Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression.

Purpose: The purpose of this study is to address the hypothesis that activatedmitogen-activated protein kinase (MAPK; extracellular signal-regulated kinases 1 and 2) has a role in breast tumorigenesis, breast cancer progression, and the development of tamoxifen resistance.

Experimental Design: H-score analysis and a specific antibody for the immunohistochemical detection of activated MAPK in formalin-fixed, paraffin-embedded tissue sections were used to compare expression in: (a) human breast tumors and their matched adjacent normal breast tissue; (b) primary human breast tumors and their matched lymph node metastases; and (c) primary breast tumors from patients who later proved to be sensitive or resistant to tamoxifen treatment.

Results: Active MAPK expression was detected in 48% of primary human breast tumors and was significantly increased in tumors compared with adjacent normal breast (Wilcoxon test, P = 0.