Skip to main content

Advertisement

SpringerLink
Log in

Interrelationships between Tumor Proliferative Activity, Leucocyte and Macrophage Infiltration, Systemic Inflammatory Response, and Survival in Patients Selected for Potentially Curative Resection for Gastroesophageal Cancer

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

A number of accepted criteria, including pathological tumor, node, metastasis system stage, lymph node metastasis, and tumor differentiation, predict survival in patients undergoing surgery for gastroesophageal cancer. We examined the interrelationships between standard clinicopathological factors, systemic and local inflammatory responses, tumor proliferative activity, and survival.

Methods

The interrelationships between the systemic inflammatory response (Glasgow prognostic score, mGPS), standard clinicopathological factors, local inflammatory response (Klintrup criteria, macrophage infiltration), and tumor proliferative activity (Ki-67) were examined by immunohistochemistry in 100 patients (44 esophageal [19 squamous, 25 adenocarcinoma], 19 junctional, and 37 gastric cancers) selected for potentially curative resection.

Results

The minimum follow-up was 59 months. On multivariate survival analysis, lymph node ratio (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11–2.40, P < 0.05), tumor differentiation (HR 2.63, 95% CI 1.45–4.77, P = 0.001), mGPS (HR 3.91, 95% CI 1.96–8.11, P < 0.001), Klintrup score (HR 3.47, 95% CI 1.14–10.55, P < 0.05), and Ki-67 (HR 0.67, 95% CI 0.47–0.96, P < 0.05) were independently associated with cancer-specific survival. A higher lymph node ratio was associated with poor tumor differentiation (P < 0.05), low-grade Klintrup criteria (P < 0.005), and low tumor proliferative activity (P < 0.05).

Conclusion

Tumor proliferation rate and local and systemic inflammatory responses are important predictors of survival, albeit in a heterogeneous cohort of patients including esophageal, junctional, and gastric cancers. These scores may be combined with accepted tumor-based factors to improve prediction of outcome.

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

Similar content being viewed by others

References

  1. Cancer Research UK Information Resource Centre. CancerStats. http://infocancerresearchukorg/cancerstats. 2004.

  2. Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis. Cancer. 2000;88:921–32.

    Article  PubMed  CAS  Google Scholar 

  3. Jamieson GG, Mathew G, Ludemann R, Wayman J, Myers JC, Devitt PG. Postoperative mortality following oesophagectomy and problems in reporting its rate. Br J Surg. 2004;91:943–7.

    Article  PubMed  CAS  Google Scholar 

  4. Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg. 1998;228:449–61.

    Article  PubMed  CAS  Google Scholar 

  5. Roder JD, Busch R, Stein HJ, Fink U, Siewert JR. Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the oesophagus. Br J Surg. 1994;81:410–3.

    Article  PubMed  CAS  Google Scholar 

  6. Shiu MH, Perrotti M, Brennan MF. Adenocarcinoma of the stomach: a multivariate analysis of clinical, pathologic and treatment factors. Hepatogastroenterology. 1989;36:7–12.

    PubMed  CAS  Google Scholar 

  7. Robey-Cafferty SS, el-Naggar AK, Sahin AA, Bruner JM, Ro JY, Cleary KR. Prognostic factors in esophageal squamous carcinoma. A study of histologic features, blood group expression, and DNA ploidy. Am J Clin Pathol. 1991;95:844–9.

    PubMed  CAS  Google Scholar 

  8. Khan OA, Alexiou C, Soomro I, Duffy JP, Morgan WE, Beggs FD. Pathological determinants of survival in node-negative oesophageal cancer. Br J Surg. 2004;91:1586–91.

    Article  PubMed  CAS  Google Scholar 

  9. Rosenwald IB. The role of translation in neoplastic transformation from a pathologist’s point of view. Oncogene. 2004;23:3230–47.

    Article  PubMed  CAS  Google Scholar 

  10. Brown DC, Gatter KC. Ki67 protein: the immaculate deception? Histopathology. 2002;40:2–11.

    Article  PubMed  CAS  Google Scholar 

  11. Solcia E, Klersy C, Mastracci L, et al. A combined histologic and molecular approach identifies three groups of gastric cancer with different prognosis. Virchows Arch. 2009;455:197–211.

    Article  PubMed  CAS  Google Scholar 

  12. Ressiot E, Dahan L, Liprandi A, et al. Predictive factors of the response to chemoradiotherapy in esophageal cancer. Gastroenterol Clin Biol. 2008;32:567–77.

    Article  PubMed  CAS  Google Scholar 

  13. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223–6.

    Article  PubMed  Google Scholar 

  14. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30:1073–81.

    Article  PubMed  CAS  Google Scholar 

  15. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.

    Article  PubMed  CAS  Google Scholar 

  16. Ma XC, Hattori T, Kushima R, Terata N, Kodama M. Expression of HLA-class II antigen in gastric carcinomas. Its relationship to histopathological grade, lymphocyte infiltration and five-year survival rate. Acta Oncol. 1994;33:187–90.

    Article  PubMed  CAS  Google Scholar 

  17. Lee HE, Chae SW, Lee YJ, et al. Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer. Br J Cancer. 2008;99:1704–11.

    Article  PubMed  CAS  Google Scholar 

  18. Hyakudomi M, Matsubara T, Hyakudomi R, et al. Increased expression of fractalkine is correlated with a better prognosis and an increased number of both CD8+ T cells and natural killer cells in gastric adenocarcinoma. Ann Surg Oncol. 2008;15:1775–82.

    Article  PubMed  Google Scholar 

  19. Ohno S, Inagawa H, Dhar DK, et al. The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients. Anticancer Res. 2003;23:5015–22.

    PubMed  Google Scholar 

  20. Cho Y, Miyamoto M, Kato K, et al. CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res. 2003;63:1555–9.

    PubMed  CAS  Google Scholar 

  21. Schumacher K, Haensch W, Roefzaad C, Schlag PM. Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res. 2001;61:3932–6.

    PubMed  CAS  Google Scholar 

  22. Klintrup K, Mäkinen JM, Kauppila S, et al. Inflammation and prognosis in colorectal cancer. Eur J Cancer. 2005;41:2645–54.

    Article  PubMed  Google Scholar 

  23. Roxburgh CS, Salmond JM, Horgan PG, Oien KA, McMillan DC. Tumour inflammatory infiltrate predicts survival following curative resection for node-negative colorectal cancer. Eur J Cancer. 2009;45:2138–45.

    Article  PubMed  Google Scholar 

  24. Roxburgh CS, Salmond JM, Horgan PG, Oien KA, McMillan DC. Comparison of the prognostic value of inflammation-based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Ann Surg. 2009;249:788–93.

    Article  PubMed  Google Scholar 

  25. Nozoe T, Saeki H, Sugimachi K. Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma. Am J Surg. 2001;182:197–201.

    Article  PubMed  CAS  Google Scholar 

  26. Shimada H, Nabeya Y, Okazumi S, et al. Elevation of preoperative serum C-reactive protein level is related to poor prognosis in esophageal squamous cell carcinoma. J Surg Oncol. 2003;83:248–52.

    Article  PubMed  Google Scholar 

  27. Ikeda M, Natsugoe S, Ueno S, Baba M, Aikou T. Significant host- and tumor-related factors for predicting prognosis in patients with esophageal carcinoma. Ann Surg. 2003;238:197–202.

    PubMed  Google Scholar 

  28. Gockel I, Dirksen K, Messow CM, Junginger T. Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus. World J Gastroenterol. 2006;12:3746–50.

    PubMed  CAS  Google Scholar 

  29. Crumley AB, McMillan DC, McKernan M, Going JJ, Shearer CJ, Stuart RC. An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. Br J Cancer. 2006;94:1568–71.

    PubMed  CAS  Google Scholar 

  30. Kobayashi T, Teruya M, Kishiki T, et al. Inflammation-based prognostic score, prior to neoadjuvant chemoradiotherapy, predicts postoperative outcome in patients with esophageal squamous cell carcinoma. Surgery. 2008;144:729–35.

    Article  PubMed  Google Scholar 

  31. Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998;85:1457–9.

    Article  PubMed  CAS  Google Scholar 

  32. Going JJ. Efficiently estimated histologic cell counts. Hum Pathol. 1994;25:333–6.

    Article  PubMed  CAS  Google Scholar 

  33. McMillan DC. An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer. Proc Nutr Soc. 2008;67:257–62.

    Article  PubMed  Google Scholar 

  34. Lee HE, Kim MA, Lee BL, Kim WH. Low Ki-67 proliferation index is an indicator of poor prognosis in gastric cancer. J Surg Oncol. 2010;102:201–6.

    Article  PubMed  Google Scholar 

  35. Morley JE, Thomas DR, Wilson MM. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr. 2006;83:735–43.

    PubMed  CAS  Google Scholar 

  36. Fearon KC, Voss AC, Hustead DS. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Am J Clin Nutr. 2006;83:1345–50.

    PubMed  CAS  Google Scholar 

  37. Du Clos TW, Mold C. C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res. 2004;30:261–77.

    Article  PubMed  CAS  Google Scholar 

  38. Krzystek-Korpacka M, Matusiewicz M, Diakowska D, et al. Acute-phase response proteins are related to cachexia and accelerated angiogenesis in gastroesophageal cancers. Clin Chem Lab Med. 2008;46:359–64.

    Article  PubMed  CAS  Google Scholar 

  39. Vashist YK, Loos J, Dedow J, et al. Glasgow prognostic score is a predictor of perioperative and long-term outcome in patients with only surgically treated esophageal cancer. Ann Surg Oncol. In press.

  40. Shearer CJ, Going JJ, Neilson LJ, Stuart RC. Modified classification for adenocarcinoma of the gastro-oesophageal junction. ANZ J Surg. 2007;77:544–9.

    Article  PubMed  Google Scholar 

  41. McColl KE, Going JJ. Aetiology and classification of adenocarcinoma of the gastro-oesophageal junction/cardia. Gut. 2010;59:282–4.

    Article  PubMed  Google Scholar 

  42. Proctor MJ, Morrison DS, Talwar D, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study. Br J Cancer. 2011;104:726–34.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Department of Surgery, Faculty of Medicine, Royal Infirmary, University of Glasgow, Glasgow, Scotland, UK

    Andrew B. C. Crumley MBChB, Mustafa Hilmy MD, Sumanta Dutta MBChB, Claire Tannahill BSc, Margaret McKernan MSc, Joanne Edwards PhD, Robert C. Stuart MD & Donald C. McMillan PhD

  2. University Department of Pathology, Faculty of Medicine, Royal Infirmary, University of Glasgow, Glasgow, Scotland, UK

    James J. Going PhD

Authors
  1. Andrew B. C. Crumley MBChB
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James J. Going PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mustafa Hilmy MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sumanta Dutta MBChB
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claire Tannahill BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Margaret McKernan MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joanne Edwards PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robert C. Stuart MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Donald C. McMillan PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew B. C. Crumley MBChB.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crumley, A.B.C., Going, J.J., Hilmy, M. et al. Interrelationships between Tumor Proliferative Activity, Leucocyte and Macrophage Infiltration, Systemic Inflammatory Response, and Survival in Patients Selected for Potentially Curative Resection for Gastroesophageal Cancer. Ann Surg Oncol 18, 2604–2612 (2011). https://doi.org/10.1245/s10434-011-1658-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-011-1658-7

Keywords

Search

Navigation