Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer

British Journal of Cancer

Volumn 104, Issue 9, 2011, Pages 1440-1451

  Smith, R A ^a   Tang, J ^a   Tudur Smith, C ^a   Neoptolemos, J P ^a   Ghaneh, P ^a  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

immunohistochemistry; meta analysis; molecular; pancreatic cancer; prognosis

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P16; VASCULOTROPIN;

ARTICLE; CANCER SURGERY; CANCER SURVIVAL; HUMAN; IMMUNOHISTOCHEMISTRY; OVERALL SURVIVAL; PANCREAS CANCER; PRIORITY JOURNAL; PROGNOSIS; SYSTEMATIC REVIEW;

ADENOCARCINOMA; BCL-2-ASSOCIATED X PROTEIN; HUMANS; IMMUNOHISTOCHEMISTRY; NEOPLASM PROTEINS; PANCREATIC NEOPLASMS; PREDICTIVE VALUE OF TESTS; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-BCL-2; RECEPTOR, EPIDERMAL GROWTH FACTOR; SMAD4 PROTEIN; TUMOR MARKERS, BIOLOGICAL; TUMOR SUPPRESSOR PROTEIN P53; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 79955472083     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2011.110     Document Type: Article

References (122)

1. Achen MG, Stacker SA (2008) Molecular control of lymphatic metastasis. Ann N Y Acad Sci 1131: 225-234 (Pubitemid 351758517)
2. Ahrendt SA, Brown HM, Komorowski RA, Zhu YR, Wilson SD, Erickson BA, Ritch PS, Pitt HA, Demeure MJ (2000) p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer. Surgery 128: 520-530
3. Ai KX, Lu LY, Huang XY, Chen W, Zhang HZ (2008) Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer. World J Gastroenterol 14: 1931-1935 (Pubitemid 351523827)
4. Aizawa S, Sasaki M, Wada R, Koyama M, Yagihashi S (1996) P53 protein expression in pancreatic tumors and its relationship to clinicopatholo-gical factors and prognosis. J Surg Oncol 62: 279-283 (Pubitemid 26262352)
5. Altman DG (2001) Systematic reviews of evaluations of prognostic variables. BMJ 323: 224-228
6. Bergan A, Gladhaug IP, Schjolberg A, Bergan AB, Clausen OP (2000) p53 accumulation confers prognostic information in resectable adeno-carcinomas with ductal but not with intestinal differentiation in the pancreatic head. Int J Oncol 17: 921-926
7. Biankin AV, Morey AL, Lee CS, Kench JG, Biankin SA, Hook HC, Head DR, Hugh TB, Sutherland RL, Henshall SM (2002) DPC4/Smad4 expression and outcome in pancreatic ductal adenocarcinoma. J Clin Oncol 20: 4531-4542 (Pubitemid 35402956)
8. Bloomston M, Bhardwaj A, Ellison EC, Frankel WL (2006) Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg 23: 74-79 (Pubitemid 44174844)
9. Bold RJ, Hess KR, Pearson AS, Grau AM, Sinicrope FA, Jennings M, McConkey DJ, Bucana CD, Cleary KR, Hallin PA, Chiao PJ, Abbruzzese JL, Evans DB (1999) Prognostic factors in resectable pancreatic cancer: p53 and bcl-2. J Gastrointest Surg 3: 263-277
10. Büchler P, Reber HA, Büchler MW, Friess H, Hines OJ (2002) VEGF-RII influences the prognosis of pancreatic cancer. Ann Surg 236: 738-749 (Pubitemid 35403229)
11. Callagy GM, Webber MJ, Pharoah PD, Caldas C (2008) Meta-analysis confirms bcl-2 is an independent prognostic marker in breast cancer. BMC Cancer 8: 153
12. Campani D, Boggi U, Cecchetti D, Esposito I, Ceccarelli F, D'Antonio L, De Negri F, Mosca F, Bevilacqua G, Fornaciari G (1999) p53 over-expression in lymph node metastases predicts clinical outcome in ductal pancreatic cancer. Pancreas 19: 26-32 (Pubitemid 29293505)
13. Campani D, Esposito I, Boggi U, Cecchetti D, Menicagli M, De Negri F, Colizzi L, Del Chiaro M, Mosca F, Fornaciari G, Bevilacqua G (2001) Bcl-2 expression in pancreas development and pancreatic cancer progression. J Pathol 194: 444-450 (Pubitemid 32782669)
14. Chung GG, Yoon HH, Zerkowski MP, Ghosh S, Thomas L, Harigopal M, Charette LA, Salem RR, Camp RL, Rimm DL, Burtness BA (2006) Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray. Cancer 106: 1677-1684
15. Ciardello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358: 1160-1174
16. Coppola D, Lu L, Fruehauf JP, Kyshtoobayeva A, Karl RC, Nicosia SV, Yeatman TJ (1998) Analysis of p53, p21WAF1, and TGF-beta1 in human ductal adenocarcinoma of the pancreas: TGF-beta1 protein expression predicts longer survival. Am J Clin Pathol 110: 16-23 (Pubitemid 28294730)
17. Dallas NA, Fan F, Gray MJ, Van Buren II G, Lim SJ, Xia L, Ellis LM (2007) Functional significance of vascular endothelial growth factor receptors on gastrointestinal cancer cells. Cancer Metastasis Rev 26: 433-441 (Pubitemid 350115100)
18. Dang CX, Han Y, Qin ZY, Wang YJ (2002) Clinical significance of expression of p21 and p53 proteins and proliferating cell nuclear antigen in pancreatic cancer. Hepatobiliary Pancreat Dis Int 1: 302-305 (Pubitemid 36748225)
19. Delmotte P, Martin B, Paesmans M, Berghmans T, Mascaux C, Meert AP, Steels E, Verdebout JM, Lafitte JJ, Sculier JP (2002) VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis. Rev Mal Respir 19: 577-584 (Pubitemid 35303646)
20. Dergham ST, Dugan MC, Joshi US, Chen YC, Du W, Smith DW, Arlauskas P, Crissman JD, Vaitkevicius VK, Sarkar FH (1997a) The clinical significance of p21(WAF1/CIP-1) and p53 expression in pancreatic adenocarcinoma. Cancer 80: 372-381
21. Dergham ST, Dugan MC, Kucway R, Du W, Kamarauskiene DS, Vaitkevicius VK, Crissman JD, Sarkar FH (1997b) Prevalence and clinical significance of combined K-ras mutation and p53 aberration in pancreatic adenocarcinoma. Int J Pancreatol 21: 127-143 (Pubitemid 27278611)
22. Dergham ST, Dugan MC, Sarkar FH, Vaitkevicius VK (1998) Molecular alterations associated with improved survival in pancreatic cancer patients treated with radiation or chemotherapy. J Hepatobiliary Pancreat Surg 5: 269-272 (Pubitemid 128662592)
23. Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, Breau JL, Perret GY (2006) Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 94: 1823-1832 (Pubitemid 43882572)
24. DiGiuseppe JA, Hruban RH, Goodman SN, Polak M, van den Berg FM, Allison DC, Cameron JL, Offerhaus GJ (1994) Overexpression of p53 protein in adenocarcinoma of the pancreas. Am J Clin Pathol 101: 684-688 (Pubitemid 24169297)
25. Dong M, Dong Q, Zhang H, Zhou J, Tian Y, Dong Y (2007) Expression of Gadd45a and p53 proteins in human pancreatic cancer: potential effects on clinical outcomes. J Surg Oncol 95: 332-336 (Pubitemid 46355510)
26. Dong M, Ma G, Tu W, Guo KJ, Tian YL, Dong YT (2005a) Clinicopatho-logical significance of p53 and mdm2 protein expression in human pancreatic cancer. World J Gastroenterol 11: 2162-2165 (Pubitemid 40542663)
27. Dong M, Nio Y, Guo KJ, Tamura K, Tian YL, Dong YT (1998a) Epidermal growth factor and its receptor as prognostic indicators in Chinese patients with pancreatic cancer. Anticancer Res 18: 4613-4619 (Pubitemid 29042032)
28. Dong M, Nio Y, Sato Y, Tamura K, Song MM, Tian YL, Dong YT (1998b) Comparative study of p53 expression in primary invasive ductal carcinoma of the pancreas between Chinese and Japanese. Pancreas 17: 229-237 (Pubitemid 28455707)
29. Dong M, Nio Y, Tamura K, Song MM, Guo KJ, Guo RX, Dong YT (2000) Ki-ras point mutation and p53 expression in human pancreatic cancer: a comparative study among Chinese, Japanese, and Western patients. Cancer Epidemiol Biomarkers Prev 9: 279-284 (Pubitemid 30165440)
30. Dong M, Nio Y, Yamasawa K, Toga T, Yue L, Harada T (2003) p53 alteration is not an independent prognostic indicator, but affects the efficacy of adjuvant chemotherapy in human pancreatic cancer. J Surg Oncol 82: 111-120 (Pubitemid 36164446)
31. Dong M, Zhou JP, Zhang H, Guo KJ, Tian YL, Dong YT (2005b) Clinicopathological significance of Bcl-2 and Bax protein expression in human pancreatic cancer. World J Gastroenterol 11: 2744-2747 (Pubitemid 40704240)
32. Ellis LM, Takahashi Y, Fenoglio CJ, Cleary KR, Bucana CD, Evans DB (1998) Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma. Eur J Cancer 34: 337-340 (Pubitemid 28183830)
33. Evans JD, Cornford PA, Dodson A, Greenhalf W, Foster CS, Neoptolemos JP (2001) Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas. Pancreatology 1: 254-262 (Pubitemid 33674930)
34. Farrell JJ, Elsaleh H, Garcia M, Lai R, Ammar A, Regine WF, Abrams R, Benson AB, Macdonald J, Cass CE, Dicker AF, Mackey JR (2009) Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology 136(1): 187-195
35. Friess H, Lu Z, Graber HU, Zimmermann A, Adler G, Korc M, Schmid RM, Büchler MW (1998) bax, but not bcl-2, influences the prognosis of human pancreatic cancer. Gut 43: 414-421 (Pubitemid 28414925)
36. Fujimoto K, Hosotani R, Wada M, Lee JU, Koshiba T, Miyamoto Y, Tsuji S, Nakajima S, Doi R, Imamura M (1998) Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothe-lial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis. Eur J Cancer 34: 1439-1447 (Pubitemid 28370938)
37. Fujioka S, Yoshida K, Yanagisawa S, Kawakami M, Aoki T, Yamazaki Y (2001) Angiogenesis in pancreatic carcinoma: thymidine phosphorylase expression in stromal cells and intratumoral microvessel density as independent predictors of overall and relapse-free survival. Cancer 92: 1788-1797 (Pubitemid 32952497)
38. Gansauge F, Gansauge S, Link KH, Beger HG (1999) p53 in relation to therapeutic outcome of locoregional chemotherapy in pancreatic cancer. Ann N Y Acad Sci 880: 281-287 (Pubitemid 29349136)
39. Gansauge F, Gansauge S, Schmidt E, Müller J, Beger HG (1998) Prognostic significance of molecular alterations in human pancreatic carcinoma - an immunohistological study. Langenbecks Arch Surg 383: 152-155 (Pubitemid 28442529)
40. Gazzaniga GM, Papadia FS, Dezzana M, Cappato S, Filauro M, Bandelloni R (2001) Role of p53 mutations on survival after pancreatoduodenectomy for ductal adenocarcinoma of the pancreatic head. Hepatogastroenter-ology 48: 1743-1745 (Pubitemid 34003517)
41. Gerdes B, Ramaswamy A, Ziegler A, Lang SA, Kersting M, Baumann R, Wild A, Moll R, Rothmund M, Bartsch DK (2002) p16INK4a is a prognostic marker in resected ductal pancreatic cancer: an analysis of p16INK4a, p53, MDM2, an Rb. Ann Surg 235: 51-59 (Pubitemid 34062399)
42. Hamacher R, Schmid RM, Saur D, Schneider G (2008) Apoptotic pathways in pancreatic ductal adenocarcinoma. Mol Cancer 7: 64
43. Hashimoto K, Nio Y, Koike M, Itakura M, Yano S, Higami T, Maruyama R (2005) Expression of retinoblastoma and p53 pathway-related proteins in resectable invasive ductal carcinoma of the pancreas: potential cooperative effects on clinical outcome. Anticancer Res 25: 1361-1368 (Pubitemid 40546816)
44. Hayden JA, Côté P, Bombardier C (2006) Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med 144: 427-437 (Pubitemid 46768164)
45. Hermanova M, Karasek P, Nenuti R, Kyr M, Tomasek J, Baltasova I, Dite P (2009) Clinicopathological correlations of cyclooxygenase-2, MDM2, and p53 expressions in surgically resectable pancreatic invasive ductal adenocarcinoma. Pancreas 38: 565-571
46. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21: 1539-1558 (Pubitemid 34746062)
47. Hu YX, Watanabe H, Ohtsubo K, Yamaguchi Y, Ha A, Motoo Y, Okai T, Sawabu N (1999) Bcl-2 expression related to altered p53 protein and its impact on the progression of human pancreatic carcinoma. Br J Cancer 80: 1075-1079 (Pubitemid 29233932)
48. Hu YX, Watanabe H, Ohtsubo K, Yamaguchi Y, Ha A, Okai T, Sawabu N (1997) Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma. Clin Cancer Res 3: 1473-1477 (Pubitemid 27431553)
49. Hua Z, Zhang YC, Hu XM, Jia ZG (2003) Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma. World J Gastroenterol 9: 2764-2767 (Pubitemid 38054456)
50. Ikeda N, Adachi M, Taki T, Huang C, Hashida H, Takabayashi A, Sho M, Nakajima Y, Kanehiro H, Hisanaga M, Nakano H, Miyake M (1999) Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer 79: 1553-1563 (Pubitemid 29116820)
51. Ikeda N, Nakajima Y, Sho M, Adachi M, Huang CL, Iki K, Kanehiro H, Hisanaga M, Nakano H, Miyake M (2001) The association of K-ras gene mutation and vascular endothelial growth factor gene expression in pancreatic carcinoma. Cancer 92: 488-499 (Pubitemid 32735183)
52. Itakura J, Ishiwata T, Friess H, Fujii H, Matsumoto Y, Büchler MW, Korc M (1997) Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clin Cancer Res 3: 1309-1316 (Pubitemid 27362391)
53. Jeong J, Park YN, Park JS, Yoon DS, Chi HS, Kim BR (2005) Clinical significance of p16 protein expression loss and aberrant p53 protein expression in pancreatic cancer. Yonsei Med J 46: 519-525 (Pubitemid 41283063)
54. Jinfeng M, Kimura W, Sakurai F, Moriya T, Mizutani M, Hirai I (2007) Prognostic role of angiogenesis and its correlations with thymidine phosphorylase and p53 expression in ductal adenocarcinoma of the pancreas. Hepatogastroenterology 54: 1635-1640 (Pubitemid 350068442)
55. Karademir S, Sökmen S, Terzi C, Sag?ol O, Ozer E, Astarciog?lu H, Coker A, Astarciog?lu I (2000) Tumor angiogenesis as a prognostic predictor in pancreatic cancer. J Hepatobiliary Pancreat Surg 7: 489-495
56. Kawesha A, Ghaneh P, Andrén-Sandberg A, Ograed D, Skar R, Dawiskiba S, Evans JD, Campbell F, Lemoine N, Neoptolemos JP (2000) K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma. Int J Cancer 89: 469-474
57. Khorana AA, Hu YC, Ryan CK, Komorowski RA, Hostetter G, Ahrendt SA (2005) Vascular endothelial growth factor and DPC4 predict adjuvant therapy outcomes in resected pancreatic cancer. J Gastrointest Surg 9: 903-911 (Pubitemid 41224283)
58. Knoll MR, Rudnitzki D, Sturm J, Manegold BC, Post S, Jaeger TM (2001) Correlation of postoperative survival and angiogenic growth factors in pancreatic carcinoma. Hepatogastroenterology 48: 1162-1165 (Pubitemid 32757767)
59. Kurahara H, Takao S, Maemura K, Shinchi H, Natsugoe S, Aikou T (2004) Impact of vascular endothelial growth factor-C and -D expression in human pancreatic cancer: its relationship to lymph node metastasis. Clin Cancer Res 10: 8413-8420 (Pubitemid 40053404)
60. Kuwahara K, Sasaki T, Kuwada Y, Murakami M, Yamasaki S, Chayama K (2003) Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas 26: 344-349 (Pubitemid 36529959)
61. Kyzas PA, Cunha IW, Ioannidis JP (2005a) Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res 11: 1434-1440 (Pubitemid 40315223)
62. Kyzas PA, Loizou KT, Ioannidis JP (2005b) Selective reporting biases in cancer prognostic factor studies. J Natl Cancer Inst 97: 1043-1055 (Pubitemid 41417921)
63. Lee EU, Cibull ML, O'Daniel-Pierce E, Strodel WE, Jennings CD (1995) Expression of p53 protein in pancreatic adenocarcinoma. Relationship to cigaret smoking. Int J Pancreatol 17: 237-242
64. Li Y, Bhuiyan M, Vaitkevicius VK, Sarkar FH (1999) Structural alteration of p53 protein correlated to survival in patients with pancreatic adeno-carcinoma. Pancreas 18: 104-110 (Pubitemid 29011343)
65. Lim YJ, Lee JK, Park CK, Song SY, Jang WY, Ha HY, Park DI, Lee KT, Paik SW, Yoo BC, Rhee JC (2004) Prognostic value of VEGF in human pancreatic ductal adenocarcinoma. Korean J Intern Med 19: 10-14 (Pubitemid 41237482)
66. Linder S, Bla?sjö M, von Rosen A, Parrado C, Falkmer UG, Falkmer S (2001) Pattern of distribution and prognostic value of angiogenesis in pancreatic duct carcinoma: a semiquantitative immunohistochemical study of 45 patients. Pancreas 22: 240-247 (Pubitemid 32242488)
67. Linder S, Parrado C, Falkmer UG, Bla?sjö M, Sundelin P, von Rosen A (1997) Prognostic significance of Ki-67 antigen and p53 protein expression in pancreatic duct carcinoma: a study of the monoclonal antibodies MIB-1 and DO-7 in formalin-fixed paraffin-embedded tumour material. Br J Cancer 76: 54-59 (Pubitemid 27250076)
68. Lundin J, Nordling S, von Boguslawsky K, Roberts PJ, Haglund C (1996) Prognostic value of immunohistochemical expression of p53 in patients with pancreatic cancer. Oncology 53: 104-111 (Pubitemid 26087917)
69. Magistrelli P, Coppola R, Tonini G, Vincenzi B, Santini D, Borzomati D, Vecchio F, Valeri S, Castri F, Antinori A, Nuzzo G, Caraglia M, Picciocchi A (2006) Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma. J Cell Biochem 97: 98-108 (Pubitemid 43050182)
70. Mäkinen K, Hakala T, Lipponen P, Alhava E, Eskelinen M (1998) Clinical contribution of bcl-2, p53 and Ki-67 proteins in pancreatic ductal adenocarcinoma. Anticancer Res 18: 615-658
71. Malats N, Bustos A, Nascimento CM, Fernandez F, Rivas M, Puente D, Kogevinas M, Real FX (2005) P53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol 6: 678-686 (Pubitemid 41222758)
72. Manuyakorn A, Paulus R, Farrell J, Dawson NA, Tze S, Cheung-Lau G, Hines OJ, Reber H, Seligson DB, Horvath S, Kurdistani SK, Dawson DW (2010) Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704. J Clin Oncol 28: 1358-1365
73. Martin B, Paesmans M, Berghmans T, Branle F, Ghisdal L, Mascaux C, Meert AP, Steels E, Vallot F, Verdebout JM, Lafitte JJ, Sculier JP (2003) Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 89: 55-64 (Pubitemid 36897935)
74. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2006) Reporting recommendations for tumor marker prognostic studies (REMARK). Exp Oncol 28: 99-105 (Pubitemid 44140259)
75. Naka T, Kobayashi M, Ashida K, Toyota N, Kaneko T, Kaibara N (1998) Aberrant p16INK4 expression related to clinical stage and prognosis in patients with pancreatic cancer. Int J Oncol 12: 1111-1116
76. Nash AD, Baca M, Wright C, Scotney PD (2006) The biology of vascular endothelial growth factor-B (VEGF-B). Pulm Pharmacol Ther 19: 61-69 (Pubitemid 41606854)
77. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW, European Study Group for Pancreatic Cancer (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350: 1200-1210 (Pubitemid 38339364)
78. Niedergethmann M, Hildenbrand R, Wolf G, Verbeke CS, Richter A, Post S (2000) Angiogenesis and cathepsin expression are prognostic factors in pancreatic adenocarcinoma after curative resection. Int J Pancreatol 28: 31-39
79. Niedergethmann M, Hildenbrand R, Wostbrock B, Hartel M, Sturm JW, Richter A, Post S (2002) High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas. Pancreas 25: 122-129 (Pubitemid 34815907)
80. Nio Y, Dong M, Uegaki K, Hirahara N, Minari Y, Sasaki S, Takamura M, Iguchi C, Tamura K (1998) p53 expression affects the efficacy of adjuvant chemotherapy after resection of invasive ductal carcinoma of the pancreas. Anticancer Res 18: 3773-3779 (Pubitemid 28564264)
81. Nio Y, Dong M, Uegaki K, Hirahara N, Minari Y, Sasaki S, Takamura M, Iguchi C, Tamura K (1999) Comparative significance of p53 and WAF/1-p21 expression on the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma of the pancreas. Pancreas 18: 117-126 (Pubitemid 29180107)
82. Nio Y, Dong M, Iguchi C, Yamasawa K, Toga T, Itakura M, Tamura K (2001a) Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: effects on clinical outcome and efficacy of adjuvant chemotherapy. J Surg Oncol 76: 188-196 (Pubitemid 32240229)
83. Nio Y, Iguchi C, Yamasawa K, Sasaki S, Takamura M, Toga T, Dong M, Itakura M, Tamura K (2001b) Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas. Pancreas 22: 230-239 (Pubitemid 32242487)
84. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297: 267-277 (Pubitemid 46143304)
85. Ohshio G, Suwa H, Imamura M (2002) Clinical implication of anti-p53 antibodies and p53-protein in pancreatic disease. Int J Gastrointest Cancer 31: 129-135 (Pubitemid 36330115)
86. Ohshio G, Suwa H, Imamura T, Yamaki K, Tanaka T, Hashimoto Y, Imamura M (1998) An immunohistochemical study of bcl-2 and p53 protein expression in pancreatic carcinomas. Scand J Gastroenterol 33: 535-539 (Pubitemid 28277255)
87. Ohtsubo K, Watanabe H, Yamaguchi Y, Hu YX, Motoo Y, Okai T, Sawabu N (2003) Abnormalities of tumor suppressor gene p16 in pancreatic carcinoma: immunohistochemical and genetic findings compared with clinicopathological parameters. J Gastroenterol 38: 663-671 (Pubitemid 36974980)
88. Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival end-points. Stat Med 17: 2815-2834 (Pubitemid 28562978)
89. Riall TS, Cameron JL, Lillemoe KD, Winter JM, Campbell KA, Hruban RH, Chang D, Yeo CJ (2006) Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up. Surgery 140: 764-772 (Pubitemid 44648193)
90. Sarela AI, Verbeke CS, Ramsdale J, Davies CL, Markham AF, Guillou PJ (2002) Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma. Br J Cancer 86: 886-892 (Pubitemid 34271023)
91. Sato Y, Nio Y, Song MM, Sumi S, Hirahara N, Minari Y, Tamura K (1997) p53 protein expression as prognostic factor in human pancreatic cancer. Anticancer Res 17: 2779-2788 (Pubitemid 27352687)
92. Schutte M, Hruban RH, Geradts J (1997) Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res 57: 3126-3130 (Pubitemid 27351723)
93. Seo Y, Baba H, Fukuda T, Takashima M, Sugimachi K (2000) High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer 88: 2239-2245 (Pubitemid 30247122)
94. Sessa F, Bonato M, Bisoni D, Ranzani GN, Capella C (1998) Ki-ras and p53 gene mutations in pancreatic ductal carcinoma: a relationship with tumor phenotype and survival. Eur J Histochem 42: 67-76 (Pubitemid 29096896)
95. Sinicrope FA, Evans DB, Leach SD, Cleary KR, Fenoglio CJ, Lee JJ, Abbruzzese JL (1996) bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome. Clin Cancer Res 2: 2015-2022 (Pubitemid 27006634)
96. Smeenk HG, Erdmann J, van Dekken H, van Marion R, Hop WC, Jeekel J, van Eijck CH (2007) Long-term survival after radical resection for pancreatic head and ampullary cancer: a potential role for the EGF-R. Dig Surg 24: 38-45 (Pubitemid 46625213)
97. Stipa F, Lucandri G, Limiti MR, Bartolucci P, Cavallini M, Di Carlo V, D'Amato A, Ribotta G, Stipa S (2002) Angiogenesis as a prognostic indicator in pancreatic ductal adenocarcinoma. Anticancer Res 22: 445-449 (Pubitemid 34475337)
98. Sun CY, Wang BL, Hu CQ, Peng RY, Gao YB, Gu QY, Wang DW (2002) Expression of the bcl-2 gene and its significance in human pancreatic carcinoma. Hepatobiliary Pancreat Dis Int 1: 306-308
99. Takikita M, Altekruse S, Lynch CF, Goodman MT, Hermandez BY, Green M, Cozen W, Cockburn M, Siburg Saber M, Topor M, Zeruto C, Abedi-Ardekani B, Reichman ME, Hewitt SM (2009) Associations between selected biomarkers and prognosis in a population-based pancreatic cancer tissue microarray. Cancer Res 69: 2950-2955
100. Tascilar M, Skinner HG, Rosty C, Sohn T, Wilentz RE, Offerhaus GJ, Adsay V, Abrams RA, Cameron JL, Kern SE, Yeo CJ, Hruban RH, Goggins M (2001) The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res 7: 4115-4121 (Pubitemid 34044636)
101. Tang RF, Itakura J, Aikawa T, Matsuda K, Fujii H, Korc M, Matsumoto Y (2001) Overexpression of lymphangiogenic growth factor VEGF-C in human pancreatic cancer. Pancreas 22: 285-292 (Pubitemid 32242495)
102. Tang RF, Wang SX, Peng L, Wang SX, Zhang M, Li ZF, Zhang ZM, Xiao Y, Zhang FR (2006) Expression of vascular endothelial growth factors A and C in human pancreatic cancer. World J Gastroenterol 12: 280-286 (Pubitemid 43336928)
103. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8: 16
104. Toga T, Nio Y, Hashimoto K, Higami T, Maruyama R (2004) The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome. Anticancer Res 24: 1173-1178 (Pubitemid 38624958)
105. Tomazic A, Pegan V, Ferlan-Marolt K, Pleskovic A, Luzar B (2004) Cyclin D1 and bax influence the prognosis after pancreatoduodenec-tomy for periampullary adenocarcinoma. Hepatogastroenterology 51: 1832-1837 (Pubitemid 39389791)
106. Ueda S, Hatsuse K, Tsuda H, Ogata S, Kawarabayashi N, Takigawa T, Einama T, Morita D, Fukatsu K, Sugiura Y, Matsubara O, Mochizuki H (2006) Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer. Mod Pathol 19: 788-796 (Pubitemid 43780448)
107. Ueda S, Ogata S, Tsuda H, Kawarabayashi N, Kimura M, Sugiura Y, Tamai S, Matsubara O, Hatsuse K, Mochizuki H (2004) The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas 29: 1-8
108. Uegaki K, Nio Y, Inoue Y, Minari Y, Sato Y, Song MM, Dong M, Tamura K (1997) Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer. Anticancer Res 17: 3841-3847 (Pubitemid 28014948)
109. Virkajärvi N, Pääkkö P, Soini Y (1997) Association between p53 overexpression, cell proliferation, tumor necrosis and extent of apoptosis in operated pancreatic adenocarcinoma. APMIS 105: 765-772 (Pubitemid 27450508)
110. Westphal S, Kalthoff H (2003) Apoptosis: targets in pancreatic cancer. Mol Cancer 2: 6
111. Weyrer K, Feichtinger H, Haun M, Weiss G, Ofrer D, Weger AR, Umlauft F, Grunewald K (1996) p53, Ki-ras, and DNA ploidy in human pancreatic ductal adenocarcinoma. Lab Invest 74: 279-289 (Pubitemid 26041029)
112. Wilentz RE, Iacobuzio-Donahue CA, Argani P (2000) Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res 60: 2002-2006 (Pubitemid 30207663)
113. Williamson PR, Smith CT, Hutton JL, Marson AG (2002) Aggregate data meta-analysis with time-to-event outcomes. Stat Med 21: 3337-3351 (Pubitemid 35314654)
114. Yamaguchi K, Chijiiwa K, Torato N, Kinoshita M, Tanaka M (2000) Ki-ras codon 12 point and P53 mutations: a molecular examination of the main tumor, liver, portal vein, peripheral arterial blood and para-aortic lymph node in pancreatic cancer. Am J Gastroenterol 95: 1939-1945 (Pubitemid 30629290)
115. Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M (1993) Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 13: 565-569
116. Yamasawa K, Nio Y, Dong M, Yamaguchi K, Itakura M (2002) Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer. Clin Cancer Res 8: 2563-2569 (Pubitemid 34856340)
117. Yamazaki Y, Morita T (2006) Molecular and functional diversity of vascular endothelial growth factors. Mol Divers 10: 515-527 (Pubitemid 44885229)
118. Yokoyama M, Yamanaka Y, Friess H, Buchler M, Korc M (1994) p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness. Anticancer Res 14: 2477-2483
119. Yu G, Zhu MH, Zhu Z, Ni CR, Zheng JM, Li FM (2004) Expression of ATM protein and its relationship with p53 in pancreatic carcinoma with tissue array. Pancreas 28: 421-426 (Pubitemid 38509747)
120. Zhang SY, Ruggeri B, Agarwal P, Sorling AF, Obara T, Ura H, Namiki M, Klein-Szanto AJ (1994) Immunohistochemical analysis of p53 expression in human pancreatic carcinomas. Arch Pathol Lab Med 118: 150-154 (Pubitemid 24046474)
121. Zhang B, Zhao WH, Zhou WY, Yu WS, Yu JM, Li S (2007) Expression of vascular endothelial growth factors-C and -D correlate with evidence of lymphangiogenesis and angiogenesis in pancreatic adenocarcinoma. Cancer Detect Prev 31: 436-442 (Pubitemid 350181738)
122. Zhang L, Yuan SZ (2002) Expression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-beta1 in human pancreatic ductal adenocarcinoma. Hepatobiliary Pancreat Dis Int 1: 620-623 (Pubitemid 36748255)