Failure patterns in resected pancreas adenocarcinoma: lack of predicted benefit to SMAD4 expression.
OBJECTIVE
To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA).


BACKGROUND
SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection.


METHODS
A tissue microarray was constructed including 127 patients with resected PDA and either short-term (<12 months) or long-term (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes (eg, recurrence pattern and early cancer-specific mortality) were determined.


RESULTS
Loss of SMAD4 expression in pancreatic adenocarcinoma was identified in 40 of 127 patients (32%). SMAD4 loss occurred in 27% of patients who experienced isolated local recurrence, 33% of patients with a distant recurrence, 33% of patients who experienced local and distant site recurrences, and 25% of patients who were without evidence of recurrence (Fisher exact, P = 0.9). In a multivariate analysis, the presence of regional lymph node metastases was the only factor associated with the development of distant metastases (odds ratio = 4.7, P = 0.02). SMAD4 was neither associated with recurrence pattern (odds ratio = 0.9, P = 0.9) nor associated with early death (odds ratio = 0.5, P = 0.15).


CONCLUSIONS
Primary tumor SMAD4 expression status was not a predictor of recurrence pattern in a large cohort of patients with resected PDA.
Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
Jordan M
JM
Winter
Laura H
LH
Tang
David S
DS
Klimstra
Weiguo
W
Liu
Irena
I
Linkov
Murray F
MF
Brennan
Michael I
MI
DʼAngelica
Ronald P
RP
DeMatteo
Yuman
Y
Fong
William R
WR
Jarnagin
Eileen M
EM
Oʼreilly
Peter J
PJ
Allen
D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016577:Pancreaticoduodenectomy; D051901:Smad4 Protein / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C497796:SMAD4 protein, human; D051901:Smad4 Protein