DPC4/Smad4 expression and outcome in pancreatic ductal adenocarcinoma

被引:143
作者
Biankin, AV
Morey, AL
Lee, CS
Kench, JG
Biankin, SA
Hook, HC
Head, DR
Hugh, TB
Sutherland, RL
Henshall, SM
机构
[1] Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia
[2] Westmead Hosp, Inst Clin Pathol & Med Res, Westmead, NSW 2145, Australia
[3] Univ Sydney, Dept Pathol, Camperdown, NSW, Australia
[4] Royal Prince Alfred Hosp, Dept Pathol Anat, Sydney, NSW, Australia
[5] Dept Anat Pathol, Sydney, NSW, Australia
[6] Div Surg, Sydney, NSW, Australia
关键词
D O I
10.1200/JCO.2002.12.063
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Prognostic indicators in pancreatic cancer (PC) are poorly defined and difficult to quantify preoperatively, hence they may lead to inappropriate patient selection for treatment. We examined the protein expression of key cell-cycle regulatory and cell-signaling molecules that occur at high frequency in PC and assessed their relationship to clinicopathologic parameters, response to operative resection, and outcome. Patients and Methods: We identified 348 patients with pancreatic ductal adenocarcinoma and assessed the influence of reported clinicopathologic prognostic factors and the expression of the cell-cycle regulatory genes p21(WAF1/CIP1) (CDKN1A), cyclin D1 (CCND1), p53, and p16(INK4A) (CDKN2) and the cell-signaling molecule DPC4/Smad4 (MADH4) using immunohistochemistry in a subgroup of 129 patients. Results: Independent prognostic factors in resected patients were tumor size greater than 45 mm (P = .0015), involvement of surgical margins (P < .0001), and perineural invasion (P = .014). Loss of DPC4/Smad4 expression cosegregated with resectability (P < .0001) and was associated with improved survival after resection (P < .0001), whereas resection did not improve survival in patients whose tumor expressed DPC4/Smad4 (P = .5). Aberrant expression of p21(WAF1/CIP1), cyclin D1, p53, or p16(INK4A) was not associated with a difference in survival. Conclusion: Tumor size (> 45 mm), resection margin involvement, and perineural invasion were independent prognostic factors. Preoperative assessment of DPC4/Smad4 expression has potential as a prognostic indicator in patients with PC since resection did not benefit those patients whose cancers expressed DPC4/Smad4 and accurate assessment of DPC4/Smad4 expression, unlike tumor size, margin status, and perineural invasion, does not require resection. (C) 2002 by American Society of Clinical Oncology.
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页码:4531 / 4542
页数:12
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