COX-2 is overexpressed in primary prostate cancer with metastatic potential and may predict survival. A comparison study between COX-2, TGF-beta, IL-10 and Ki67.
BACKGROUND
The immune modulating molecules cyclooxygenase-2 (COX-2), transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) have regulatory roles in cancer progression. There are conflicting data regarding the roles of these molecules in prostate cancer. To elucidate the prognostic impact of these proteins and provide information on prognosis and treatment, we compared the expression of COX-2, TGF-beta, and IL-10 in prostate cancer specimens with or without metastases. Ki67 was included as a measure of growth fraction of tumor cells.


METHODS
Digital video analysis images from tumor cell areas and tumor stromal areas were analyzed on formalin fixed, paraffin-embedded and immunohistochemical stained cancer specimens from 59 patients: 32 patients with metastases and 27 patients without clinical, biochemical, or radiological evidence of metastases within 10 years after diagnosis. The expression of COX-2 was scored as negative, weak, moderate, or strong. The expressions of TGF-beta and IL-10 were assessed as proportions of moderately or strongly stained cells. Ki67 was detected as strong nuclear staining in proliferating cells.


RESULTS
In primary cancers in the metastatic group, COX-2, TGF-beta and Ki67 were stronger expressed in epithelial tumor cell and tumor stromal areas compared with non-metastatic cancers (for all markers, p<0.0001). High intensity of COX-2 staining in tumor areas was strongly associated with death from prostate cancer in univariate analyses (hazard ratio [HR] 95% CI, 4.0 (1.1-14.5)). In multivariate analyses, the risk estimate was strengthened but did not reach significance. No associations to death were found for the other markers.


CONCLUSIONS
High expression of COX-2, TGF-beta and Ki67 were in metastatic primary prostate carcinoma compared to non-metastatic cancers. High expression of COX-2 was associated to death from prostate carcinoma.
Richardsen
Elin
E
Department of Pathology, University Hospital of Northern Norway, Tromsø, Norway. elin.richardsen@unn.no
Uglehus
Rebecca Dale
RD
Due
Jan
J
Busch
Christer
C
Busund
Lill-Tove
LT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012004:Rectal Neoplasms / Q000378:metabolism / Q000556:secondary; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000556:secondary
D019394:Ki-67 Antigen; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D051546:Cyclooxygenase 2