Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma.
OBJECTIVE
Prognostic markers for pancreatic ductal adenocarcinoma (PDA) have failed to accurately predict patient prognosis. Recently, interest has developed in the accuracy of integrin-associated PINCH protein expression in human cancers as a predictive marker of tumour status. The goal of this study was to define the expression of PINCH protein in PDA.


METHODS
Human PDA samples and orthotopic tumours from a murine model were analysed by immunohistochemistry for PINCH expression. In the animal model, PINCH expression was compared between primary and metastatic tumours. In the human samples, PINCH expression was correlated with stage, nodal involvement, margin status and overall survival.


RESULTS
In the murine model, there was greater PINCH expression in metastatic tumours than in primary tumours. In the human PDA samples, greater staining for PINCH in the tumour cells was correlated with higher T status. Additionally, high PINCH expression in the stroma was associated with decreased overall survival.


CONCLUSIONS
Findings of increased PINCH protein in more advanced stages of human PDA, as well as in metastatic tumours in the animal model, support the hypothesis that PINCH is an important controller of cell survival and migration. Additionally, the importance of the differential expression of PINCH in the human tumour and stroma warrants further evaluation.
Scaife
Courtney L
CL
Department of Surgery, University of Utah, Salt Lake City, UT 84132, USA. courtney.scaife@hci.utah.edu
Shea
Jill
J
Emerson
Lyska
L
Boucher
Kenneth
K
Firpo
Matthew A
MA
Beckerle
Mary C
MC
Mulvihill
Sean J
SJ
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016577:Pancreaticoduodenectomy; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C088088:LIMS1 protein, human; D008565:Membrane Proteins