Carbonic anhydrase IX in early-stage non-small cell lung cancer.
OBJECTIVE
Tumor hypoxia is associated with poor prognosis and increased tumor aggressiveness. Carbonic anhydrase (CA) IX, an endogenous marker for tumor hypoxia, catalyzes the hydration of carbon dioxide into carbonic acid and contributes to the pH regulation of tumor cells. Therefore, CA IX might allow tumors to acclimate to a hypoxic microenvironment, promoting tumor cell proliferation. We hypothesized that CA IX expression is related to tumor cell proliferation and poor disease-free survival in patients with early-stage non-small-cell lung cancer (NSCLC).


METHODS
CA IX expression was measured in 75 resected NSCLC tumors to assess prognostic implications for disease-free survival. The relationship of CA IX expression with microvessel density (MVD) and proliferation (Ki-67) index was assessed via colocalization analysis.


RESULTS
All patients had operable NSCLC (stage I, 58; stage II, 17). CA IX expression was present in 54 (72%) of 75 patients and was associated with tumor necrosis (P < 0.05). CA IX-positive tumor areas showed greater cell proliferation as measured by Ki-67 index (P < 0.05) and less MVD (P < 0.05) than did CA IX-negative areas in colocalization analysis. The percentage of CA IX-positive tumor cells was significantly related to postoperative recurrence and poor disease-free survival (P < 0.05). Ki-67 index and pathologic stage were also independent prognostic factors for worse disease-free survival (P < 0.05).


CONCLUSIONS
CA IX expression of tumor cells may be an indicator for poor disease-free survival in early-stage NSCLC.
Kim
Seok Jin
SJ
Department of Medicine, Thoracic Oncology Program, Duke University Medical Center and Durham Veterans Affairs Hospital, Durham, North Carolina, USA.
Rabbani
Zahid N
ZN
Vollmer
Robin T
RT
Schreiber
Ernst-Gilbert
EG
Oosterwijk
Egbert
E
Dewhirst
Mark W
MW
Vujaskovic
Zeljko
Z
Kelley
Michael J
MJ
D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D018287:Carcinoma, Large Cell / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D049109:Cell Proliferation; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000473:pathology; D009389:Neovascularization, Pathologic; D011184:Postoperative Period; D011379:Prognosis; D015996:Survival Rate
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases