Failure patterns in resected pancreas adenocarcinoma: Lack of predicted benefit to SMAD4 expression Journal Article


Authors: Winter, J. M.; Tang, L. H.; Klimstra, D. S.; Liu, W.; Linkov, I.; Brennan, M. F.; D'Angelica, M. I.; DeMatteo, R. P.; Fong, Y.; Jarnagin, W. R.; O'Reilly, E. M.; Allen, P. J.
Article Title: Failure patterns in resected pancreas adenocarcinoma: Lack of predicted benefit to SMAD4 expression
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. Copyright © 2013 Lippincott Williams & Wilkins.
Keywords: immunohistochemistry; cancer survival; human tissue; protein expression; treatment outcome; disease-free survival; survival rate; treatment failure; major clinical study; cancer recurrence; cancer adjuvant therapy; pancreas cancer; pancreas resection; pancreatic neoplasms; follow up; follow-up studies; lymph node metastasis; antineoplastic agent; pancreaticoduodenectomy; pancreas; neoplasm recurrence, local; logistic models; carcinoma, pancreatic ductal; tumor markers, biological; medical record review; retrospective study; distant metastasis; lung metastasis; death; cancer specific survival; pancreas adenocarcinoma; pancreatectomy; tissue array analysis; multivariate analysis; tissue microarray; distal pancreatectomy; smad4 protein; recurrence pattern; smad4
Journal Title: Annals of Surgery
Volume: 258
Issue: 2
ISSN: 0003-4932
Publisher: Lippincott Williams & Wilkins  
Date Published: 2013-08-01
Start Page: 331
End Page: 335
Language: English
DOI: 10.1097/SLA.0b013e31827fe9ce
PROVIDER: scopus
PUBMED: 23360922
PMCID: PMC4431700
DOI/URL:
Notes: - "Export Date: 1 August 2013" - "CODEN: ANSUA" - "Source: Scopus"
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MSK Authors
  1. Murray F Brennan
    1059 Brennan
  2. Ronald P DeMatteo
    637 DeMatteo
  3. David S Klimstra
    978 Klimstra
  4. Peter Allen
    501 Allen
  5. William R Jarnagin
    903 Jarnagin
  6. Yuman Fong
    775 Fong
  7. Laura Hong Tang
    447 Tang
  8. Eileen O'Reilly
    780 O'Reilly
  9. Weiguo Liu
    6 Liu
  10. Irina Linkov
    73 Linkov