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Breast Cancer Protein: A Paradox
– Reported, February 20, 2012
The protein is trefoil factor 3 (TFF3), which is thought to have features for a good prognosis and is higher in well-differentiated low grade tumors.
“Our findings suggest that TFF3 is regulated by estrogen and has beneficial properties in breast epithelia. We propose that early during breast tumorigenesis, TFF3 retains its association with normal functionality of breast epithelial cells. Subsequently, with the loss of tumor cell differentiation, its function is subverted to promote the development of tumors and infiltration and lymph node metastasis,” lead investigator Felicity E.B. May, Ph.D., of the Northern Institute for Cancer Research and the Department of Pathology at Newcastle University, UK, was quoted as saying.
In order to determine the role of the TFF3 protein in breast cancer, researchers had to measure its level in tissue samples from normal breasts, in situ carcinomas, invasive carcinomas, involved lymph nodes, and benign breast lesions. The protein was in the majority of malignant and benign breast lesions. Defined tumor types had higher levels of TFF3 and there turned out to be a positive association between the protein and micro vessel density.
An important finding in the study would be the strength in the relationship between the protein expression and a more metastatic phenotype in invasive breast cancer. The protein had higher levels in primary tumors with associated metastasis as well as a higher expression in malignant cells that have metastasized away from those within the primary tumor.
TFF3 may be one of the genes that mediate the various effects of estrogens in breast cancer. “The paradox remains, however, for both the estrogen receptor and TFF3, that they contribute to the normal physiology of the breast epithelium yet are involved in the progression of cancer. Our study reinforces the view that TFF3 expression merits evaluation as a prognostic biomarker and as a predictive marker of response to therapy. It is probable that its malign effects will be mitigated by adjuvant endocrine therapy in women with hormone-responsive cancers. However, the usefulness of TFF3 as a marker of hormone responsiveness needs to be evaluated,” Dr. Felicity E.B. May, Ph.D., was quoted as saying.
Researchers also evaluated the potential of TFF3 as a biomarker of lymph node metastasis and lymph vascular invasion. The results were that TFF3 has greater predictive power than others, including age, tumor grade, and tumor size and type.
SOURCE: American Journal of Pathology, February 2012