Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer

Graeme Walker, Kenneth MacLeod, Alistair R W Williams, David A Cameron, John F Smyth, Simon P Langdon
Gynecologic Oncology 2007, 106 (3): 461-8

OBJECTIVE: To explore the predictive value of estrogen-regulated gene changes as indicators of sensitivity in ovarian cancer patients treated with the aromatase inhibitor Letrozole.

METHODS: Expression of a range of proteins was assessed by semi-quantitative immunohistochemistry in tissue sections from the tumors of patients treated with Letrozole. Expression was correlated with clinical response to Letrozole. Corresponding mRNA in ovarian cancer cell lines treated with 17beta-estradiol (E2) was measured by quantitative RT-PCR.

RESULTS: In an estrogen receptor (ER)-positive ovarian cancer cell line, quantitative RT-PCR analysis demonstrated that PLAU, VIM, BIGH3, CDH6, FN1, CASP4, KRT4, KRT7, KRT13, TRAM and NGAL were down-regulated and TFF1, TFF3, TRAP1, TFAP4, MYC, CTSD, IL17BR, TOP2A, CCNB1, CCNB2, PDZK1 and UBE2C were up-regulated by E2. The E2 modulation of these genes was reversed by the anti-estrogen tamoxifen and was ERalpha-dependent. For ovarian cancer patients treated with Letrozole, we tested the predictive value of the majority of these genes in paraffin sections from their primary tumors by semi-quantitative immunohistochemistry. Significant differences in expression levels of TFF1, TFF3, BIGH3, TRAP1, VIM, TOP2A, PLAU and UBE2C were observed between tumors from CA125 responsive/stable patients as opposed to tumors from patients whose disease progressed, using serum levels of CA125 as an indicator of response. Aromatase expression in the ovarian cancers also differed between these 2 groups of patients.

CONCLUSION: These results suggest that expression levels of certain proteins in ovarian cancers are estrogen-regulated and could help identify patients who would benefit from endocrine therapy.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"