-expression of IMP3 has been observed in a series of human malignancies, including PDAC. 19 Most studies showed that IMP3 expression is not tumor specific, although it is a good marker of malignancy. 19 The S100 protein belongs to a family of calcium binding proteins with 25 known members, all of which have a high degree of sequence and structural similarity.…”

“…19 Most studies showed that IMP3 expression is not tumor specific, although it is a good marker of malignancy. 19 The S100 protein belongs to a family of calcium binding proteins with 25 known members, all of which have a high degree of sequence and structural similarity. Recent studies have found that several S100-related proteins, including S100P and S100A4, are overexpressed in PDAC.…”

“…IMP3 is an oncofetal RNA-binding protein located on chromosome 7 p11.5. It is expressed during embryogenesis but not in most adult tissues 19 . A re-expression of IMP3 has been observed in a series of human malignancies, including PDAC 19 .…”

Research advances of N6‐methyladenosine in diagnosis and therapy of pancreatic cancer

“…Compared with cytohistology alone, cytohistological analysis combined with IMP3 staining had substantially higher diagnostic sensitivity, specificity, and accuracy in endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) samples 85 . Tadic et al and Mikata et al also confirmed these findings 90,91 …”