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.

Association of epidermal growth factor receptor and mitogen-activated protein kinase with cystic neoplasms of the pancreas

“…EGFR is overexpressed in a wide variety of epithelial neoplasms, including pancreatic cancer. 16,17 With regard to cystic neoplasms of the pancreas, Yeh et al 28 and Zhao et al 29 independently found that EGFR is infrequently expressed in the mucinous cystic neoplasms. However, there have been no published reports on EGFR expression in the serous cystic neoplasms.…”

Trefoil factor 1 acts to suppress senescence induced by oncogene activation during the cellular transformation process

“…A large number of studies indicate that TFF1 expression is absent or occurs at low levels in nonmalignant pancreatic and prostate tissues. Elevated expression levels of TFF1 are frequently observed in pancreatic and prostate malignancies (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), suggesting that TFF1 may be involved in the tumorigenesis of these cancers. These data are not, however, sufficiently convincing because of the lack of strict statistical analysis in some studies and the reduced statistical power in others with small sample sizes.…”

“…To gain insight into this question, we took a candidate approach by examining the possible involvement of known signaling pathway(s) initiated by plasma membrane-bound receptors for growth factors for mediation of TFF1 activity in the context of overcoming OIS. In this regard, previous reports indicated that TFF1 and EGFR are co-overexpressed in certain malignant tumors and that TFF1 might exert its activity through EGFR, although no definitive signaling pathways have been elucidated (31). To test if EGFR activity contributes to the ability of TFF1 to suppress OIS, we repeated the experiment using PrEC with Ras-induced OIS and recombinant TFF1 in the presence or absence of an EGFR inhibitor.…”

Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: An experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy

“…In animal models, sunitinib exhibits potent antitumor activity in glioblastoma, breast and lung tumors (28,29). In human PC, VEGFRs types 1-3 and PDGFRs · and ß are expressed and have been correlated with poor prognosis (30)(31)(32)(33). Also, recently, it was demonstrated in vitro and in vivo that sunitinib sensitized pancreatic cancer cells to the cytotoxic effects of radiation (34).…”