Association of S100A4 and osteopontin with specific prognostic factors and survival of patients with minimally invasive breast cancer.
OBJECTIVE
S100A4 and the estrogen-inducible osteopontin are alone capable of inducing angiogenesis and metastasis in rodent models for breast cancer. The present study assesses the relationship of S100A4 and osteopontin with vessel density and estrogen receptor alpha (ERalpha) in primary tumors and with survival of patients to ascertain their involvement in metastatic breast cancer.


METHODS
Primary tumors from 312 patients treated for minimally invasive human breast cancer were immunocytochemically stained and then assessed for the significance of their association with each other using Fisher's exact test or with patient survival over 18 years of follow-up using Kaplan-Meier plots and Wilcoxon-Gehan statistics.


RESULTS
Antibodies to S100A4 significantly stained endothelial cells of vessels adjacent to S100A4-staining groups of carcinoma cells, and antibodies to osteopontin significantly stained groups of carcinoma cells staining for ERalpha (P < 0.0001). There was a significant association of tumors staining for S100A4 with those with high vessel density (P = 0.021) and of tumors staining for osteopontin with those staining for ERalpha (P = 0.034). The association of staining for S100A4, osteopontin, or vessel density with patient death was significant (P < 0.0001, P = 0.005, and P = 0.014, respectively). The difference in cumulative proportion surviving between S100A4-positive patients with higher or lower vessel density increased up to about 12 years, but thereafter decreased to virtually zero after 18 years of follow-up. Patients with both S100A4-positive and osteopontin-positive primary tumors showed a statistically significant reduction in survival time over those with either one alone (P < 0.019), although in multivariate regression analysis, only staining for S100A4 was significant (P < 0.001).


CONCLUSIONS
It is suggested that in human breast cancer, S100A4 exerts some of its effects through angiogenesis, and that osteopontin is dependent on ERalpha for its expression.
Cancer and Polio Research Fund Laboratories, School of Biological Sciences, Royal Liverpool University Hospital, UK.
Suzete
S
de Silva Rudland
Lee
L
Martin
Chandeene
C
Roshanlall
John
J
Winstanley
Samuel
S
Leinster
Angela
A
Platt-Higgins
Joe
J
Carroll
Christopher
C
West
Roger
R
Barraclough
Philip
P
Rudland
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology; D053495:Osteopontin; D011379:Prognosis; D012044:Regression Analysis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000032:analysis*; D012795:Sialoglycoproteins / Q000032:analysis*; D016019:Survival Analysis; D015996:Survival Rate
D047628:Estrogen Receptor alpha; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; C077591:S100A4 protein, human