Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity.

BACKGROUND

High-dose methotrexate (MTX) is an important component of current protocols for the treatment of osteosarcoma. Although MTX uptake proceeds primarily through the reduced folate carrier (RFC) protein and efflux occurs via multidrug resistance protein 1 (MRP1), RFC protein expression in osteosarcoma remains unexamined.

METHODS

RFC and MRP1 expression (normalized to beta-actin expression) was examined with Western blot analysis in 11 osteosarcoma specimens obtained at diagnosis and 9 osteosarcoma specimens obtained on recurrence.

RESULTS

The average RFC level in specimens obtained on recurrence was significantly higher than the level in specimens obtained at diagnosis (P = 0.0005). Furthermore, in all three matched pairs of diagnosis and recurrence specimens, RFC levels were higher in recurrence specimens than in the corresponding diagnosis specimens. Potential correlations between RFC and MRP1 expression and histologic response to preoperative chemotherapy were examined. Tumors with poor histologic responses (i.e.,

CONCLUSIONS

The significant correlation between low RFC levels at diagnosis and poor histologic response to preoperative chemotherapy suggests that RFC levels at diagnosis may be a useful predictor of chemosensitivity and warrants large-scale studies. In addition, postchemotherapy progression to recurrence is associated with a significant increase in RFC expression. To our knowledge, the current study is the first to examine RFC protein levels in tumor specimens. Cancer 2003.