Osteopontin-C expression predicts DCIS breast cancer progression
MedWire News: Women with ductal carcinoma in situ (DCIS) whose tumors express the marker osteopontin-c are at risk for progression to invasive breast cancer, study results suggest.
The researchers claim that osteopontin-c is a more sensitive diagnostic and prognostic marker in this setting than estrogen receptor (ER), progesterone receptor (PR) and HER-2 expression.
"The problem with these biomarkers is that many of them are present at some level in the normal breast," said lead investigator Georg Weber from the University of Cincinnati, Ohio, USA.
He added: "In addition, they are surface molecules that support growth so they are not necessarily a good predictor of tumor metastasis."
The researchers enrolled 20 women with DCIS, and took samples from the tumor and surrounding tissue. Breast tissue samples were also taken from women without a history of breast cancer.
Total messenger (m)RNA was extracted from tissue samples and osteopontin-c expression was measured by polymerase chain reaction (PCR).
As reported in the International Journal of Cancer, osteopontin-c was abundantly expressed in 16 of 20 tumors, but was undetectable in 22 normal breast samples.
These findings were confirmed by immunohistochemistry, showing osteopontin-c staining in 43 of 56 breast cancers, but only three of 69 normal breast samples.
Weber et al report that the intensity of osteopontin-c staining increased more than 2-fold from grade 1-3 DCIS.
The researchers also measured expression of ER, PR, and HER-2 in the same 56 tumors. In all, 20 tumors were positive for ER expression, 19 were positive for PR expression, and 26 were HER-2 positive.
ER and PR were substantially reduced in higher grade tumors while HER-2 was slightly higher in grades 2 and 3 than in grade 1.
After logistic regression modelling, osteopontin-c was a better predictor of grade 3 DCIS than all other markers.
"If we know that this molecule is not present in a patient with breast cancer, it's more likely that we can treat them with conservative therapy rather than breast surgery, hormone therapy or chemotherapy because we know it's less likely to metastasize," said Weber.
"On the other hand, if we know that a patient has this molecule early in their diagnosis, we can treat it more aggressively because we know their cancer is likely to become invasive," he added.
Int J Cancer 2007; Advance online publication
http://www3.interscience.wiley.com/cgi-bin/jhome/29331
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