Skip to main content

Advertisement

SpringerLink
Log in

The prognostic significance of p53 expression in gastric cancer: a meta-analysis

  • Original Article - Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objective

This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in gastric cancer patients.

Methods

A systematic literature search was conducted to identify eligible studies in PubMed and Embase. The pooled hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95 % confidence intervals (95 % CIs) were used to estimate the effect sizes. Moreover, meta-regression analysis and subgroup analysis were carried out.

Results

A total of 34 studies comprising 6,599 patients were subjected to final analysis. Positive/high p53 expression was significantly associated with poorer overall survival (HR 1.56, 95 % CI 1.23–1.98) and disease-specific survival (HR 1.52, 95 % CI 1.35–1.73). The results also indicated that positive/high p53 expression was significantly associated with gender (OR 1.26, 95 % CI 1.09–1.45), Lauren’s classification (OR 1.68, 95 % CI 1.23–2.29), the depth of invasion (OR 0.68, 95 % CI 0.56–0.83), lymph node metastasis (OR 1.56, 95 % CI 1.23–1.97), TNM stage (OR 0.57, 95 % CI 0.47–0.69), vascular invasion (OR 1.51, 95 % CI 1.18–1.92) and lymphatic invasion (OR 1.38, 95 % CI 1.11–1.72), but not with Bormann type (OR 1.24, 95 % CI 0.91–1.70), grade of differentiation (OR 1.08, 95 % CI 0.82–1.44) or distant metastasis (OR 1.37, 95 % CI 0.92–2.03).

Conclusions

This meta-analysis suggests positive/high p53 expression may be a useful biomarker to predict a poorer prognosis for patients with gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

HR:

Hazard risk

OR:

Odds ratio

CI:

Confidence interval

OS:

Overall survival

DSS:

Disease-specific survival

VEGF:

Vascular endothelial growth factor

COX-2:

Cyclooxygenase-2

IHC:

Immunohistochemistry

References

  • Al-Moundhri MS 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 91:243–252

    Article  CAS  PubMed  Google Scholar 

  • Anderson C, Nijagal A, Kim J (2006) Molecular markers for gastric adenocarcinoma. Mol Diagn Ther 10:345–352

    Article  CAS  PubMed  Google Scholar 

  • Baas IO, Mulder JWR, Offerhaus GJA, Vogelstein B, Hamilton SR (1994) An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol 172:5–12

    Article  CAS  PubMed  Google Scholar 

  • 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 11:1447–1453

    Article  CAS  PubMed  Google Scholar 

  • Bataille F et al (2003) Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancer. Mol pathol 56:286–292

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Begg CB (1988) Publication bias: a problem in interpreting medical data. J R Stat Soc A 151:419–463

    Article  Google Scholar 

  • Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  CAS  PubMed  Google Scholar 

  • Bertuccio P et al (2009) Recent patterns in gastric cancer: a global overview. Int J Cancer 125:666–673

    Article  CAS  PubMed  Google Scholar 

  • Bria E et al (2013) A clinical–biological risk stratification model for resected gastric cancer: prognostic impact of Her2, Fhit, and APC expression status. Ann Oncol 24:693–701

    Article  CAS  PubMed  Google Scholar 

  • Chang F, Syrjänen S, Syrjänen K (1995) Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol 13:1009–1022

    CAS  PubMed  Google Scholar 

  • Chen M, Huang J, Zhu Z, Zhang J, Li K (2013) Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer. BMC Cancer 13:539

    Article  PubMed Central  PubMed  Google Scholar 

  • Cordon-Cardo C et al (1994) p53 mutations in human bladder cancer: genotypic versus phenotypic patterns. Int J Cancer 56:347–353

    Article  CAS  PubMed  Google Scholar 

  • De Angelis R et al (2014) Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE–5-a population-based study. Lancet Oncol 15:23–34

    Article  PubMed  Google Scholar 

  • De Dosso S et al (2013) ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy. Cancer Chemother Pharmacol 72:159–165

    Article  CAS  PubMed  Google Scholar 

  • Diez M et al (2000) P53 protein expression in gastric adenocarcinoma. Negative predictor of survival after postoperative adjuvant chemotherapy. Anticancer Res 20:3929–3933

    CAS  PubMed  Google Scholar 

  • Drebber U et al (2008) The overexpression of c-met as a prognostic indicator for gastric carcinoma compared to p53 and p21 nuclear accumulation. Oncol Rep 19:1477–1483

    PubMed  Google Scholar 

  • Efeyan A, Serrano M (2007) p53: guardian of the genome and policeman of the oncogenes. Cell Cycle (Georgetown, Tex) 6:1006–1010

    Article  CAS  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fenoglio-Preiser CM, Wang J, Stemmermann GN, Noffsinger A (2003) TP53 and gastric carcinoma: a review. Hum Mutat 21:258–270

    Article  CAS  PubMed  Google Scholar 

  • Fondevila C et al (2004) p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 90:206–215

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fu H-L, Shao L, Wang Q, Jia T, Li M, Yang D-P (2013) A systematic review of p53 as a biomarker of survival in patients with osteosarcoma. Tumor Biol 34:3817–3821

    Article  CAS  Google Scholar 

  • Gabbert HE, Muller W, Schneiders A, Meier S, Hommel G (1995) The relationship of p53 expression to the prognosis of 418 patients with gastric carcinoma. Cancer 76:720–726

    Article  CAS  PubMed  Google Scholar 

  • Gurel S et al (1999) Expression of p53 protein and prognosis in gastric carcinoma. J Int Med Res 27:85–89

    CAS  PubMed  Google Scholar 

  • He MM et al (2014) Adjuvant chemotherapy, p53, carcinoembryonic antigen expression and prognosis after D2 gastrectomy for gastric adenocarcinoma. World J Gastroenterol 20:264–273

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    Article  CAS  PubMed  Google Scholar 

  • Huang T-J, Wang J-Y, Lin S-R, Lian S-T, Hsieh J-S (2001) Overexpression of the c-met protooncogene in human gastric carcinoma-correlation to clinical features. Acta Oncol 40:638–643

    Article  CAS  PubMed  Google Scholar 

  • Ide M, Kato T, Ogata K, Mochiki E, Kuwano H, Oyama T (2012) Keratin 17 expression correlates with tumor progression and poor prognosis in gastric adenocarcinoma. Ann Surg Oncol 19:3506–3514

    Article  PubMed  Google Scholar 

  • Inoue M, Tsugane S (2005) Epidemiology of gastric cancer in Japan. Postgrad Med J 81:419–424. doi:10.1136/pgmj.2004.029330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ireland AP, Clark G, DeMeester TR (1997) Barrett’s esophagus. The significance of p53 in clinical practice. Ann Surg 225:17

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  • Joo YE et al (2002) The role of vascular endothelial growth factor (VEGF) and p53 status for angiogenesis in gastric cancer. Korean J Intern Med 17:211–219

    CAS  PubMed  Google Scholar 

  • Joypaul BV et al (1994) The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma. Br J Cancer 69:943–946

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Juvan R, Hudler P, Gazvoda B, Repse S, Bracko M, Komel R (2007) Significance of genetic abnormalities of p53 protein in Slovenian patients with gastric carcinoma. Croat Med J 48:207–217

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kasper HU, Schneider-Stock R, Mellin W, Gunther T, Roessner A (1999) P53-protein accumulation and MDM2-protein overexpression in gastric carcinomas. No apparent correlation with survival. Pathol Res Pract 195:815–820

    Article  CAS  PubMed  Google Scholar 

  • Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304–6311

    CAS  PubMed  Google Scholar 

  • Kelley JR, Duggan JM (2003) Gastric cancer epidemiology and risk factors. J Clin Epidemiol 56:1–9

    Article  PubMed  Google Scholar 

  • Kim HS et al (2011) Advanced detection of recent changing trends in gastric cancer survival: up-to-date comparison by period analysis. Jpn J Clin Oncol 41:1344–1350

    Article  PubMed  Google Scholar 

  • Kountouras J, Zavos C, Chatzopoulos D (2005) Apoptotic and anti-angiogenic strategies in liver and gastrointestinal malignancies. J Surg Oncol 90:249–259

    Article  CAS  PubMed  Google Scholar 

  • Ku JH, Byun S-S, Jeong H, Kwak C, Kim HH, Lee SE (2013) The role of p53 on survival of upper urinary tract urothelial carcinoma: a systematic review and meta-analysis. Clin Genitourin Cancer 11:221–228

    Article  PubMed  Google Scholar 

  • Kubicka S et al (2002) p53 mutation pattern and expression of c-erbB2 and c-met in gastric cancer: relation to histological subtypes, helicobacter pylori infection, and prognosis. Dig Dis Sci 47:114–121

    Article  CAS  PubMed  Google Scholar 

  • Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358:15–16

    Article  CAS  PubMed  Google Scholar 

  • Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49

    CAS  PubMed  Google Scholar 

  • Lazar D 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 51:249–257

    PubMed  Google Scholar 

  • Lee WJ, Shun CT, Hong RL, Wu MS, Chang KJ, Chen KM (1998) Overexpression of p53 predicts shorter survival in diffuse type gastric cancer. Br J Surg 85:1138–1142

    Article  CAS  PubMed  Google Scholar 

  • Lee KE et al (2003) Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. Jpn J Clin Oncol 33:173–179

    Article  PubMed  Google Scholar 

  • Lehrbach DM, Cecconello I, Ribeiro U Jr, Capelozzi VL, Ab’saber AM, Alves VA (2009) Adenocarcinoma of the esophagogastric junction: relationship between clinicopathological data and p53, cyclin D1 and Bcl-2 immunoexpressions. Arq Gastroenterol 46:315–320

    Article  PubMed  Google Scholar 

  • Li M, Brooks CL, Kon N, Gu W (2004) A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell 13:879–886

    Article  CAS  PubMed  Google Scholar 

  • Lim BH, Soong R, Grieu F, Robbins PD, House AK, Iacopetta BJ (1996) p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma. Int J Cancer 69:200–204

    Article  CAS  PubMed  Google Scholar 

  • Liu XP, Tsushimi K, Tsushimi M, Kawauchi S, Oga A, Furuya T, Sasaki K (2001) Expression of p21(WAF1/CIP1) and p53 proteins in gastric carcinoma: its relationships with cell proliferation activity and prognosis. Cancer Lett 170:183–189

    Article  CAS  PubMed  Google Scholar 

  • Liu J et al (2012a) 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 48:2328–2338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu X et al (2012b) Synergistic role between p53 and JWA: prognostic and predictive biomarkers in gastric cancer. PLoS ONE 7:e52348

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maehara Y, Tomoda M, Hasuda S, Kabashima A, Tokunaga E, Kakeji Y, Sugimachi K (1999) Prognostic value of p53 protein expression for patients with gastric cancer: a multivariate analysis. Br J Cancer 79:1255–1261

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Malats N et al (2005) P53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol 6:678–686

    Article  CAS  PubMed  Google Scholar 

  • Matturri L et al (1998) Prognostic significance of different biological markers (DNA index, PCNA index, apoptosis, p53, karyotype) in 126 adenocarcinoma gastric biopsies. Anticancer Res 18:2819–2825

    CAS  PubMed  Google Scholar 

  • Migliavacca M et al (2004) TP53 in gastric cancer: mutations in the l3 loop and LSH motif DNA-binding domains of TP53 predict poor outcome. J Cell Physiol 200:476–485

    Article  CAS  PubMed  Google Scholar 

  • Mrena J, Wiksten JP, Kokkola A, Nordling S, Ristimaki A, Haglund C (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

    Article  CAS  PubMed  Google Scholar 

  • Mrozek A et al (2003) Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability. Cell Death Differ 10:461–467

    Article  CAS  PubMed  Google Scholar 

  • Muller PA, Vousden KH, Norman JC (2011) p53 and its mutants in tumor cell migration and invasion. J Cell Biol 192:209–218

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ott K et al (2003) Chromosomal instability rather than p53 mutation is associated with response to neoadjuvant cisplatin-based chemotherapy in gastric carcinoma. Clin Cancer Res 9:2307–2315

    CAS  PubMed  Google Scholar 

  • Pakos EE, Kyzas PA, Ioannidis JP (2004) Prognostic significance of TP53 tumor suppressor gene expression and mutations in human osteosarcoma a meta-analysis. Clin Cancer Res 10:6208–6214

    Article  CAS  PubMed  Google Scholar 

  • Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834

    Article  CAS  PubMed  Google Scholar 

  • Peng L, Zhan P, Zhou Y, Fang W, Zhao P, Zheng Y, Xu N (2012) Prognostic significance of vascular endothelial growth factor immunohistochemical expression in gastric cancer: a meta-analysis. Mol Biol Rep 39:9473–9484

    Article  CAS  PubMed  Google Scholar 

  • Pinto-de-Sousa J, Silva F, David L, Leitao D, Seixas M, Pimenta A, Cardoso-de-Oliveira M (2004) Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma. Histopathology 44:323–331

    Article  CAS  PubMed  Google Scholar 

  • Potrc S, Gadiijev E, Hajdinjak T, Kavalar R (2007) Clinicopathological and immunohistochemical markers after radical gastrectomy for gastric cancer. Hepatogastroenterology 54:308–314

    PubMed  Google Scholar 

  • Puhringer-Oppermann F, Stahl M, Keller G, Sarbia M (2006) Lack of prognostic impact of p53 gene mutation and p53 phosphorylation at serine 15 in multimodally treated adenocarcinomas of the gastroesophageal junction. J Cancer Res Clin Oncol 132:433–438

    Article  PubMed  Google Scholar 

  • Rivera F, Vega-Villegas ME, López-Brea MF (2007) Chemotherapy of advanced gastric cancer. Cancer Treat Rev 33:315–324

    Article  CAS  PubMed  Google Scholar 

  • Roder DM (2002) The epidemiology of gastric cancer. Gastric Cancer 5:5–11

    Article  PubMed  Google Scholar 

  • Roviello F, Marrelli D, Vindigni C, De Stefano A, Spina D, Pinto E (1999) P53 accumulation is a prognostic factor in intestinal-type gastric carcinoma but not in the diffuse type. Ann Surg Oncol 6:739–745

    Article  CAS  PubMed  Google Scholar 

  • Sawada T et al (2014) New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan society for gastroenterological carcinogenesis G-project committee. Gastric Cancer. doi:10.1007/s10120-014-0338-2

  • Sgambato A et al (2000) Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in N0 gastric carcinomas. Cancer 89:2247–2257

    Article  CAS  PubMed  Google Scholar 

  • Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29

    Article  PubMed  Google Scholar 

  • Solcia E et al (2009) A combined histologic and molecular approach identifies three groups of gastric cancer with different prognosis. Virchows Arch 455:197–211

    Article  CAS  PubMed  Google Scholar 

  • 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 39:290–296

    Article  PubMed  Google Scholar 

  • Song J, Su H, Y-y Zhou, L-l Guo (2013) Cyclooxygenase-2 expression is associated with poor overall survival of patients with gastric cancer: a meta-analysis. Dig Dis Sci 59:436–445

    Article  PubMed  Google Scholar 

  • Soussi T (2000) The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann NY Acad Sci 910:121–137

    Article  CAS  PubMed  Google Scholar 

  • Soussi T (2005) The p53 pathway and human cancer. Br J Surg 92:1331–1332. doi:10.1002/bjs.5177

    Article  CAS  PubMed  Google Scholar 

  • Steels E et al (2001) Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 18:705–719

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  PubMed  Google Scholar 

  • Toledo F, Wahl GM (2006) Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 6:909–923

    Article  CAS  PubMed  Google Scholar 

  • Tsujitani S et al (2012) Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer. Surg Today 42:225–232

    Article  CAS  PubMed  Google Scholar 

  • Wang J et al (2011) p53 status and its prognostic role in extrahepatic bile duct cancer: a meta-analysis of published studies. Dig Dis Sci 56:655–662

    Article  PubMed  Google Scholar 

  • Xiao LJ, Zhao S, Zhao EH, Zheng X, Gou WF, Takano Y, Zheng HC (2013) Clinicopathological and prognostic significance of Ki-67, caspase-3 and p53 expression in gastric carcinomas. Oncol Lett 6:1277–1284

    PubMed Central  PubMed  Google Scholar 

  • Xing X, Tang YB, Yuan G, Wang Y, Wang J, Yang Y, Chen M (2013) The prognostic value of E-cadherin in gastric cancer: a meta-analysis. Int J Cancer 132:2589–2596

    Article  CAS  PubMed  Google Scholar 

  • Yoo C, Noh S, Shin D, Choi S, Min J (2000) Recurrence following curative resection for gastric carcinoma. Br J Surg 87:236–242

    Article  CAS  PubMed  Google Scholar 

  • Zafirellis K, Karameris A, Milingos N, Androulakis G (2005) Molecular markers in gastric cancer: can p53 and bcl-2 protein expressions be used as prognostic factors? Anticancer Res 25:3629–3636

    CAS  PubMed  Google Scholar 

  • 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. Hepatogastroenterology 59:1327–1332

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Fundamental Research Funds for the Central Universities (Number: lzujbky-2013-160).

Conflict of interest

All the authors indicated no potential conflicts of interest.

Author information

Authors and Affiliations

  1. The First Clinical Medical College of Lanzhou University, Lanzhou, China

    Kongkong Wei, Yufeng Wang, Xuankun Qian & Qiang Dai

  2. Department of Oncological Surgery, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Cheng Guan District, Lanzhou, 730000, Gansu, China

    Lei Jiang & Quanlin Guan

  3. Department of Critical Care Medicine, Jiuquan People’s Hospital, Jiuquan, China

    Yaoyao Wei

Authors
  1. Kongkong Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaoyao Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yufeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuankun Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiang Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Quanlin Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Quanlin Guan.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 68 kb)

Supplementary material 2 (DOC 59 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, K., Jiang, L., Wei, Y. et al. The prognostic significance of p53 expression in gastric cancer: a meta-analysis. J Cancer Res Clin Oncol 141, 735–748 (2015). https://doi.org/10.1007/s00432-014-1844-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-014-1844-7

Keywords

Search

Navigation