Abstract
Aims
Intraductal papillary mucinous neoplasms (IPMNs) differentiate in several histological directions, which are related to IPMNs' clinical behaviour. IPMNs' differentiation to the gastric foveolar epithelium/pyloric gland (PG) is well-known. However, no study has been conducted regarding the fundic gland (FG) differentiation. To determine the frequency of FG-differentiation and its relationship with IPMNs' clinicopathological features, 48 surgically resected IPMN cases consisting of 17 gastric (G), 15 intestinal (I), 10 pancreatobiliary (PB), and 6 oncocytic (O) subtypes were studied.
Methods and Results
Clinicopathological data, including histological tumour grade, immunohistochemical data for MUCs, pepsinogen I/II, and H.K-ATPase, as well as GNAS/KRAS status were analysed. FG-differentiation was assessed by pepsinogen I and H.K-ATPase, while pepsinogen II and MUC6 were utilised to identify the equivalent cell type of the normal FG. RT-PCR for PGA5/PGC (pepsinogen I/ II mRNA, respectively) and qRT-PCR for PGA5 were performed to confirm the immunohistochemistry results. Pepsinogen I expression was detected in 12.5% (6/48 cases) of total IPMN cases, of which 66.7% (4/6 cases) of O- and 20.0% (2/10 cases) of PB-IPMN were pepsinogen I-positive. No H.K-ATPase-positive cases were detected. Three O-cases with pepsinogen I expression showed similar histology to normal FG. RT-PCR and qRT-PCR confirmed the immunohistochemical results. All IPMNs with FG differentiation were O- or PB-subtype, histologically high grade, and without GNAS mutation.
Conclusions
IPMNs' differentiation to gastric FG relates to O-/PB-subtypes and with high grade. This is the first report describing IPMNs' differentiation to the FG and revealing its relationship with IPMNs' clinicopathological features.
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