Significance of cellular distribution of ezrin in pancreatic cystic neoplasms and ductal adenocarcinoma.
OBJECTIVE
Pancreatic cystic neoplasms and ductal adenocarcinoma manifest diverse clinical features and prognoses, which might be related to cellular distribution of ezrin modulated through various trophic molecules.


METHODS
Laboratory investigation and retrospective analysis.


METHODS
Medical school-affiliated university hospital.


METHODS
Patients with solid pseudopapillary tumor (SPT) (n = 12), mucinous cystic neoplasm (MCN) (n = 18), intraductal papillary mucinous tumor (IPMT) (n = 18), and ductal adenocarcinoma (PA) (n = 73) of the pancreas were studied. Expression of epidermal growth factor (EGF) and its receptor (EGFR) and ezrin were determined using immunohistochemistry. Epidermal growth factor receptor and ezrin expression in sodium butyrate (SB)-treated PA cell line PANC-1 was determined using immunocytochemistry. Messenger RNA expression of ezrin in the PANC-1 cell line treated with SB was determined using reverse transcriptase-polymerase chain reaction. Multivariate analysis of survival of patients with PA was performed.


RESULTS
None of 12 SPTs displayed synchronous expression of EGF and EGFR, while all 3 malignant SPTs displayed membranous ezrin expression. One of 18 MCNs displayed synchronous expression of EGF and EGFR, while 4 of 6 borderline malignant and 8 of 8 malignant MCNs displayed membranous ezrin expression. Two of 4 borderline malignant and 11 of 11 malignant IPMTs displayed synchronous expression of EGF and EGFR, and all borderline malignant and malignant IPMTs displayed membranous ezrin expression. Less differentiated PA displayed EGF, EGFR, and membranous ezrin expression more frequently compared with more differentiated PA. Epidermal growth factor receptor expression of PANC-1 cells decreased in an SB dose dependent manner, in which PANC-1 cells became more differentiated and membranous ezrin expression of PANC-1 cells decreased correspondingly. Messenger RNA expression of ezrin in PANC-1 cells also decreased in an SB dose dependent manner. Patients with PA with membranous ezrin expression had a poorer prognosis compared with those without (P = .02).


CONCLUSIONS
Membranous translocation of ezrin might play a role during malignant transformation of SPT, MCN, IPMT, and PA, which are either dependent on (IPMT and PA) or independent of (SPT and MCN) the EGF-EGFR pathway. Membranous ezrin expression represents a prognostic factor for PA.
Yeh
Ta-Sen
TS
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. surglab@adm.cgmh.org.tw
Tseng
Jeng-Hwei
JH
Liu
Nai-Jen
NJ
Chen
Tse-Ching
TC
Jan
Yi-Yin
YY
Chen
Miin-Fu
MF
D002288:Adenocarcinoma, Mucinous / Q000737:chemistry*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry*; D003598:Cytoskeletal Proteins; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000737:chemistry*; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000737:chemistry; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000099149:Ezrin
D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D010750:Phosphoproteins; D012333:RNA, Messenger; D000099149:Ezrin