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The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma.
Clin Cancer Res 2001; 7(12):4115-21CC

Abstract

PURPOSE

SMAD4 (also called Dpc4) is a tumor suppressor in the TGF-beta signaling pathway that is genetically inactivated in approximately 55% of all pancreatic adenocarcinomas. We investigated whether prognosis after surgical resection for invasive pancreatic adenocarcinoma is influenced by SMAD4 status.

EXPERIMENTAL DESIGN

Using immunohistochemistry, we characterized the SMAD4 protein status of 249 pancreatic adenocarcinomas resected from patients who underwent pancreaticoduodenectomy (Whipple resection) at The Johns Hopkins Hospital, Baltimore, MD, between 1990 and 1997. The SMAD4 gene status of 56 of 249 (22%) pancreatic carcinomas was also determined. A multivariate Cox proportional hazards model assessed the relative risk of mortality associated with SMAD4 status, adjusting for known prognostic variables.

RESULTS

Patients with pancreatic adenocarcinomas with SMAD4 protein expression had significantly longer survival (unadjusted median survival was 19.2 months as compared with 14.7 months in patients with pancreatic cancers lacking SMAD4 protein expression; P = 0.03). This SMAD4 survival benefit persisted after adjustment for prognostic factors including tumor size, margins, lymph node status, pathological stage, blood loss, and use of adjuvant chemoradiotherapy. The relative hazard of mortality for cancers lacking SMAD4 after adjusting for other prognostic factors was 1.36 (95% confidence interval, 1.01-1.83; P = 0.04).

CONCLUSION

Patients undergoing Whipple resection for pancreatic adenocarcinoma survive longer if their cancers express SMAD4.

Authors+Show Affiliations

Department of Pathology, The Johns Hopkins University School of Medicine, 632 Ross Building, Baltimore, MD 21205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

11751510

Citation

Tascilar, M, et al. "The SMAD4 Protein and Prognosis of Pancreatic Ductal Adenocarcinoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 7, no. 12, 2001, pp. 4115-21.
Tascilar M, Skinner HG, Rosty C, et al. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2001;7(12):4115-21.
Tascilar, M., Skinner, H. G., Rosty, C., Sohn, T., Wilentz, R. E., Offerhaus, G. J., ... Goggins, M. (2001). The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 7(12), pp. 4115-21.
Tascilar M, et al. The SMAD4 Protein and Prognosis of Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2001;7(12):4115-21. PubMed PMID: 11751510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. AU - Tascilar,M, AU - Skinner,H G, AU - Rosty,C, AU - Sohn,T, AU - Wilentz,R E, AU - Offerhaus,G J, AU - Adsay,V, AU - Abrams,R A, AU - Cameron,J L, AU - Kern,S E, AU - Yeo,C J, AU - Hruban,R H, AU - Goggins,M, PY - 2001/12/26/pubmed PY - 2002/3/28/medline PY - 2001/12/26/entrez SP - 4115 EP - 21 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 7 IS - 12 N2 - PURPOSE: SMAD4 (also called Dpc4) is a tumor suppressor in the TGF-beta signaling pathway that is genetically inactivated in approximately 55% of all pancreatic adenocarcinomas. We investigated whether prognosis after surgical resection for invasive pancreatic adenocarcinoma is influenced by SMAD4 status. EXPERIMENTAL DESIGN: Using immunohistochemistry, we characterized the SMAD4 protein status of 249 pancreatic adenocarcinomas resected from patients who underwent pancreaticoduodenectomy (Whipple resection) at The Johns Hopkins Hospital, Baltimore, MD, between 1990 and 1997. The SMAD4 gene status of 56 of 249 (22%) pancreatic carcinomas was also determined. A multivariate Cox proportional hazards model assessed the relative risk of mortality associated with SMAD4 status, adjusting for known prognostic variables. RESULTS: Patients with pancreatic adenocarcinomas with SMAD4 protein expression had significantly longer survival (unadjusted median survival was 19.2 months as compared with 14.7 months in patients with pancreatic cancers lacking SMAD4 protein expression; P = 0.03). This SMAD4 survival benefit persisted after adjustment for prognostic factors including tumor size, margins, lymph node status, pathological stage, blood loss, and use of adjuvant chemoradiotherapy. The relative hazard of mortality for cancers lacking SMAD4 after adjusting for other prognostic factors was 1.36 (95% confidence interval, 1.01-1.83; P = 0.04). CONCLUSION: Patients undergoing Whipple resection for pancreatic adenocarcinoma survive longer if their cancers express SMAD4. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/11751510/The_SMAD4_protein_and_prognosis_of_pancreatic_ductal_adenocarcinoma_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11751510 DB - PRIME DP - Unbound Medicine ER -