Tumor dormancy: elevated expression of stanniocalcins in late relapsing breast cancer.
BACKGROUND
Breast 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 56kDa 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.


METHODS
The 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.


RESULTS
When 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.


CONCLUSIONS
These 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.
Joensuu
Kristiina
K
Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Central Hospital, P.O. Box 21, Haartmaninkatu 3, FI-00290 Helsinki, Finland.
Heikkilä
Päivi
P
Andersson
Leif C
LC
D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011960:Receptors, Estrogen / Q000096:biosynthesis; D013997:Time Factors
D014408:Biomarkers, Tumor; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011960:Receptors, Estrogen; C114997:STC2 protein, human; C051795:teleocalcin