Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Prognostic significance of p53 expression in patients with esophageal cancer: a meta-analysis

Authors: Lianghai Wang, Xiaodan Yu, Jing Li, Zhiyu Zhang, Jun Hou, Feng Li

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer.

Methods

Publications that assessed the clinical or prognostic significance of p53 expression in esophageal cancer and were published before July 1, 2015 were identified by searching the PubMed and EMBASE databases. A meta-analysis was performed to clarify the association between p53 expression and the clinical outcomes.

Results

A total of 36 publications met the criteria and included 4577 cases. Analysis of these data showed that p53 expression in esophageal cancer was significantly associated with poorer 5-year survival (RR = 1.30, 95 % CI: 1.11–1.51, P = 0.0008). Subgroup analyses according to histological type, continent of the patients, and cut-off value revealed the similar results. The results also indicated that p53 expression was highly associated with advanced TNM stages (I/II vs. III/IV, OR = 0.74, 95 % CI: 0.55–0.99, P = 0.04), lymph node metastasis (OR = 0.77, 95 % CI: 0.66–0.90, P = 0.001), and distant metastasis (OR = 0.46, 95 % CI: 0.26–0.80, P = 0.006). However, p53 expression in the included studies was not significantly associated with tumor size (≤ 5 cm vs. > 5 cm, OR = 1.13, 95 % CI: 0.92–1.40, P = 0.24), tumor location (upper + middle vs. lower, OR = 0.91, 95 % CI: 0.70–1.17, P = 0.45), grade of differentiation (well + moderate vs. poor, OR = 1.10, 95 % CI: 0.90–1.34, P = 0.35), and the depth of invasion (T1/T2 vs. T3/T4, OR = 0.86, 95 % CI: 0.71–1.03, P = 0.09).

Conclusions

This meta-analysis showed that p53 expression may be a useful biomarker for predicting poorer prognosis in patients with esophageal cancer.
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
2.
Chen J, Wu F, Pei HL, Gu WD, Ning ZH, Shao YJ, Huang J. Analysis of the correlation between P53 and Cox-2 expression and prognosis in esophageal cancer. Oncol Lett. 2015;10(4):2197–203.PubMedPubMedCentral
3.
4.
Jemal A, Simard EP, Dorell C, Noone AM, Markowitz LE, Kohler B, Eheman C, Saraiya M, Bandi P, Saslow D, et al. Annual Report to the Nation on the Status of Cancer, 1975–2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013;105(3):175–201.CrossRefPubMedPubMedCentral
5.
Morita M, Yoshida R, Ikeda K, Egashira A, Oki E, Sadanaga N, Kakeji Y, Yamanaka T, Maehara Y. Advances in esophageal cancer surgery in Japan: an analysis of 1000 consecutive patients treated at a single institute. Surgery. 2008;143(4):499–508.CrossRefPubMed
6.
Peng J, Shao N, Peng H, Chen LQ. Prognostic significance of vascular endothelial growth factor expression in esophageal carcinoma: a meta-analysis. J BUON. 2013;18(2):398–406.PubMed
7.
Wu J, Wu X, Liang W, Chen C, Zheng L, An H. Clinicopathological and prognostic significance of chemokine receptor CXCR4 overexpression in patients with esophageal cancer: a meta-analysis. Tumour Biol. 2014;35(4):3709–15.CrossRefPubMed
8.
9.
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991;51(23 Pt 1):6304–11.PubMed
10.
Wang X, Simpson ER, Brown KA. p53: protection against tumor growth beyond effects on cell cycle and apoptosis. Cancer Res. 2015;75(23):5001–7.CrossRefPubMed
11.
Patel DD, Bhatavdekar JM, Chikhlikar PR, Patel YV, Shah NG, Ghosh N, Suthar TP, Balar DB. Clinical significance of p53, nm23, and bcl-2 in T3-4N1M0 oesophageal carcinoma: an immunohistochemical approach. J Surg Oncol. 1997;65(2):111–6.CrossRefPubMed
12.
Madani K, Zhao R, Lim HJ, Casson AG. Prognostic value of p53 mutations in oesophageal adenocarcinoma: final results of a 15-year prospective study. Eur J Cardiothorac Surg. 2010;37(6):1427–32.CrossRefPubMed
13.
Davelaar AL, Calpe S, Lau L, Timmer MR, Visser M, Ten Kate FJ, Parikh KB, Meijer SL, Bergman JJ, Fockens P, et al. Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett’s esophagus progression prediction: a prospective follow-up study. Genes Chromosomes Cancer. 2015;54(2):82–90.CrossRefPubMed
14.
Pietrantonio F, De Braud F, Da Prat V, Perrone F, Pierotti MA, Gariboldi M, Fanetti G, Biondani P, Pellegrinelli A, Bossi I, et al. A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res. 2013;33(4):1257–66.PubMed
15.
Baas IO, Mulder JW, Offerhaus GJ, Vogelstein B, Hamilton SR. An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol. 1994;172(1):5–12.CrossRefPubMed
16.
Lin J, Albers AE, Qin J, Kaufmann AM. Prognostic significance of overexpressed p16INK4a in patients with cervical cancer: a meta-analysis. PLoS One. 2014;9(9):e106384.CrossRefPubMedPubMedCentral
17.
18.
Dowell SP, Wilson PO, Derias NW, Lane DP, Hall PA. Clinical utility of the immunocytochemical detection of p53 protein in cytological specimens. Cancer Res. 1994;54(11):2914–8.PubMed
19.
Cordon-Cardo C, Dalbagni G, Saez GT, Oliva MR, Zhang ZF, Rosai J, Reuter VE, Pellicer A. p53 mutations in human bladder cancer: genotypic versus phenotypic patterns. Int J Cancer. 1994;56(3):347–53.CrossRefPubMed
20.
21.
Bourdon JC, Khoury MP, Diot A, Baker L, Fernandes K, Aoubala M, Quinlan P, Purdie CA, Jordan LB, Prats AC, et al. p53 mutant breast cancer patients expressing p53gamma have as good a prognosis as wild-type p53 breast cancer patients. Breast Cancer Res. 2011;13(1):R7.CrossRefPubMedPubMedCentral
22.
Zhou X, Zhang G, Tian Y. p53 Status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with Bacillus Calmette-Guerin: a meta-analysis. PLoS One. 2015;10(3):e0119476.CrossRefPubMedPubMedCentral
23.
Wei K, Jiang L, Wei Y, Wang Y, Qian X, Dai Q, Guan Q. The prognostic significance of p53 expression in gastric cancer: a meta-analysis. J Cancer Res Clin Oncol. 2015;141(4):735–48.CrossRefPubMed
24.
Yao D, Cai GH, Chen J, Ling R, Wu SX, Li YP. Prognostic value of p53 alterations in human osteosarcoma: a meta analysis. Int J Clin Exp Pathol. 2014;7(10):6725–33.PubMedPubMedCentral
25.
Liu J, Ma Q, Zhang M, Wang X, Zhang D, Li W, Wang F, Wu E. Alterations of TP53 are associated with a poor outcome for patients with hepatocellular carcinoma: evidence from a systematic review and meta-analysis. Eur J Cancer (Oxford, England : 1990). 2012;48(15):2328–38.CrossRef
26.
Fichter CD, Herz C, Munch C, Opitz OG, Werner M, Lassmann S. Occurrence of multipolar mitoses and association with Aurora-A/-B kinases and p53 mutations in aneuploid esophageal carcinoma cells. BMC Cell Biol. 2011;12:13.CrossRefPubMedPubMedCentral
27.
Yasuda M, Kuwano H, Watanabe M, Toh Y, Ohno S, Sugimachi K. p53 expression in squamous dysplasia associated with carcinoma of the oesophagus: evidence for field carcinogenesis. Br J Cancer. 2000;83(8):1033–8.CrossRefPubMedPubMedCentral
28.
Casson AG, Tammemagi M, Eskandarian S, Redston M, McLaughlin J, Ozcelik H. p53 alterations in oesophageal cancer: association with clinicopathological features, risk factors, and survival. Mol Pathol. 1998;51(2):71–9.CrossRefPubMedPubMedCentral
29.
Rosa AR, Schirmer CC, Gurski RR, Meurer L, Edelweiss MI, Kruel CD. Prognostic value of p53 protein expression and vascular endothelial growth factor expression in resected squamous cell carcinoma of the esophagus. Dis Esophagus. 2003;16(2):112–8.CrossRefPubMed
30.
Bahnassy AA, Zekri ARN, Abdallah S, El-Shehaby AMR, Sherif GM. Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21waf, mdm2, C-erbB2 and impact on survival. Pathol Int. 2005;55(2):53–62.CrossRefPubMed
31.
Egashira A, Morita M, Yoshida R, Saeki H, Oki E, Sadanaga N, Kakeji Y, Tsujitani S, Maehara Y. Loss of p53 in esophageal squamous cell carcinoma and the correlation with survival: analyses of gene mutations, protein expression, and loss of heterozygosity in Japanese patients. J Surg Oncol. 2011;104(2):169–75.CrossRefPubMed
32.
Chanvitan A, Nekarda H, Casson AG. Prognostic value of DNA index, S-phase fraction and p53 protein accumulation after surgical resection of esophageal squamous-cell carcinomas in Thailand. Int J Cancer. 1995;63(3):381–6.CrossRefPubMed
33.
Murata A, Baba Y, Watanabe M, Shigaki H, Miyake K, Karashima R, Imamura Y, Ida S, Ishimoto T, Iwagami S, et al. P53 immunohistochemical expression and patient prognosis in esophageal squamous cell carcinoma. Med Oncol. 2013;30(4):728.CrossRefPubMed
34.
Wang DY, Xiang YY, Tanaka M, Li XR, Li JL, Shen Q, Sugimura H, Kino I. High prevalence of p53 protein overexpression in patients with esophageal cancer in Linxian, China and its relationship to progression and prognosis. Cancer. 1994;74(12):3089–96.CrossRefPubMed
35.
Kato H, Yoshikawa M, Miyazaki T, Nakajima M, Fukai Y, Tajima K, Masuda N, Tsukada K, Fukuda T, Nakajima T, et al. Expression of p53 protein related to smoking and alcoholic beverage drinking habits in patients with esophageal cancers. Cancer Lett. 2001;167(1):65–72.CrossRefPubMed
36.
Flejou JF, Paraf F, Potet F, Muzeau F, Fekete F, Henin D. p53 protein expression in Barrett’s adenocarcinoma: a frequent event with no prognostic significance. Histopathology. 1994;24(5):487–9.CrossRefPubMed
37.
Shimaya K, Shiozaki H, Inoue M, Tahara H, Monden T, Shimano T, Mori T. Significance of p53 expression as a prognostic factor in oesophageal squamous cell carcinoma. Virchows Arch A Pathol Anat Histopathol. 1993;422(4):271–6.CrossRefPubMed
38.
Huang K, Chen L, Zhang J, Wu Z, Lan L, Wang L, Lu B, Liu Y. Elevated p53 expression levels correlate with tumor progression and poor prognosis in patients exhibiting esophageal squamous cell carcinoma. Oncol Lett. 2014;8(4):1441–6.PubMedPubMedCentral
39.
Lam KY, Law S, Tin L, Tung PH, Wong J. The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients. Am J Gastroenterol. 1999;94(8):2060–8.CrossRefPubMed
40.
Chyczewski L, Kozlowski M, Niklinski J, Szyszko J, Laudanski J, Niklinska W. p53 protein expression in resected invasive esophageal cancer. Neoplasma. 1999;46(3):150–5.PubMed
41.
Cavazzola LT, Rosa AR, Schirmer CC, Gurski RR, Telles JP, Mielke F, Meurer L, Edelweiss MI, Kruel CD. Immunohistochemical evaluation for P53 and VEGF (Vascular Endothelial Growth Factor) is not prognostic for long term survival in end stage esophageal adenocarcinoma. Rev Col Bras Cir. 2009;36(1):24–34.CrossRefPubMed
42.
Shang L, Liu HJ, Hao JJ, Jiang YY, Shi F, Zhang Y, Cai Y, Xu X, Jia XM, Zhan QM, et al. A panel of overexpressed proteins for prognosis in esophageal squamous cell carcinoma. PLoS One. 2014;9(10):e111045.CrossRefPubMedPubMedCentral
43.
Kuwahara M, Hirai T, Yoshida K, Yamashita Y, Hihara J, Inoue H, Toge T. p53, p21(Waf1/Cip1) and cyclin D1 protein expression and prognosis in esophageal cancer. Dis Esophagus. 1999;12(2):116–9.CrossRefPubMed
44.
Nita ME, Nagawa H, Tominaga O, Tsuno N, Hatano K, Kitayama J, Tsuruo T, Domene CE, Muto T. p21Waf1/Cip1 expression is a prognostic marker in curatively resected esophageal squamous cell carcinoma, but not p27Kip1, p53, or Rb. Ann Surg Oncol. 1999;6(5):481–8.CrossRefPubMed
45.
Ikeguchi M, Oka S, Gomyo Y, Tsujitani S, Maeta M, Kaibara N. Combined analysis of p53 and retinoblastoma protein expressions in esophageal cancer. Ann Thorac Surg. 2000;70(3):913–7.CrossRefPubMed
46.
Furihata M, Ohtsuki Y, Ogoshi S, Takahashi A, Tamiya T, Ogata T. Prognostic significance of human papillomavirus genomes (type-16, -18) and aberrant expression of p53 protein in human esophageal cancer. Int J Cancer. 1993;54(2):226–30.CrossRefPubMed
47.
Ahn MJ, Jang SJ, Park YW, Choi JH, Oh HS, Lee CB, Paik HK, Park CK. Clinical prognostic values of vascular endothelial growth factor, microvessel density, and p53 expression in esophageal carcinomas. J Korean Med Sci. 2002;17(2):201–7.CrossRefPubMedPubMedCentral
48.
Hashimoto N, Tachibana M, Dhar DK, Yoshimura H, Nagasue N. Expression of p53 and RB proteins in squamous cell carcinoma of the esophagus: their relationship with clinicopathologic characteristics. Ann Surg Oncol. 1999;6(5):489–94.CrossRefPubMed
49.
Makoto O, Takeda A, Ting-Leig L, Shinnichi O, Hisahiro M, Yutaka F, Yoshihiro N, Kobayashi S, Gunji Y, Suzuki T, et al. Prognostic significance of thymidine phosphorylase and p53 co-expression in esophageal squamous cell carcinoma. Oncol Rep. 2002;9(1):23–8.PubMed
50.
Hsu PK, Li AF, Wang YC, Hsieh CC, Huang MH, Hsu WH, Hsu HS. Reduced membranous beta-catenin protein expression is associated with metastasis and poor prognosis in squamous cell carcinoma of the esophagus. J Thorac Cardiovasc Surg. 2008;135(5):1029–35.CrossRefPubMed
51.
Kanamoto A, Kato H, Tachimori Y, Watanabe H, Nakanishi Y, Kondo H, Yamaguchi H, Gotoda T, Muro K, Matsumura Y. No prognostic significance of p53 expression in esophageal squamous cell carcinoma. J Surg Oncol. 1999;72(2):94–8.CrossRefPubMed
52.
Hardwick RH, Barham CP, Ozua P, Newcomb PV, Savage P, Powell R, Rahamin J, Alderson D. Immunohistochemical detection of p53 and c-erbB-2 in oesophageal carcinoma; no correlation with prognosis. Eur J Surg Oncol. 1997;23(1):30–5.CrossRefPubMed
53.
Vijeyasingam R, Darnton SJ, Jenner K, Allen CA, Billingham C, Matthews HR. Expression of p53 protein in oesophageal carcinoma: clinicopathological correlation and prognostic significance. Br J Surg. 1994;81(11):1623–6.CrossRefPubMed
54.
Inada S, Koto T, Futami K, Arima S, Iwashita A. Evaluation of malignancy and the prognosis of esophageal cancer based on an immunohistochemical study (p53, E-cadherin, epidermal growth factor receptor). Surg Today. 1999;29(6):493–503.CrossRefPubMed
55.
Nakamura T, Ide H, Eguchi R, Hayashi K, Hanyu F, Nagasako K, Yukawa M, Asaka K, Fujimori T, Maeda S. Expression of p53 protein related to human papillomavirus and DNA ploidy in superficial esophageal carcinoma. Surg Today. 1995;25(7):591–7.CrossRefPubMed
56.
Cheng TH, Hsu PK, Li AF, Hung IC, Huang MH, Hsu HS. Correlation of p53, MDM2 and p14(ARF) protein expression in human esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2009;135(11):1577–82.CrossRefPubMed
57.
Yao W, Qin X, Qi B, Lu J, Guo L, Liu F, Liu S, Zhao B. Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7(10):7158–63.PubMedPubMedCentral
58.
Takeno S, Noguchi T, Kikuchi R, Uchida Y, Yokoyama S, Muller W. Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma. Cancer. 2002;94(11):2874–81.CrossRefPubMed
59.
Xu XL, Zheng WH, Tao KY, Li XX, Xu WZ, Wang Y, Zhu SM, Mao WM. p53 is an independent prognostic factor in operable esophageal squamous cell carcinoma: a large-scale study with a long follow-up. Med Oncol. 2014;31(11):1–7.CrossRef
60.
Takahashi Y, Noguchi T, Takeno S, Kimura Y, Okubo M, Kawahara K. Reduced expression of p63 has prognostic implications for patients with esophageal squamous cell carcinoma. Oncol Rep. 2006;15(2):323–8.PubMed
61.
Goukon Y, Sasano H, Nishihira T, Nagura H, Mori S. p53 overexpression in human esophageal carcinoma: A correlation with tumor DNA ploidy and two parameter flow cytometric study. Anticancer Res. 1994;14(3 B):1305–12.PubMed
Metadata
Title
Prognostic significance of p53 expression in patients with esophageal cancer: a meta-analysis
Authors
Lianghai Wang
Xiaodan Yu
Jing Li
Zhiyu Zhang
Jun Hou
Feng Li
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2427-6

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Research article

Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast

Technical advance

Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens

Research article

FDG PET/CT as a prognostic biomarker in the era of molecular-targeting therapies: max SUVmax predicts survival of patients with advanced renal cell carcinoma

Research article

Epidemiology of childhood and adolescent cancer in Bangladesh, 2001–2014

Case report

Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma

Case report

Dermatomyositis with anti-TIF-1γ antibodies as a presenting symptom of underlying triple-negative breast cancer: a case report
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits