Pancreatic cyst fluid and serum mucin levels predict dysplasia in intraductal papillary mucinous neoplasms of the pancreas.
BACKGROUND
There are no reliable markers of dysplasia in patients with incidentally discovered intraductal papillary mucinous neoplasms of the pancreas (IPMN). IPMN dysplasia may be associated with mucin protein (MUC) expression and histopathologic subtype. We hypothesize that MUC expression in cyst fluid and serum can identify lesions with high risk of malignancy.


METHODS
Cyst fluid and serum were collected from 40 patients during pancreatectomy for IPMN between 2005 and 2009. Samples were grouped into low-risk (low-grade or moderate dysplasia, n = 21) and high-risk groups (high-grade dysplasia or carcinoma, n = 19). Mucin expression (MUC1, MUC2, MUC4, and MUC5AC) was assessed utilizing enzyme-linked immunosorbent assays.


RESULTS
MUC2 and MUC4 cyst fluid concentrations were elevated in high-risk versus low-risk groups (10 ± 3.0 ng/ml vs. 4.4 ± 1.2 ng/ml, p = 0.03; 20.6 ± 10.6 ng/ml vs. 4.5 ± 1.4 ng/ml, p = 0.03, respectively). Corresponding serum samples revealed higher levels of MUC5AC in high-risk compared with low-risk patients (19.9 ± 9.3 ng/ml vs. 2.2 ± 1.1 ng/ml, p = 0.04). Histopathologic subtype was significantly associated with grade of dysplasia, and the intestinal subtype displayed increased MUC2 cyst fluid concentrations (13.8 ± 6.5 ng/ml vs. 4.1 ± 0.9 ng/ml, p = 0.02).


CONCLUSIONS
In this study, high-risk IPMN showed elevated cyst fluid concentrations of MUC2 and MUC4, and increased serum levels of MUC5AC. High-risk IPMN also displayed a distinct mucin expression profile in specific histologic subtypes. These data, if validated, may allow surgeons to more appropriately select patients for operative resection.
Maker
Ajay V
AV
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ajaymaker@gmail.com
Katabi
Nora
N
Gonen
Mithat
M
DeMatteo
Ronald P
RP
D'Angelica
Michael I
MI
Fong
Yuman
Y
Jarnagin
William R
WR
Brennan
Murray F
MF
Allen
Peter J
PJ
D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D003560:Cysts / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D055271:Mucin 5AC / Q000378:metabolism; D018396:Mucin-1 / Q000378:metabolism; D055262:Mucin-2 / Q000378:metabolism; D055264:Mucin-4 / Q000378:metabolism; D010180:Pancreatectomy; D010189:Pancreatic Juice / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D011379:Prognosis; D011446:Prospective Studies
D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; C524625:MUC2 protein, human; C524658:MUC4 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D055264:Mucin-4