Differential p53 protein expression in breast cancer fine needle aspirates: the potential for in vivo monitoring

Fine needle aspiration (FNA) biopsy is the least invasive method of samplin g breast cancer in vivo and provides material for breast cancer diagnosis. FNA has also been used to examine cellular markers to predict and monitor t he effects of therapy. The aim of this study was to assess the accuracy of using FNA material compared with resected cancer for Western blotting studi es of the p53 pathway, a key to tumour response to radiotherapy and chemoth erapy. Paired samples of breast cancer FNAs collected pre-operatively and p ost-operatively were compared with tissue samples obtained at the time of s urgical resection. Western blots were probed for p53 using the antibodies D O12 and DO1, and for levels of downstream proteins p21/WAF1 and p27. The pr otein extracted by FNA was sufficient for up to 5 Western blot studies. p53 expression and phosphorylation did not differ significantly pre- and post- operatively, indicating that intra-operative manipulation does not affect p 53 expression or downstream activation in breast cancer. However, expressio n of p53, p21 and p27 varied between individual patients suggesting a range of p53 pathway activation in breast cancer. Immunohistochemistry confirmed that the cancer cells accounted for the protein expression detected on Wes tern blots. FNA yields adequate protein for Western blotting studies and co uld be used as a method to monitor p53 activity in vivo before and during a nti-cancer treatment possibly providing early evidence of tumour response t o therapy. (C) 2001 Cancer Research Campaign.