The influence of intermediate filament changes on metastasis and prognosisin breast cancer

Objective: In cancer cells, loss of the epithelial protein keratin and acqu isition of the mesenchymal vimentin are associated with increased motility and plasticity. We studied the influence of intermediate filament changes o n the metastasis and prognosis of patients with breast cancer. Methods: Paraffin-embedded specimens of 80 invasive ductal breast cancers a nd six human breast cancer cell lines were analyzed immunohistochemically f or the expression of the keratins 8 and 19 and vimentin. The clinical follo w-up was longer than 10 years. Results: High expression of keratin 8 was found in 27.5% of tumors. Patient s with keratin-8-positive tumors had longer disease-free and overall surviv al compared with those with keratin-8-negative tumors (P <0.004). Keratin 1 9 was expressed in 19% of tumors and its presence was not correlated with o utcome. Vimentin was expressed in 21% of tumors and was associated with unf avorable disease-free and overall survival (P <0.003 and 0.006, respectivel y). Cell lines with increasing metastatic potential had a loss of keratin e xpression in favor of an aberrant expression of vimentin. Conclusion: Loss of keratin 8 and aberrant expression of vimentin are assoc iated with early metastasis and a poor prognosis in breast cancer. Changes in the intermediate filament proteins appear to be important steps in the m alignant progression of breast cancer.