Molecular biomarkers for advanced renal cell carcinoma: implications for prognosis and therapy.
OBJECTIVE
The aim of this study was to determine reliable predictive biomarkers for patients with metastatic renal cell carcinomas (RCCs) who had received cytokine therapy.


METHODS
Tissue specimens were obtained from 62 patients with metastatic RCCs between 1995 and 2006. Paraffin wax embedded tissues were immunostained for carbonic anhydrase IX (CAIX), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF).


RESULTS
Fifty-two specimens (84%) were assessed as clear cell type, with 5, 3, and 2 tumors showing sarcomatoid, papillary, and undifferentiated features, respectively. With a median 54 months of follow-up, 15/18 responding patients (83%) exhibited high CAIX staining compared with only 24/44 (55%) nonresponding patients (odds ratio, OR, 4.1; 95% confidence interval, CI 1.1-16.5, P = 0.04). There was a positive correlation between maximal COX-2 intensity and response for cytokine therapy (Spearman test P = 0.001; rho = 0.408). Corrected calcium level < or = 10 mg/dl (hazard ratio, HR, 0.1; 95% CI 0.15-0.28; P < 0.001), normal hemoglobin level (HR 0.30; 95% CI 0.15-0.50; P = 0.001), and COX-2 expression > or = 50% (HR 0.33; 95% CI 0.15-0.70; P = 0.008) were significant predictive factors of prolonged overall survival.


CONCLUSIONS
Thus, COX-2 and CAIX seem to be important predictors of outcome in patients with metastatic RCCs and might enhance the prognostic information obtained from pathology specimens.
Kim
Hyo Song
HS
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
Won Seog
WS
Park
Se Hoon
SH
Jung
Chul Won
CW
Choi
Han Yong
HY
Lee
Hyun Moo
HM
Jeon
Seong Soo
SS
Ha
Hongil
H
Hwang
In Gyu
IG
Lee
Seungkoo
S
Lim
Ho Yeong
HY
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases