FOXA1 and AR in invasive breast cancer: new findings on their co-expression and impact on prognosis in ER-positive patients

Abstract

BackgroundThe role of forkhead-box A1 (FOXA1) and Androgen receptor (AR) in breast cancer (BC) has been extensively studied. However, the prognostic role of their co-expression in Estrogen receptor positive (ER+) BC has not been investigated so far. The aim of the present study was thus to assess the co-expression (protein and mRNA) of FOXA1 and AR in BC patients, in order to evaluate their prognostic impact according to ER status.MethodsImmunohistochemical expression of AR and FOXA1 was evaluated on 479 consecutive BC, with complete clinical-pathological and follow up data. Fresh-frozen tissues from 65 cases were available. The expression of AR and FOXA1 with ER was validated using mRNA analyses. Survival and Cox proportional hazard analyses were used to evaluate the relationship between FOXA1, AR and prognosis.ResultsExpression of ER, AR and FOXA1 was observed in 78, 60 and 85% of cases respectively. Most AR+ cases (97%) were also FOXA1+. The level of FOXA1 mRNA positively correlated with level of both AR mRNA (r = 0.8975; P < 0.001) and ER mRNA (r = 0.7326; P < 0.001). In ER+ BC, FOXA1 was associated with a good prognosis independently of AR expression in the three subgroups analyzed (FOXA1+/AR+; FOXA1+/AR-; FOXA1−/AR-). Multivariate analyses confirmed that FOXA1 may provide more information than AR in Disease-Free Interval (DFI) of ER+ BC patients.ConclusionOur results suggest that in BC the expression of FOXA1 is directly related to the expression of AR. Despite that, FOXA1 is found as superior predicting marker of recurrences compared to AR in ER+ BC patients.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4624-y) contains supplementary material, which is available to authorized users.

Androgen Receptor mRNA levels determine the prognosis in triple-negative breast cancer patients

“…These false negatives resulting from IHC seem justified as tumors with positive protein expression were associated with higher mRNA transcript levels (> 10 fold), and was evidenced from the concordance analysis using various threshold levels of AR mRNA. Similar to our findings, Rangel et al demonstrated that cases with no AR protein expression also had a lower AR mRNA transcript levels [31].…”

“…Such an improved quantification method could help in better stratification of TNBC patients for AR directed therapies [27][28][29]. There are very few studies that have investigated AR mRNA expression in BC patients and none of these studies probed into correlation of mRNA expression with disease prognosis [30,31]. In most published studies, AR positivity has been defined as ≥10% tumor nuclei staining [28,32] by IHC.…”

WGCNA reveals key gene modules regulated by the combined treatment of colon cancer with PHY906 and CPT11

“…NANOG is involved in the self-renewal of embryonic stem cells; a previous study indicated that NANOG gene is abnormally overexpressed during the development of malignant phenotype of tumor cells [34]. FOXA1 plays a regulatory role in the evolution and development of organisms, and the recent studies revealed that FOXA1 is associated with a variety of cancers, such as prostate, breast, and gastric [35][36][37]. After filtering for GS and MM value, we eventually obtained 36 hub genes (Loc100041932, 1300001i01rik, Kdelr2, Lasp1, 1110005a03rik, Llgl2, Copa, Orai1, Bcar1, Actn4, Col4a2, Jmjd5, Arrb1, Cry2, Gtf2b, Tmem64, Zfp319, Myadm, Sparc, Ehmt1, Ctgf, Litaf, Psmc6, Sms, Ckmt1, Oat, Zyx, Col18a1, Cox17, Enpp5, Prickle1, Pck2, Slc44a4, Ppap2b, Fn1, and Tpp1) and their expression were significant in distinguishing PHY906-CPT11 and other treatments for colon cancers.…”

Cholesterol metabolism plays a crucial role in the regulation of autophagy for cell differentiation of granular convoluted tubules in male mouse submandibular glands

“…Thus, Foxa1 is a promising target gene of AR signaling in duct development. Mutations in the FOXA1 gene are also associated with the prognosis of human salivary duct carcinoma (Urano et al, 2018), breast cancer (Rangel et al, 2018;Robinson and Carroll, 2012) and prostate cancer (Robinson and Carroll, 2012).…”