title: Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.
abstract: Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.
authors.affiliation: Cancer Research UK, Institute For Cancer Studies, University Hospital Birmingham, Edgbaston, Birmingham B15 2TT, UK. s.a.hussain@bham.ac.uk
authors.forename: S A
authors.initials: SA
authors.lastname: Hussain
authors.forename: R
authors.initials: R
authors.lastname: Ganesan
authors.forename: G
authors.initials: G
authors.lastname: Reynolds
authors.forename: L
authors.initials: L
authors.lastname: Gross
authors.forename: A
authors.initials: A
authors.lastname: Stevens
authors.forename: J
authors.initials: J
authors.lastname: Pastorek
authors.forename: P G
authors.initials: PG
authors.lastname: Murray
authors.forename: B
authors.initials: B
authors.lastname: Perunovic
authors.forename: M S
authors.initials: MS
authors.lastname: Anwar
authors.forename: L
authors.initials: L
authors.lastname: Billingham
authors.forename: N D
authors.initials: ND
authors.lastname: James
authors.forename: D
authors.initials: D
authors.lastname: Spooner
authors.forename: C J
authors.initials: CJ
authors.lastname: Poole
authors.forename: D W
authors.initials: DW
authors.lastname: Rea
authors.forename: D H
authors.initials: DH
authors.lastname: Palmer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000737:chemistry; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000737:chemistry; D003627:Data Interpretation, Statistical; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D013194:Staining and Labeling; D015996:Survival Rate; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases