Prognostic Significance of p53 in Gastric Cancer: a Meta-Analysis

  • Yildirim, Mustafa (Department of Medical Oncology, Ministry of Health Batman Regional Government Hospital) ;
  • Kaya, Vildan (Department of Radiation Oncology, Medical Faculty, Suleyman Demirel University) ;
  • Demirpence, Ozlem (Department of Biochemistry, Ministry of Health Batman Regional Government Hospital) ;
  • Gunduz, Seyda (Antalya Education and Research Hospital) ;
  • Bozcuk, Hakan (Department of Medical Oncology, Medical Faculty, Akdeniz University)
  • Published : 2015.02.04


Background: Gastric cancer is one of the frequently seen cancers in the world and it is the second most common reason for death due to cancer. The prognostic role of expression of p53 detected by immunohistochemistry in gastric cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. Materials and Methods: We systematically searched for studies investigating the relationships between expression of p53 detected by immunohistochemistry and prognosis of gastric cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival and disease-free survival. Results: A total of 4.330 patients from 21 studies were included in the analysis. Our results showed tissue p53 overexpression in patients with gastric cancer to be associated with poor prognosis in terms of overall survival (HR, 1.610; 95% CI, 1.394 -5.235; p:<0.001). Pooled hazard ratio for disease free survival showed that p53 positivity or negativity were not statitistically significant (HR, 1.219; 95%CI, 0.782-1.899; p:0.382). Conclusions: The present meta-analysis indicated overexpression of p53 detected by immunohistochemistry to be associated with a poor prognosis in patients with gastric cancer.


  1. Aizawa K, Ueki K, Suzuki S, et al (1999). Apoptosis and Bbcl-2 expression in gastric carcinomas: correlation withclinicopathological variables, p53 expression, cell proliferation and prognosis. Int J Oncol, 14, 85-91.
  2. Al-Moundhri MS, Nirmala V, Al-Hadabi I, et al (2005). The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients. J Surg Oncol, 91, 243-52.
  3. Bani-Hani KE, Almasri NM, Khader YS, Sheyab FM, Karam HN (2005). Combined evaluation of expressions of cyclin E and p53 proteins as prognostic factors for patients with gastric cancer. Clin Cancer Res, 11, 1447-53.
  4. Begnami MD, Fregnani JH, Nonogaki S, Soares FA (2010). Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication. Hum Pathol, 41, 1120-7.
  5. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101.
  6. Cunningham D, Allum WH, Stenning SP, et al (2006). MAGIC Trial Participants: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med, 355, 1-20.
  7. Danesi DT, Spano M, Fabiano A, et al (2000). Flow cytometric DNA ploidy, p53, PCNA, and c-erbB-2 protein expressions as predictors of survival in surgically resected gastric cancer patients. Cytometry, 42, 27-34.<27::AID-CYTO5>3.0.CO;2-N
  8. Egger M, Davey Smith G, Schneider M, Minder C (1997). Bias in meta-analysis detected by a simple, graphical test. British Med J, 315, 629-34.
  9. Fondevila C, Metges JP, Fuster J, et al (2004). p53 and VEGF expression are independent predictors of tumor recurrence and survival following curative resection of gastric cancer. Br J Cancer, 90, 206-15.
  10. Glimelius B, Ekstrom K, Hoffman K, et al (1997). Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol, 8, 163-8.
  11. Goncalves AR, Carneiro AJ, Martins I, et al (2011). Prognostic significance of p53 protein expression in early gastric cancer. Pathol Oncol Res, 17, 349-55.
  12. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991). P53 mutations in human cancers. Science, 253, 49-53.
  13. Ide M, Kato T, Ogata K, et al (2012). Keratin 17 expression correlates with tumor progression and poor prognosis in gastric adenocarcinoma. Ann Surg Oncol, 19, 3506-14.
  14. Ikeguchi M, Saito H, Kondo A, et al (1999). Mutated p53 protein expression and proliferative activity in advanced gastric cancer. Hepatogastroenterol, 46, 2648-53.
  15. Joypaul BV, Hopwood D, Newman EL, et al (1994). The prognostic significance of the accumulation of p53 tumorsuppressor gene protein in gastric adenocarcinoma. Br J Cancer, 69, 943-6.
  16. Karim S (2014). Clinicopathological and p53 gene alteration comparison between young and older patients with gastric cancer. Asian Pac J Cancer Prev, 15, 1375-9
  17. Lain S, Hollick JJ, Campbell J, et al (2008). Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell, 13, 454-63.
  18. Lazar D, Taban S, Sporea I, et al (2010). The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients. Rom J Morphol Embryol, 51, 249-57.
  19. Lee HK, Lee HS, Yang HK, et al (2003). Prognostic significance of Bcl-2 and p53 expression in gastric cancer. Int J Colorectal Dis, 18, 518-25.
  20. Lim BH, Soong R, Grieu F, et al (1996). p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma. Int J Cancer, 69, 200-4.<200::AID-IJC9>3.0.CO;2-3
  21. Liu XP, Tsushimi K, Tsushimi M, et al (2001). Expression of p21(WAF1/CIP1) and p53 proteins in gastric carcinoma: its relationships with cell proliferation activity and prognosis. Cancer Lett, 170, 183-9.
  22. Liu X, Wang S, Xia X, et al (2012). Synergistic role between p53 and JWA: prognostic and predictive biomarkers in gastric cancer. PLoS One, 7, 52348.
  23. Liu Y, Xing R, Zhang X, et al (2013). miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells. DNA Repair, 12, 741-50.
  24. Lin X, Howell SB (2006). DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol Cancer Ther, 5, 1239-47.
  25. Maehara Y, Tomoda M, Hasuda S, et al (1999). Prognostic value of p53 protein expression for patients with gastric cancer--a multivariate analysis. Br J Cancer. 79, 1255-61.
  26. Martin HM, Filipe MI, Morris RW, Lane DP, Silvestre F (1992). p53 expression and prognosis in gastric carcinoma. Int J Cancer, 50, 859-62.
  27. Mrena J, Wiksten JP, Kokkola A, et al (2010). COX-2 is associated with proliferation and apoptosis markers and serves as an independent prognostic factor in gastric cancer. Tumour Biol, 31, 1-7.
  28. Murakami D, Tsujitani S, Osaki T, et al (2007). Expression of phosphorylated Akt (pAkt) in gastric carcinoma predicts prognosis and efficacy of chemotherapy. Gastric Cancer, 10, 45-51.
  29. Nguyen S, Rebischung C, Van Ongeval J, et al (2006). Epirubicin-docetaxel in advanced gastric cancer: two phase II studies as second and first line treatment. Bull Cancer, 93, 1-6.
  30. Ochiai A, Yamauchi Y and Hirohashi S (1996). p53 mutations in the non-neoplastic mucosa of the human stomach showing intestinal metaplasia. Int J Cancer, 69, 28-33.<28::AID-IJC6>3.0.CO;2-Y
  31. Sezer C, Yildirim M, Yildiz M, et al (2013). Prognostic significance of biological apoptosis factors in gastric cancer. J Buon, 18, 138-46.
  32. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.
  33. Pietrantonio F, De Braud F, Da Prat V, et al (2013). A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res, 33, 1257-66.
  34. Roy A, Cunningham D, Hawkins R, et al (2012). Docetaxel combined with irinotecan or 5-fluorouracil in patients with advanced oesophago-gastric cancer: a randomised phase II study. Br J Cancer, 107, 435-41.
  35. Sereno M, De Castro J, Cejas P, et al (2012). Expression profile as predictor of relapse after adjuvant treatment in gastric cancer. J Gastrointest Cancer, 43, 181-9.
  36. Sgambato A, Migaldi M, Leocata P, et al (2000). Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in N0 gastric carcinomas. Cancer, 89, 2247-57.<2247::AID-CNCR13>3.0.CO;2-5
  37. Song KY, Jung CK, Park WS, Park CH (2009). Expression of the antiapoptosis gene survivin predicts poor prognosis of stage III gastric adenocarcinoma. Jpn J Clin Oncol, 39, 290-6.
  38. Tanner M, Hollmen M, Junttila TT, et al (2005). Amplification of HER-2 in gastric carcinoma: association with topoisomerase IIa gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol, 16, 273-278.
  39. Torres J, Correa P, Ferreccio C, et al (2013). Gastric cancer incidence and mortality is associated with altitude in the mountainous regions of pacific latin America. Cancer Causes Control, 24, 249-56.
  40. Tsujitani S, Saito H, Wakatsuki T, et al (2012). Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer. Surg Today, 42, 225-32.
  41. Tzanakis NE, Peros G, Karakitsos P, et al (2009). Prognostic significance of p53 and Ki67 proteins expression in Greek gastric cancer patients. Acta Chir Belg, 109, 606-11.
  42. Victorzon M, Nordling S, Haglund C, Lundin J, Roberts PJ (1996). Expression of p53 protein as a prognostic factor in patients with gastric cancer. Eur J Cancer, 32, 215-20.
  43. Ye YW, Zhang X, Zhou Y, et al (2012). The correlations between the expression of FGFR4 protein and clinicopathological parameters as well as prognosis of gastric cancer patients. J Surg Oncol, 106, 872-9.
  44. Zha Y, Cun Y, Zhang Q, Li Y, Tan J (2012). Prognostic value of expression of Kit67, p53, TopoIIa and GSTP1 for curatively resected advanced gastric cancer patients receiving adjuvant paclitaxel plus capecitabine chemotherapy. Hepatogastroenterol, 59, 1327-32.
  45. Zhang Y, Zhang Q, Zeng SX, Hao Q, Lu H (2013). Inauhzin sensitizes p53-dependent cytotoxicity and tumor suppression of chemotherapeutic agents. Neoplasia, 15, 523-34.
  46. Wells GA, Brodsky L, O'Connell D (2003). An evaluation of the newcastle ottawa scale: an assessment tool for evaluating the quality of non-randomized studies. XI Cochrane Colloquium, 63, 26.

Cited by

  1. Expression, correlation, and prognostic value of TRAF2 and TRAF4 expression in malignant plural effusion cells in human breast cancer vol.43, pp.11, 2015,
  2. Poorly Differentiated Medullary Phenotype Predicts Poor Survival in Early Lymph Node-Negative Gastro-Esophageal Adenocarcinomas vol.11, pp.12, 2016,
  3. The Role of p53 Gene in Cervical Carcinogenesis vol.66, pp.S1, 2016,
  4. Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer vol.53, pp.2, 2017,
  5. Prognostic Value and Clinicopathological Significance of p-stat3 Among Gastric Carcinoma Patients vol.95, pp.5, 2016,
  6. Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer vol.9, pp.1, 2018,
  7. Incorporation of p-53 mutation status and Ki-67 proliferating index in classifying Her2-neu positive gastric adenocarcinoma vol.13, pp.1, 2018,