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Metabolic classification of human rectal adenocarcinomas: a novel guideline for clinical oncologists?

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Abstract

Purpose

Based on previous findings in SCC of the human uterine cervix and of the head and neck, metastasis- and survival-related metabolic classification was performed in human rectal adenocarcinomas. Such a characterization is suggested as basis of a novel clinical guideline for an appropriate therapy of epithelium-derived malignancies.

Methods

Tissue concentrations of ATP, glucose, and lactate in viable tumor regions of 33 pretherapeutically taken cryobiopsies from 24 patients were measured at a microscopic level using the technique of imaging bioluminescence.

Results

In metastatic carcinomas, lactate levels were significantly higher (mean±SD: 13.4±3.8 vs 6.9±2.5 µmol/g, P = 0.0046) and glucose levels significantly lower (0.3±0.2 vs 1.0±0.4 µmol/g, P = 0.0020) than in non-metastatic carcinomas. No patients had distant metastasis with tumor lactate levels below the population median of 8.0 µmol/g or glucose levels above 0.9 µmol/g.

Conclusions

These results support the hypothesis that lactate and glucose levels measured in human primary carcinomas may serve as an early prognostic tool in the clinic with regard to formation of metastasis and patient survival. The present data encourage further studies on possible strategies for a metabolic classification of tumors as a prognostic tool.

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References

  • Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Bean JM, Prosnitz LR, Dewhirst MW (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943

    CAS  PubMed  Google Scholar 

  • Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW (1997) Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 38:285–289

    CAS  PubMed  Google Scholar 

  • Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller-Klieser W (2001) Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys 51:349–353

    CAS  PubMed  Google Scholar 

  • Firth JD, Ebert BL, Ratcliffe PJ (1995) Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. J Biol Chem 270:21021–21027

    Article  CAS  PubMed  Google Scholar 

  • Fyles AW, Milosevic M, Wong R, Kavanagh MC, Pintilie M, Sun A, Chapman W, Levin W, Manchul L, Keane TJ, Hill RP (1998) Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 48:149–156

    Google Scholar 

  • Gatenby RA, Kessler HB, Rosenblum JS, Coia LR, Moldofsky PJ, Hartz WH, Broder GJ (1988) Oxygen distribution in squamous cell carcinoma metastases and its relationsship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 14:831–838

    CAS  PubMed  Google Scholar 

  • Hoeckel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93:266–276

    CAS  PubMed  Google Scholar 

  • Hoeckel M, Knoop C, Schlenger K, Vorndran B, Baussmann E, Mitze M, Knapstein PG, Vaupel P (1993) Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 26:45–50

    PubMed  Google Scholar 

  • Hoeckel M, Schlenger K, Aral B, Mitze M, Schaeffer U, Vaupel P (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515

    CAS  PubMed  Google Scholar 

  • Hoeckel M, Schlenger K, Hoeckel S, Aral B, Schaeffer U, Vaupel P (1998) Tumor hypoxia in pelvic recurrences of cervical cancer. Int J Cancer 79:365–369

    Article  PubMed  Google Scholar 

  • Kimura H, Braun RD, Ong ET, Hsu R, Secomb TW, Papahadjopoulos D, Hong K, Dewhirst MW (1996) Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res 56:5522–5528

    CAS  PubMed  Google Scholar 

  • Mueller-Klieser W, Walenta S (1993) Geographical mapping of metabolites in biological tissue with quantitative bioluminescence and single photon imaging (Invited review). Histochem J 25:407–420

    CAS  PubMed  Google Scholar 

  • Nordsmark M, Overgaard J (2000) A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. Radiother Oncol 57:39–43

    Article  CAS  PubMed  Google Scholar 

  • Nordsmark M, Alsner J, Keller J, Nielsen OS, Jensen OM, Horsman MR, Overgaard J (2001) Hypoxia in human soft tissue sarcomas: adverse impact on survival and no association with p53 mutations. Br J Cancer 84:1070–1075

    Article  CAS  PubMed  Google Scholar 

  • Rofstad EK (2000) Microenvironment-induced cancer metastasis. Int J Radiat Biol 76:589–605

    Google Scholar 

  • Schwickert G, Walenta S, Sundfor K, Rofstad EK, Mueller-Klieser W (1995) Correlation of high lactate levels in human cervical cancer with incidence of metastasis. Cancer Res 55:4757–4759

    CAS  PubMed  Google Scholar 

  • Sundfor K, Lyng H, Rofstad EK (1998) Tumor hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer 78:822–827

    CAS  PubMed  Google Scholar 

  • Walenta S, Salameh A, Lyng H, Evensen JF, Mitze M, Rofstad E, Mueller-Klieser W (1997) Correlation of high lactate levels in head and neck tumors with incidence of metastasis. Am J Pathol 150:409–415

    CAS  PubMed  Google Scholar 

  • Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, Mueller-Klieser W (2000) High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 60:916–992

    CAS  PubMed  Google Scholar 

  • Walenta S, Schroeder T, Mueller-Klieser W (2002) Metabolic mapping with bioluminescence: basic and clinical relevance. Biomolecular Engineering 18:249–262

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The assistance of Frank van Rey and Marit Hoffmann is gratefully acknowledged. The authors wish to thank Dr. Oliver Thews for his statistical advice. This work was supported by the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (grant 01ZO8801), and by the Deutsche Krebshilfe (grant 70–2710-Mül).

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Correspondence to Wolfgang Mueller-Klieser.

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Walenta, S., Chau, TV., Schroeder, T. et al. Metabolic classification of human rectal adenocarcinomas: a novel guideline for clinical oncologists?. J Cancer Res Clin Oncol 129, 321–326 (2003). https://doi.org/10.1007/s00432-003-0450-x

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  • DOI: https://doi.org/10.1007/s00432-003-0450-x

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