Prognostic evaluation of COX-2 expression in renal cell carcinoma.
BACKGROUND
Prognosis of renal cell carcinoma (RCC) differs within the same stage and grade. Our aim was to investigate the incidence of COX-2 in primary RCC tumors at different stages according to the occurrence of metastasis, and the impact of this biomarker on the survival of RCC patients.


METHODS
The cytoplasmic/membranous COX-2 protein expression was examined by immunohistochemistry in RCC tumors from 102 patients. The patients were divided into those with: no metastasis during 7.5 years' follow-up (nm), no metastasis at the time of nephrectomy but who later developed metastases (lm), and those with metastasis at presentation (pm). The immunoreactivity of COX-2 was classified as none (absent/weak intensity in fewer than 10% of the cancer cells), low (weak intensity in over 10% of the cancer cells) or high immunostaining (strong intensity in the majority of the cancer cells). In addition p53 and Ki-67 immunostaining was also assessed in tumors.


RESULTS
Percentages of COX-2 reaction were (no/low/high): 78/16/7 in the nm, 53/28/19 in the lm, 92/8/0 in the pm groups (p=0.014). Median metastasis-free survival was shorter in lm patients with COX-2-negative tumors when compared to those with COX-2-positive ones (15 vs. 46 months; p=0.020). Median overall survival was shorter in pm/lm patients with COX-2-negative tumors when compared to those with COX-2-positive ones (28 vs. 94 months; p=0.027), and with COX-2-negative/Ki-67-positive tumors when compared to COX-2-positive/Ki-67-negative ones (19 vs. 97 months; p=0.004). Findings for patients with COX-2-negative/p53-positive tumors were similar, with shorter survival compared to those with COX-2-positive/p53-negative ones (19 vs. 97; p=0.006).


CONCLUSIONS
COX-2 protein expression is associated with slow development of metastases, and favourable prognosis in metastatic RCC.
Kankuri-Tammilehto
Minna K
MK
Department of Oncology and Radiotherapy, Turku University Hospital, PL 52, FIN-20521 Turku, Finland. minna.kankuri@utu.fi
Söderström
Karl-Ove
KO
Pelliniemi
Tarja-Terttu
TT
Vahlberg
Tero
T
Pyrhönen
Seppo O
SO
Salminen
Eeva K
EK
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000473:pathology; D002462:Cell Membrane / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D003593:Cytoplasm / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2