COX-2 is upregulated in many
breast tumors, and one of the products of COX-2 is
PGE2 that is suggested to upregulate
aromatase through cAMP signaling in
breast cancer. Although
aromatase can increase the
estrogen levels in
tumors,
17beta-hydroxysteroid dehydrogenase (17HSD) activity is finally needed for the
estrone/
estradiol regulation. The aim of this study was to investigate if the
protein expression of
enzymes involved in
estrogen synthesis shows covariation with the expression of COX-2. We also wanted to correlate these results with prognosis. We analyzed the expression of COX-2,
aromatase,
17HSD1 and 17HSD2 with immunohistochemistry using tissue microarrays composed of 356 primary
breast tumors. In the present study COX-2 was correlated to
aromatase (P<0.00001),
17HSD1 (P=0.0073), and 17HSD2 (P<0.00001). Patients with ER positive
tumors expressing low amounts of 17HSD2 had decreased
breast cancer survival (P=0.013). Elevated expression of COX-2 and
aromatase was more frequent among larger
tumors (P=0.017 and P=0.013). COX-2 expression correlates with the levels of the examined
steroid converting
enzymes and may contribute to increased
estrogen levels in the
tumor. In
breast cancer cells, the regulatory function of 17HSD2 could be lost, and in the present study patients with low or non-detectable levels of 17HSD2 had worse prognosis than had
breast cancer patients with higher levels of the
enzyme.