Characterisation of oestrogen receptor, progesterone receptor, trefoil factor 1, and epidermal growth factor and its receptor in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma

Abstract

Background and aims: The pancreatic cystic neoplasms, including solid pseudopapillary tumour (SPT), mucinous cystic neoplasm (MCN), and intraductal papillary mucin producing tumour (IPMT), have their characteristic clinicopathological features. A systematic investigation of oestrogen receptor (OR), progesterone receptor (PR), trefoil factor 1(TFF1), and epidermal growth factor and its receptor (EGF and EGFR) expressed in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma was determined to elucidate their corresponding sex and age predilection, cell origin, and pathway of malignant transformation.

Methods: Surgical specimens of SPT (n=10), MCN (n=12), IPMT (n=10), and ductal adenocarcinoma (n=20) were studied. The expression of OR, PR, TFF1, EGF, and EGFR were each determined in each disease entity using monoclonal antibodies by immunohistochemical method. The results were correlated with the clinicopathological data.

Results: PR was expressed in all 10 SPT, whereas OR was expressed in none of 10 SPT. TFF1 was not or weakly expressed in SPT. Although EGF was strongly expressed in seven of 10 SPT, synchronous expression of EGF and its receptor was expressed in none of 10 SPT. Of the 12 MCN, six had PR expression in the stroma cells but not in the neoplastic epithelium, seven had a moderate or strong expression of TFF1, and 10 had no or weak EGFR expression, irrespective of their benigneity or malignancy. Synchronous expression of EGF and EGFR was observed in only one of 12 MCN. Among 10 IPMT, TFF1 and EGFR were moderately or strongly expressed in all six malignancies, whereas TFF1 and EGFR were not or weakly expressed in three of four benigneity. Of 20 ductal adenocarcinomas, TFF1 and EGFR were moderately or strongly expressed in 16 and 12, respectively. Synchronous expression of EGF and EGFR was observed in six of 10 IPMT and nine of 20 ductal adenocarcinoma, respectively.

Conclusion: PR was uniquely expressed in SPT, and OR and PR were expressed in stroma of MCN, reflecting their sex and age predilection. TFF1 expression was related to EGFR such as in IPMT and ductal adenocarcinoma, not related to EGFR such as in MCN, and not related to hormonal receptors such as in SPT. EGF and its receptor might play a part in the malignant transformation of IPMT and ductal adenocarcinoma, but not of SPT and MCN.

Figure 1

(A) Progesterone receptors (PR) were extensively expressed in the nuclei of cells of solid pseudo papillary tumours of the pancreas. (B) Oestrogen receptors were expressed in the nuclei of the stroma cells of mucinous cystic neoplasm (MCN) but not in the neoplastic epithelium. (C) PR were expressed in the nuclei of the stroma cells of MCN. (D) TFF1 were moderately expressed in the neoplasic epithelium of MCN. (E) Epidermal growth factor receptors (EGFR) were weakly expressed in MCN. (F) TFF1 were strongly expressed in intraductal papillary mucin producing tumour of the pancreas (IPMT). (G) EGFR were strongly expressed in IPMT. (H) TFF1 were moderately expressed in pancreatic ductal adenocarcinoma. (I) EGFR were strongly expressed in pancreatic ductal adenocarcinoma. (All panels original magnification ×100).

Figure 2

(A) Epidermal growth factor (EGF) were strongly expressed in solid pseudopapillary tumour of the pancreas (original magnification ×200). (B) EGF were not expressed in mucinous cystic neoplasm (original magnification ×100). (C) EGF were strongly expressed in pancreatic ductal adenocarcinoma. In this case, cancerous perineural invasion was noted, and EGF were expressed in the involved nerve fibres too (original magnification ×100). (D) Intraductal papillary mucin producing tumour of the pancreas (IPMT) with severe dysplasia histologically (haematoxylin and eosin stain, original magnification ×100). (E) EGF were strongly expressed in IPMT (the same as with D, original magnification ×200). (F) Epidermal growth factor receptor were moderately expressed in IPMT (the same as with D, original magnification ×100).