Alteration of Met protooncogene product expression and prognosis in breastcarcinomas

OBJECTIVE: To objectively quantify the expression and prognostic implicatio ns of the met protooncogene product (Met) in human breast cancer. STUDY DESIGN: One hundred eighty-two cases of primary human breast cancer w ere collected. Both the normal and tumor portions of the original surgical pathology specimen were immunostained for Met and imaged using laser scanni ng confocal microscopy. Then the cases were ranked according to relative co ncentrations of normal and tumor Met expression. Subsequently, they were qu antified using image analysis and the results correlated with clinical outc ome to determine the prognostic value of relative levels of Met. RESULTS: Using a quantitative index to evaluate the relative levels of Met expression, high levels of Met expression in the tumor as compared with the adjacent normal ducts predicted poor prognosis for overall survival and me tastasis-ree survival. The risk ratio for elevated Met rxprrssion teas 3.94 (P = .0009). This new method also allows determination of the clinical rel evance of low levels of Met in the tumor. The overall survival between the patient population with higher, lower and unchanged levels of Met in normal tissue as compared to tumor were significantly different (P =.0020). CONCLUSION: Our studies suggest that in a subpopulation of node-negative br east cancer patients, either high or low levels of Met in tremor tissue rel ative to normal tissue is an indicator of poor overall survival (P=.0068). Thus, Met expression could be useful for identifying node-negative patients who could benefit from adjuvant therapy.