Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Aug;258(2):331-5.
doi: 10.1097/SLA.0b013e31827fe9ce.

Failure patterns in resected pancreas adenocarcinoma: lack of predicted benefit to SMAD4 expression

Jordan M Winter  1 , Laura H Tang, David S Klimstra, Weiguo Liu, Irena Linkov, Murray F Brennan, Michael I DʼAngelica, Ronald P DeMatteo, Yuman Fong, William R Jarnagin, Eileen M Oʼreilly, Peter J Allen
Affiliations

Failure patterns in resected pancreas adenocarcinoma: lack of predicted benefit to SMAD4 expression

Jordan M Winter et al. Ann Surg. 2013 Aug.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
SMAD4 immunohistochemistry in representative cores of pancreatic ductal adenocarcinoma. Neoplastic epithelial cells lack SMAD4 expression in contrast to nonneoplastic stromal cells in a) and b). SMAD4 expression is observed in cancer cells as well as the non-neoplastic stromal cells in c) and d).
Figure 2
Figure 2
Percentage of patients (total, n=127) who recurred at the indicated sites. NED, no evidence of disease.
See this image and copyright information in PMC

References

    1. Varadhachary GR, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine- based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487–95. - PubMed
    1. Conroy T, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25. - PubMed
    1. Jones S, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–6. - PMC - PubMed
    1. Latil A, et al. Gene expression profiling in clinically localized prostate cancer: a four-gene expression model predicts clinical behavior. Clin Cancer Res. 2003;9(15):5477–85. - PubMed
    1. Yachida S, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467(7319):1114–7. - PMC - PubMed

Publication types

MeSH terms