Overexpression of carbonic anhydrase XII in tissues from resectable non-small cell lung cancers is a biomarker of good prognosis.
The pattern of protein expression in tumors is under the influence of nutrient stress, hypoxia and low pH, which determines the survival of neoplastic cells and the development of tumors. Carbonic anhydrase XII (CAXII) is a transmembrane enzyme that catalyzes the reversible hydration of cell-generated carbon dioxide into protons and bicarbonate. Hypoxic conditions activate its transcription and translation and enhanced expression is often present in several types of tumors. The aim of our study was to assess the prognostic significance of CAXII tumor tissues expression in patients with NSCLC. Five hundred fifty-five tumors were immunostained for CAXII on tissue microarrays (TMA) and the results were correlated with clinicopathological parameters and outcome of patients. CAXII overexpression was present in 105/555 (19%) cases and was associated with tumors of lower grade (p = 0.015) and histological type (p < 0.001), being significantly higher in squamous cell carcinoma. High CAXII expression correlated with better overall and disease-specific survival of patients with resectable NSCLC in univariate (p < 0.001) and multivariate survival analyses (p < 0.001). In conclusion, this is the first study demonstrating that a high CAXII tumor tissue expression evaluated on TMAs is related to a better outcome in a large series of patients with resectable NSCLC.
Ilie
Marius I
MI
Laboratory of Clinical and Experimental Pathology, Louis Pasteur Hospital, Nice, France.
Hofman
Véronique
V
Ortholan
Cécile
C
Ammadi
Reda El
RE
Bonnetaud
Christelle
C
Havet
Katia
K
Venissac
Nicolas
N
Mouroux
Jerôme
J
Mazure
Nathalie M
NM
Pouysségur
Jacques
J
Hofman
Paul
P
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D008175:Lung Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms
D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII