Prognostic significance of transcription factors FOXA1 and GATA-3 in ductal carcinoma in situ in terms of recurrence and estrogen receptor status

Chivukula, Mamatha; Picarsic, Jennifer; Bulusu, Gautam; Brufsky, Adam; Ahrendt, Gretchen; Carter, Gloria

doi:10.4103/2394-4722.157600

Cited by 4 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FOXA1 has recently been highlighted as a potentially useful marker for triple negative breast cancer 13 , and its expression has been suggested to act as a repressor for a subset of basal signature genes 14 . However, a role for FOXA1 as a subtype marker for DCIS has previously been dismissed as no correlation could be seen with protein expression and that of ER 15 , 16 . Here we also observed that FOXA1 expression does not systematically differ between ER+ and ER- samples, and its reduced expression is only associated with the basal-like TN samples.…”

Section: Resultsmentioning

confidence: 99%

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma

et al. 2022

View full text Add to dashboard Cite

Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…It also promoting E-cadherin expression, thus blocking the migratory capacity and metastasis in breast cancer 6 . Therefore, it is not surprising that FOXA1is highly expressed in ductal carcinoma in situ as well, which by definition is non-invasive carcinoma 20 .…”

Section: Discussionmentioning

confidence: 99%

“…Over the past decade, the biologic role of FOXA1 has been investigated in various human cancers including the mammary 6 , 12 , 13 , prostatic 8 , 10 , hepatocellular 14 , cervical 15 , nasopharyngeal 16 , 17 and colorectal 18 carcinomas, cholangiocarcinoma 19 and ductal carcinoma in situ of the breast 20 using different methodologies, although contradictory data were obtained concerning its prognostic implications and as whether it acts as an oncogene or a tumor-suppressor gene 5 , 18 .…”

Section: Introductionmentioning

confidence: 99%

High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer

et al. 2021

View full text Add to dashboard Cite

Summary Background Forkhead box (FOX) A1 is a potential therapeutic biomarker that has been investigated in various human cancers. Limited data exist about FOXA1 biologic role in epithelial ovarian cancer (EOC). Aim This study assessed FOXA1 immunohistochemical (IHC) expression and evaluated its association with clinico-pathological parameters in EOC including overall and disease-free survivals (OS, DFS) and patient’s outcome. Methods Patient’s socio-epidemiologic, clinical, radiological, laboratory, surgical, and follow-up data were collected. After histopathologic typing, grading and staging, FOXA1 IHC expression was scored in 98 EOC specimens. Clinico-pathological associations were investigated in high-and low-FOXA1 expression groups using appropriate statistical methods. Kaplan-Meier method was used for survival analysis. Results FOXA1 tumor cell nuclear staining was detected in 63.3% of EOC with weak, moderate and strong scores (28.6%, 12.2% and 22.5% respectively). Comparing high- and low-expression groups (34.7% and 65.3% respectively), high FOXA1 was associated with larger tumors, low mean serum CA-125, tumor histopathology (mucinous and low-grade serous), type I EOC, limited tumor’s anatomical extent, absence of nodal or distant metastases and omental nodules, earlier FIGO stages, non-recurrent tumors and survival advantage with longer and OS and DFS (all p ≤ 0.05). Independent predictors of high FOXA1 expression included: omental nodules, tumor’s anatomical extent and tumor’s size (p ≤ 0.001, = 0.046 and = 0.023 respectively). Conclusion FOXA1 is frequently expressed in EOC notably mucinous and low-grade serous carcinomas in association with favorable prognostic clinico-pathological parameters and longer OS and DFS. It likely has a suppressor function in EOC and could be recommended as a prognostic and therapeutic biomarker.

show abstract

“…FOXA1 has recently been highlighted as a potentially useful marker for triple negative breast cancer 13 , and its expression has been suggested to act as a repressor for a subset of basal signature genes 14 . The association of FOXA1 and triple-negative status has not previously been examined in DCIS, and reports thus far have dismissed a role for FOXA1 as a subtype marker for DCIS as no correlation could be seen with protein expression and that of ER 15,16 . Here we also observed that FOXA1 expression does not systematically differ between ER+ and ER-samples, and its reduced expression is only associated with the basal-like TN samples.…”

Section: Resultsmentioning

confidence: 99%

Creating a ‘Timeline’ of ductal carcinoma in situ to identify processes and biomarkers for progression towards invasive ductal carcinoma

Rebbeck

Jian

Bornelöv

et al. 2022

Preprint

View full text Add to dashboard Cite

Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive disease is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients and even within patients. Using gene expression analysis, we have generated a ‘Timeline’ of disease progression, utilising the variability within patients and combining >2,000 individually micro-dissected ductal lesions from 145 patients into one continuous trajectory. Using this Timeline we show there is a progressive loss in basal layer integrity, coupled with two epithelial to mesenchymal transitions (EMT), one early in the timeline and a second just prior to cells leaving the duct. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.

show abstract

Prognostic significance of transcription factors FOXA1 and GATA-3 in ductal carcinoma in situ in terms of recurrence and estrogen receptor status

Cited by 4 publications

References 27 publications

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma

High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer

Creating a ‘Timeline’ of ductal carcinoma in situ to identify processes and biomarkers for progression towards invasive ductal carcinoma

Contact Info

Product

Resources

About