Pancreatic cyst fluid protein expression profiling for discriminating between serous cystadenoma and intraductal papillary mucinous neoplasm.
BACKGROUND
Many patients with benign serous cystadenoma (SCA) of the pancreas will undergo resection because of the inability to reliably discriminate between SCA and premalignant mucinous cysts (intraductal papillary mucinous neoplasm [IPMN], mucinous cystic neoplasm [MCN]).


METHODS
Cyst fluid from patients with SCA (n = 15), non main-duct and noninvasive IPMN (n = 32), and noninvasive MCN (n = 12) was aspirated at the time of operative resection and analyzed. Commercially available and custom designed multiplex assays (Luminex) were performed using a biomarker panel developed for pancreatic cancer. Differential protein expression (fluorescence intensity, FI) was compared between the 3 groups for each protein (Wilcoxon rank sum test). Unsupervised sample clustering (hierarchical clustering) and supervised sample classification (prediction analysis for microarrays [PAM]) was then performed.


RESULTS
Differential protein expression (P < 0.05) was identified between SCA and IPMN (34/51 proteins, 67%) and between SCA and MCN (13/51 proteins, 25%). The majority of proteins were down-regulated in IPMN and MCN compared with SCA. The only proteins significantly overexpressed in the cyst fluid of patients with mucinous cysts were CEA (median FI: IPMN 11.4, MCN 13.0, SCA 5.3; P < 0.001, IPMN vs. SCA) and CA72.4 (median FI: IPMN 10.4, MCN 10.5, SCA 9.9; P = 0.003, IPMN vs. SCA). Unsupervised cluster analysis demonstrated distinct clustering of SCA and IPMN with some cross-over between MCN. Supervised sample classification with 14 proteins had an overall accuracy rate of 92% between SCA and IPMN.


CONCLUSIONS
In this study differential cyst fluid protein expression was observed between SCA and IPMN for the majority of proteins assessed and multimarker sample classification accurately discriminated between SCA and IPMN in 92% of patients.
Allen
Peter J
PJ
Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. allenp@mskcc.org
Qin
Li-Xuan
LX
Tang
Laura
L
Klimstra
David
D
Brennan
Murray F
MF
Lokshin
Anna
A
D002288:Adenocarcinoma, Mucinous / Q000737:chemistry / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000175:diagnosis*; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000175:diagnosis*; D020420:Cyst Fluid / Q000737:chemistry*; D018293:Cystadenoma, Serous / Q000737:chemistry / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D040081:Protein Array Analysis
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins