Expression of carbonic anhydrase IX in the breast carcinomas

Česká verzia

Authors: K. Kajo ¹; I. Turčan ²; M. Vallová ¹; T. Laboš ¹; M. Kajo ¹; K. Macháleková ¹; Š. Galbavý ^1,3; P. Žúbor ⁴
Authors place of work: Ústav patológie Slovenskej zdravotníckej univerzity a Onkologického ústavu svätej Alžbety, Bratislava, prednosta doc. MUDr. K. Kajo, PhD. ¹; Mammacentrum svätej Agáty, s. r. o., Banská Bystrica, primár MUDr. I. Turčan ²; Ústav súdneho lekárstva Lekárskej fakulty Univerzity Komenského, Bratislava, prednosta prof. MUDr. Š. Galbavý, DrSc. ³; Gynekologicko-pôrodnícka klinika Jesseniovej lekárskej fakulty Univerzity Komenského a Univerzitnej nemocnice, Martin, prednosta prof. MUDr. J. Danko, CSc. ⁴
Published in the journal: Ceska Gynekol 2013; 78(3): 263-268

Summary

Objective:
Carbonic anhydrase IX (CA IX) is one indicator of hypoxia in the tumor and its expression is associated with more aggressive forms of breast cancer. The aim of this study is to point out its own set of correlation between CA IX expression and selected morphological and biological indicators.

Type of study:
Cohort prospective study.

Setting:
Department of Pathology of Slovak Medical University and St. Elisabeth Cancer Institute, Bratislava, Slovak Republic.

Methods:
These were 145 cases of breast cancer aged 25 to 85 years (median 59 years) from the Register of the Institute of Pathology and Slovak Medical University and St. Elisabeth Cancer Institute in Bratislava for the period 1. 9. 2012 to 28. 2. 2013. In all cases were examined CA IX, estrogen receptor (ER), progesterone receptor (PR), HER2, p53 and Ki67 by immunohistochemistry. Typing, grading and staging of the disease were evaluated according to the classification systems currently in place.

Results:
CA IX expression was demonstrated in 51 cases (35.2%). CA IX positivity correlated with the degree of differentiation (p = 0.0001), with ER status (p <0.0001) and PR (p <0.01) and HER2 (p <0.01) and proliferative activity as measured by Ki67 (p <0.001). HER2-positive cancers and triple-negative cancers were more frequently associated with the expression of CA IX compared with luminal subtypes (p <0.0001). The state of CA IX and age range of the tumor – pT and lymph node status - pN and p53 have not been shown statistically significant correlations.

Conclusion:
CA IX examination in breast cancer provides valuable information on the state of hypoxia in the tumor, thereby supplementing view of prognosis of the disease.

Keywords:
breast – carbonic anhydrase IX – immunohistochemistry – prognosis

Zdroje

1. Bartosova, M., Parkkila, S., Pohlodek, K., et al. Expression of carbonic anhydrase IX v breast is associated with malignant tissues and is related to overexpression of cerbB2. J Pathol, 2002, 197, p. 314–321.

2. Bennewith, KL., Dedhar, S. Targeting hypoxic tumour cells to overcome metastasis. BMC Cancer, 2011, 11, p. 504.

3. Betof, AS., Rabbani, ZN., Hardee, ME., et al. Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification. Br J Cancer, 2012, 106, p. 916–922.

4. Brennan, DJ., Jirstrom, K., Kronblad, A., et al. CA IX is an independent prognostic marker in premenopausal breast cancer patients with one to three positive lymph nodes and a putative marker of radiation resistance. Clin Cancer Res, 2006, 12, p. 6421–6431.

5. Edge, SE., Byrd, DR., Compton, CC., et al. AJCC Cancer Staging Handbook. From the AJCC Cancer Staging Manual,7th ed., Springer 2010, pp. 718, ISBN 978-0-387-88442-4.

6. Elstonm, CW., Ellis, IO. Pathological prognostic factors in breast cancer I. The value of histological grade in breast cancer: experience from a large study with long-term followup, Histopathology, 1991, 19, p. 403–410.

7. Favaro, E., Lord, S., Harris, AL., Buffa, FM. Gene expression and hypoxia in breast cancer. Genome Med, 2011, 3, p. 55.

8. Gieling, RG., Williams, KJ. Carbonic anhydrase IX as a target for metastatic disease. Bioorg Med Chem, 2012, doi: 10.1016/j.bmc.2012.09.062.

9. Goldhirsch, A., Wood, WC., Coates, AS., et al. Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol, 2011, 22, p. 1736–1747.

10. Hammond, ME., Hayes, DF., Dowsett, M., et al. American Society of Clinical Oncology / College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol, 2010, 28, p. 2784–2795.

11. http://www3.mdanderson.org

12. Hussain, SA., Ganesan, R., Reynolds, G., et al. Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer. Br J Cancer, 2007, 96, p. 104–109.

13. Chia, SK., Wykoff, CC., Watson, PH., et al. Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase IX, in invasive breast carcinoma. J Clin Oncol, 2001, 19, p. 3660–3668.

14. Lakhanim, SR., Ellis, IO., Schnitt, SJ., et al. WHO Classification of tumours of the breast. Lyon, IARC, 2012, pp. 240.

15. Lou, Y., McDonald, PC., Oloumi, A., et al. Targeting tumor hypoxia: suppression of breast tumor growth and metastasis by novel carbonic anhdrase IX inhibitors. Cancer Res, 2011, 71, p. 3364–3376.

16. McDonald, PC., Winum, JY., Supuran, CT., Dedhar, S. Recent developments in targeting carbonic anhydrase IX for cancer therapeutics. Oncotarget, 2012, 3, p. 84–97.

17. Muller, V., Riethdorf, S., Rack, B., et al. Prospective evaluation of serum tissue inhibitor of metallloproteinase I and carbonic anhydrase IX in correlation to circulating tumor cells in patients with metastatic breast cancer. Breast Cancer Res 2011, 13, p. R71.

18. Pastorekova, S., Zavada, J. Carbonic anhydrase (CA IX) as a potential target for cancer therapy. Review article. Cancer Ther, 2004, 2, p. 245–262.

19. Saarnio, J., Parkkila, S., Parkkila, AK., et al. Immuno-histochemistry of carbonic anhydrase IX (MN/CAIX) in human gut reveals polarized expression in the epithelial cells with the highest proliferative capacity. J Histochem Cytochem, 1998, 46, p. 497–504.

20. Silverstein, MJ. The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ. Am J Surg, 2003, 186, p. 337–343.

21. Span, PN., Bussink, J., de Mulder, PH., Sweep, FCGJ. Carbonic anhydrase IX expression is more predictive than prognostic in breast cancer. Br J Cancer, 2007, 96, p. 1309.

22. Supuran, CT. Inhibition of carbonic anhydrase IX as a novel anticancer mechanism. World J Clin Oncol, 2012, 3(7), p. 98–103.

23. Takacova, M., Bartosova, M., Skvarkova, L., et al. Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma. Oncol Letters, 2013, 5, p. 191–197.

24. Ward, C., Langdon, SP., Mullen, P., et al. New strategies for targeting the hypoxic tumour microenvironment in breast cancer. Cancer Treat Rev, 2013, 39(2), p. 171–179.

25. Wolff, AC., Hammond, ME., Schwartz, JN., et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol, 2007, 25, p. 118–145.