Tumor dormancy: Elevated expression of stanniocalcins in late relapsing breast cancer

BackgroundBreast cancer is known for its propensity to recur even after decades. The biology behind this phenomenon of tumor dormancy is poorly understood. The stanniocalcins (stanniocalcin-1, STC-1 and stanniocalcin-2, STC-2) are 56 kDa homodimeric proteins. They act as pro-survival factors and contribute to the endurance of terminally differentiated cells such as neurons and adipocytes. We investigated whether elevated expression of stanniocalcins also plays a part in the tumor dormancy of breast cancer.MethodsThe expression of STC-1, STC-2 and estrogen receptor (ER) was studied by immunohistochemistry in 72 primary breast cancers and in their metastatic relapses detected before two years, or after 5 or 10 years from primary surgery.ResultsWhen compared to primary tumors with early relapse and their metastases, the expression of STC-1 and STC-2 was significantly higher in relapses occurring after five year (STC-1 p = 0.0012, STC-2 p = 0.004) and even higher in very late relapses occurring 10 years after surgery (STC-1 p = 0.0017, STC-2 p = 0.0001). Moreover, primary tumors with a propensity of very late relapse displayed a higher initial expression of STC-2 (p = 0.0001). A significantly increased frequency of ER expression was found in the very late relapses.ConclusionThese findings suggest that elevated expression of STC-1 or STC-2 act as survival factors also for breast cancer cells and thereby contribute to tumor dormancy.