Expression of FOXA1 in breast cancer and the significance

Objective: The aim of this study to examine the expression of FOXA1, ER, and PR in breast cancer and investigate the association between FOXA1 expression and clinical parameters. Materials and Methods: One hundred one cases with primary breast cancer were collected and immunohistochemistry was employed to examine the expression of FOXA1, ER, and PR. The correlation of FOXA1 and ER, PR expression with menopausal status, tumor size, clinical stage, histological grade, recurrence, and clinical index relationship was further analyzed. Results: The positive expression of FOXA1 was 67.3%. The positive expression rate of ER in positive FOXA1 group was 66.2% (45/68). The positive expression rate of PR in positive FOXA group was 57.4% (39/68). There was no correlation between FOXA1 expression and menopausal status. Analysis of the relationship between FOXA1 and tumor diameter showed that the percentage of tumor diameter ≤ 2 cm, 2-5 cm, and > 5 cm was 52.9%, 32.4%, and 14.7% in positive FOXA1 group. The correlation with clinical staging showed that the percentage of Stages I, II, and III was 33.8%, 41.2% and 25%, respectively, in positive FOXA1 group. Analysis of histological grade showed that the percentage of grades 1, 2, and 3 was 48.5%, 20.6%, and 23.5%, respectively, in positive FOXA1 group. The positive expression rate of P53 was 30.9%, the recurrence rate was 14.7%, and the positive expression of FOXA1 had better DFS.

Breast cancer; FOXA1; ER; PR; Immunohistochemistry

[1] Siegel R.L., Miller K.D., Jemal A.: “Cancer statistics, 2015”. CA Cancer J. Clin., 2015, 65, 5.

[2] Shou J., Lai Y., Xu J., Huang J.: “Prognostic value of FOXA1 in breast cancer: A systematic review and meta-analysis”. Breast, 2016, 27, 35.

[3] MacNeill F., Karakatsanis A.: “Over surgery in breast cancer”. Breast, 2016, 31, 284.

[4] Rakha E.A., Reis-Filho J.S., Ellis I.O.: “Combinatorial biomarker expression in breast cancer”. Breast Cancer Res. Treat., 2010, 120, 293.

[5] Clark G.M.: “Prognostic and Predictive Factors for Breast Cancer”. Breast Cancer, 1995, 2, 79.

[6] He K., Zeng H., Xu X., Li A., Cai Q., Long X.: “Clinicopathological significance of forkhead box protein A1 in breast cancer: A meta-analysis”. Exp. Ther. Med., 2016, 11, 2525.

[7] Selli C., Dixon J.M., Sims A.H.: “Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers”. Breast Cancer Res., 2016, 18, 118.

[8] Costa R.H., Grayson D.R., Darnell J.E. Jr.: Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes”. Mol. Cell. Biol., 1989, 9, 1415.

[9] Bernardo G.M., Keri R.A.: “FOXA1: a transcription factor with parallel functions in development and cancer”. Biosci. Rep., 2012, 32, 113.

[10] Mehta R.J., Jain R.K., Leung S., Choo J., Nielsen T., Huntsman D., et al.: “FOXA1 is an independent prognostic marker for ER-positive breast cancer”. Breast Cancer Res. Treat., 2012, 131, 881.

[11] Badve S., Turbin D., Thorat M.A., Morimiya A., Nielsen T.O., Perou C.M., et al.: “FOXA1 expression in breast cancer—correlation with luminal subtype A and survival”. Clin. Cancer Res., 2007, 13, 4415.

[12] Golson M.L., Kaestner K.H.: “Fox transcription factors: from development to disease”. Development, 2016, 143, 4558.

[13] Myatt S.S., Lam E.W.: “The emerging roles of forkhead box (Fox) proteins in cancer”. Nat. Rev. Cancer, 2007, 7, 847.

[14] Lupien M., Eeckhoute J., Meyer C.A., Wang Q., Zhang Y., Li W., et al.: “FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription”. Cell, 2008, 132, 958.

[15] Dufour C.R., Wilson B.J., Huss J.M., Kelly D.P., Alaynick W.A., Downes M., et al.: “Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma”. Cell. Metab., 2007, 5, 345.

[16] Cirillo L.A., Lin F.R., Cuesta I., Friedman D., Jarnik M., Zaret K.S.: “Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4”. Mol. Cell., 2002, 9, 279.

[17] Carroll J.S., Liu X.S., Brodsky A.S., Li W., Meyer C.A., Szary A.J.: “Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1”. Cell, 2005, 122, 33.

[18] Cui X., Schiff R., Arpino G., Osborne C.K., Lee A.V.: “Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy”. J. Clin. Oncol., 2005, 23, 7721.

[19] Narod S.A., Feunteun J., Lynch H.T., Watson P., Conway T., Lynch J.: “Familial breast-ovarian cancer locus on chromosome 17q12- q23”. Lancet, 1991, 338, 82.

[20] Gnant M., Harbeck N., Thomssen C.: “St. Gallen 2011: Summary of the Consensus Discussion”. Breast Care (Basel), 2011, 6, 136.

[21] Karnik P.S., Kulkarni S., Liu X.P., Budd G.T., Bukowski R.M.: “Es- trogen receptor mutations in tamoxifen-resistant breast cancer”. Cancer Res., 1994, 54, 349.

[22] Ross-Innes C.S., Stark R., Teschendorff A.E., Holmes K.A., Ali H.R., Dunning M.J.: “Differential oestrogen receptor binding is associated with clinical outcome in breast cancer”. Nature, 2012, 481, 389.

[23] Mottolese M., Nadasi E.A., Botti C., Cianciulli A.M., Merola R., Buglioni S.: “Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer”. J. Cell. Physiol., 2005, 204, 106.

[24] Fisher B., Redmond C., Fisher E.R., Caplan R.: “Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06”. J. Clin. Oncol., 1988, 6, 1076.