Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy.
Clin Cancer Res
; 9(2): 802-11, 2003 Feb.
Article
in En
| MEDLINE
| ID: mdl-12576453
ABSTRACT
PURPOSE:
Metastatic renal cell carcinoma (RCC) has a poor prognosis and an unpredictable course. To date, there are no molecular markers which can reliably predict RCC outcome. We investigated whether a novel kidney cancer marker, carbonic anhydrase IX (CAIX), is associated with progression and survival. EXPERIMENTALDESIGN:
Immunohistochemical analysis using a CAIX monoclonal antibody was performed on tissue microarrays constructed from paraffin-embedded specimens from patients (N = 321) treated by nephrectomy for clear cell RCC. CAIX staining was correlated with response to treatment, clinical factors, pathologic features, and survival.RESULTS:
CAIX staining was present in 94% of clear cell RCCs. Survival tree analysis determined that a cutoff of 85% CAIX staining provided the most accurate prediction of survival. Low CAIX (=85%) staining was an independent poor prognostic factor for survival for patients with metastatic RCC, with a hazard ratio of 3.10 (P < 0.001). CAIX significantly substratified patients with metastatic disease when analyzed by T stage, Fuhrman grade, nodal involvement, and performance status (P < 0.001, = 0.001, = 0.009, = 0.005, respectively). For patients with nonmetastatic RCC and at high risk for progression, low CAIX predicted a worse outcome similar to patients with metastatic disease (P = 0.058). Overall expression of CAIX decreased with development of metastasis; as demonstrated by the lower CAIX staining levels in metastatic lesions relative to matched primary tumor specimens (P = 0.036).CONCLUSIONS:
On the basis of our data, CAIX is the most significant molecular marker described in kidney cancer to date. Decreased CAIX levels are independently associated with poor survival in advanced RCC. CAIX reflects significant changes in tumor biology, which should be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CAIX-targeted therapies.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Renal Cell
/
Carbonic Anhydrases
/
Adenocarcinoma, Clear Cell
/
Kidney Neoplasms
/
Antigens, Neoplasm
/
Neoplasm Proteins
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2003
Document type:
Article
Affiliation country:
United States