#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Relation between Carbonic Anhydrase IX Serum Level, Hypoxia and Radiation Resistance of Head and Neck Cancers


Authors: V. Rosenberg 1;  S. Pastoreková 2;  M. Zaťovičová 2;  P. Slezák 3;  I. Waczulíková 4;  J. Švec 5
Authors place of work: Oddelenie radiačnej onkológie, FNsP J. A. Reimana Prešov, Slovensko 1;  Virologický ústav SAV, Bratislava, Slovensko 2;  Ústav simulačného a virtuálneho medicínskeho vzdelávania, LF UK v Bratislave, Slovensko 3;  Oddelenie bio­medicínskej fyziky, Fakulta matematiky, fyziky a informatiky UK v Bratislave, Slovensko 4;  Vysoká škola zdravotníctva a sociálnej práce sv. Alžbety, Bratislava, Slovensko 5
Published in the journal: Klin Onkol 2014; 27(4): 269-275
Category: Original Articles

Summary

Background:
Hypoxia of locally advanced head and neck cancers is one of the main causes of their radiation resistance that presents clinically as a persistence of residual tumor disease after radiation therapy. Therefore, detection of tumor hypoxia could be an important predictor of treatment efficacy. Carbonic anhydrase IX (CA IX) is a protein, coded by a homonymous gene, the expression of which increases in tumor tissues at hypoxic conditions. Hence, CA IX represents an endogenic marker of tumor hypoxia, identifiable in tumor tissues, and its soluble extracellular domain can also be detected in body fluids of the patient. The primary endpoint of this study was to explore whether a correlation exists between CA IX serum level and the residual tumor disease after therapy. The secondary endpoint was to find out how the serum concentration of CA IX changes during the course of fractionated radiation therapy.

Materials and Methods:
The presented prospective monocentric clinical study evaluated a population of 30 patients with locally advanced squamous cell head and neck cancers, treated by radiation therapy or concurrent chemo‑ radiation therapy with a curative intent. The serum concentration of the soluble form of CA IX was examined from a venous blood sample, using sandwich enzyme‑linked immunosorbent assay (ELISA). The blood samples were obtained before the treatment initiation, in the middle of radiation therapy, at the time of finishing radiation therapy and six weeks after the treatment completion.

Results:
We found a substantial variability in the CA IX levels measured in the examined population, ranging 0– 1,696 pg/ ml. We found no significant changes in the mean value of CA IX concentration during the course of radiation therapy and after the treatment completion. In 11 patients (36.7%), the treatment resulted in complete remission of the disease. In these patients, lower average pre‑treatment levels of CA IX were noted when compared to patients with persistence of residual tumor disease (37.57 vs 77.47; p = 0.154).

Conclusion:
The results indicate that serum level of CA IX in patients with locally advanced head and neck cancers does not change significantly during the course of fractionated radiation therapy. The relation between CA IX serum level and residual tumor disease after radiation therapy requires verification on a larger population of patients.

Key words:
head and neck cancer –  hypoxia –  carbonic anhydrase IX –  radiation therapy –  residual tumor

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
10. 2. 2014

Accepted:
4. 3. 2014


Zdroje

1. Šlampa P, Petera J. Radiační onkologie. 1. vyd. Praha: Galén 2007: 457.

2. Bencová V. Komunikácia ako súčasť suportívnej terapie v onkológii. Klin Onkol 2013; 26(3): 195– 200.

3. Joiner M, van der Koegel A. Basic clinical radiobio­logy. 4th ed. London: Hodder Arnold 2009: 375.

4. Halperin EC, Perez CA, Brady LW et al. Perez and Brady‘s principles and practice of radiation oncology. 5th ed. Philadelphia: Lippincott Williams & Wilkins 2008: 2106.

5. Brizel DM, Dodge RK, Clough RW et al. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol 1999; 53(2): 113– 117.

6. Gatenby RA, Kessler HB, Rosenblum JS et al. Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 1988; 14(5): 831– 838.

7. Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 1996; 41(1): 31– 39.

8. Nordsmark M, Bentzen SM, Rudat V et al. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi‑center study. Radiother Oncol 2005; 77(1): 18– 24.

9. Isa AY, Ward TH, West CM et al. Hypoxia in head and neck cancer. Br J Radiol 2006; 79(946): 791– 798.

10. Stadler P, Becker A, Feldmann HJ et al. Influence of the hypoxic subvolume on the survival of patients with head and neck cancer. Int J Radiat Oncol Biol Phys 1999; 44(4): 749– 754.

11. Teicher BA. Hypoxia and drug resistance. Cancer Metastasis Rev 1994; 13(2): 139– 168.

12. Raleigh JA, Dewhirst MW, Thrall DE. Measuring tumor hypoxia. Semin Radiat Oncol 1996; 6(1): 37– 45.

13. Gunderson LL, Tepper JE. Clinical radiation oncology. 3rd ed. Philadelphia: Saunders 2012: 1638.

14. Vordermark D, Brown JM. Endogenous markers of tumor hypoxia predictors of clinical radiation resistance? Strahlenther Onkol 2003; 179(12): 801– 811.

15. Hoogsteen IJ, Marres HA, Bussink J et al. Tumor microenvironment in head and neck squamous cell carcinomas: predictive value and clinical relevance of hypoxic markers. A review. Head Neck 2007; 29(6): 591– 604.

16. Parkkila S. Significance of pH regulation and carbonic anhydrases in tumour progression and implications for dia­gnostic and therapeutic approaches. BJU Int 2008; 101 (Suppl 4): 16– 21. doi: 10.1111/ j.1464‑ 410X.2008.07643.x.

17. Pastoreková S, Parkkila S, Závada J. Tumor‑associated carbonic anhydrases and their clinical significance. Adv Clin Chem 2006; 42: 167– 216.

18. Beasley NJ, Wykoff CC, Watson PH et al. Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density. Cancer Res 2001; 61(13): 5262– 5267.

19. Bussink J, Kaanders JH, van der Kogel AJ. Tumor hypoxia at the micro‑regional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers. Radiother Oncol 2003; 67(1): 3– 15.

20. Ivanov S, Liao SY, Ivanova A et al. Expression of hypoxia‑ inducible cell‑ surface transmembrane carbonic anhydrases in human cancer. Am J Pathol 2001; 158(3): 905– 919.

21. Loncaster JA, Harris AL, Davidson SE et al. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen mea-surements and prognosis in locally advanced carcinoma of the cervix. Cancer Res 2001; 61(17): 6394– 6399.

22. Airley RE, Loncaster J, Raleigh JA et al. GLUT‑ 1 and CA IX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding. Int J Cancer 2003; 104(1): 85– 91.

23. Koukourakis MI, Giatromanolaki A, Sivridis E et al. Hypoxia‑ regulated carbonic anhydrase‑ 9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy. Clin Cancer Res 2001; 7(11): 3399– 3403.

24. Závada J, Závadová Z, Zaťovičová M et al. Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients. Br J Cancer 2003; 89(6): 1067– 1071.

25. Zaťovičová M, Sedláková O, Švastová E et al. Ectodomain shedding of the hypoxia‑induced carbonic anhydrase IX is a metalloprotease‑ dependent process regulated by TACE/ ADAM17. Br J Cancer 2005; 93(11): 1267– 1276.

26. Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of malignant tumours. 7th ed. Chichester: Wiley‑ Blackwell 2010: 336.

27. Skillings JH, Mack GA. On the use of a Friedman‑ type statistic in balanced and unbalanced block designs. Technometrics 1981; 23(2): 171– 177.

28. Kock L, Mahner S, Choschzick M et al. Serum carbonic anhydrase IX and its prognostic relevance in vulvar cancer. Int J Gynecol Cancer 2011; 21(1): 141– 148. doi: 10.1097/ IGC.0b013e318204c34f.

29. Woelber L, Kress K, Kersten JF et al. Carbonic anhydrase IX in tumor tissue and sera of patients with primary cervical cancer. BMC Cancer 2011; 11: 12. doi: 10.1186/ 1471‑ 2407‑ 11‑ 12.

30. Woelber L, Mueller V, Eulenburg C et al. Serum carbonic anhydrase IX during first‑line therapy of ovarian cancer. Gynecol Oncol 2010; 117(2): 183– 188. doi: 10.1016/ j.ygyno.2009.11.029.

Štítky
Paediatric clinical oncology Surgery Clinical oncology

Článok vyšiel v časopise

Clinical Oncology

Číslo 4

2014 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#