Presence of pancreatic intraepithelial neoplasia‐3 in a background of chronic pancreatitis in pancreatic cancer patients

Abstract

The clinical significance of pancreatic intraepithelial neoplasia (PanIN) lesions in non-neoplastic pancreata of pancreatic ductal adenocarcinoma (PDAC) patients remains controversial. As chronic inflammation has been recently demonstrated to promote dissemination of in situ precancerous lesions, we investigated the prognostic significance of PanINs associated with chronic pancreatitis (CP) in PDAC patients. This retrospective study analyzed 125 curatively resected PDAC specimens for the presence of PanIN and CP. Univariate and multivariate analyses were performed to identify significant predictive factors for poor disease-free survival (DFS) and overall survival (OS). Immunohistochemical staining for E-cadherin and S100A4, markers of epithelial-mesenchymal transition, was performed on resected specimens containing PanIN-3 lesions. CP was observed in 27.2% (34/125) and PanIN-3 in 25.6% (32/125) of specimens. In the presence of CP, PanIN-3 was significantly associated with decreased survival (DFS: 4.3 vs 15.5 months, P = 0.021; OS: 16.3 vs 30.9 months, P = 0.004). PanIN-3 was not a prognostic factor in the absence of CP. The presence of both PanIN-3 and CP was associated with a reduced survival compared to the other cases, in both univariate (DFS: P = 0.039; OS: P = 0.023) and multivariate (DFS: P = 0.020; OS: P = 0.076) analyses. Furthermore, E-cadherin loss and S100A4 expression were more frequently observed in PanIN-3 lesions of CP specimens than in those of non-CP specimens, although not statistically significant. PanIN-3 in association with CP is a significant prognostic factor for decreased survival in PDAC patients, suggesting that chronic inflammation may accelerate the progression of preinvasive high-grade PanIN.

MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

“…Pancreatic intraepithelial neoplasia (PanIN) is a precursor lesion of PDAC [ 30 , 31 ]. PDAC is usually accompanied by PanIN [ 32 ]. On TMA, we identified three PanINs together with PDAC or in non-tumor tissue.…”

Metabonomic changes from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma in tissues from rats

“…In the present study, all rats from experimental group I were diagnosed with PanIN‐2 but without PanIN‐1 or PanIN‐3. This is predictable because the identification of PanIN‐1, a very early lesion with low risk, is very difficult and PanIN‐3 is often observed in PDAC groups only due to the high invasiveness, especially with other promoters . Therefore, PanIN‐2 could be treated as the beginning of invasive progression leading to highly invasive PDAC .…”

“…This is predictable because the identification of PanIN-1, a very early lesion with low risk, is very difficult and PanIN-3 is often observed in PDAC groups only (24) due to the high invasiveness, especially with other promoters. (25) Therefore, PanIN-2 could be treated as the beginning of invasive progression leading to highly invasive PDAC. (26) Thus, the metabonomic profiles can be highly representative for that of PDAC at early stage.…”

Risk factors of pancreatic cancer and their possible uses in diagnostics

“…Pancreatic chronic inflammation appears to be an early step in the development of a malignancy, with genetic alterations occurring as a result of prolonged inflammatory processes [54]. This may be evidenced, among other proofs, by the fact that PanIN lesions (representing individual steps of oncogenesis) are more common in patients with CP than in the general population [55]. PC and smoking.…”