scholarly journals Chasing Hippos: Implications of YAP1 and TAZ Expression in Pregnancy-Associated Breast Cancer Tumorigenesis

Author(s):  
Anastasios Kyriazoglou ◽  
Anna-Maria Korakiti ◽  
Alkistis-Maria Papatheodoridi ◽  
Kleoniki Apostolidou ◽  
Afroditi Nonni ◽  
...  

Abstract Background: Hippo signaling pathway de-regulation has been strongly associated with tumorigenesis, metastasis, and drug resistance. Pregnancy-associated breast cancer, the most frequently diagnosed malignancy during gestation, demonstrates an intricate molecular nature. The aim of the present study is to evaluate Hippo pathway transducers TAZ and YAP1 expression in pregnancy-associated breast cancer in relation to the clinicopathological characteristics of the disease.Methods: Formalin-fixed paraffin-embedded tissues from 21 PABC patients treated at Alexandra Hospital in Athens, Greece were immunohistochemically analyzed. Statistical analysis was performed to investigate a possible correlation among the Hippo pathway signaling and the clinical features of the disease.Results: In 48% of patients included in the study strong nuclear TAZ/YAP1 staining in tumor cells was identified. Additionally, the hormone receptor negative status was statistically correlated with strong positivity of the TAZ/YAP1 co-transcriptional factors. No association was observed with the overall-survival and the disease-free survival rate. Conclusions: Hippo pathway is proven to be de-regulated in a subset of pregnancy-associated breast cancer patients highlighting the complex molecular background of the disease which certainly requires further investigation.

2020 ◽  
Author(s):  
Mahmoud Al-Masri ◽  
Tawfiq Al-Shobaki ◽  
Hani Al-Najjar ◽  
Rafal Iskanderian ◽  
Enas Younis ◽  
...  

Abstract Introduction BRAF V600E is one of the most common mutations in Papillary Thyroid Cancer (PTC). Its clinical correlation has been extensively studied with contradictory results. The aim of this study is to evaluate the oncological impact of BRAF V600E mutation on a cohort of Middle Eastern PTC patients treated at a single institute.Methods Patients with histologically confirmed PTC that were treated surgically between 2006 to 2015 were included in the study. Formalin fixed paraffin embedded tumor blocks were sectioned and tested for BRAF V600E mutation. Short- and long-term oncological outcomes were collected. Results 128 patients (68% females) were included with a mean age of 38 years (±13.8). Median follow-up was 50 months. BRAF V600E mutation was found in 71% of patientsIThe BRAF negative tumors were significantly larger than the BRAF positive (3.47 cm versus 2.31 cm respectively, P = 0.009). All other clinicopathological characteristics were comparable between BRAF V600E mutation positive and negative groups. The two groups showed similar 5-year Disease-free (P= 0.37) and Overall survival rates (P = 0.94).Conclusion BRAF V600E mutation did not affect loco-reginal recurrence, distant metastasis, overall and disease-free survival. These results support the diversity of BRAF V600E significance among various ethnicities.


PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0123194 ◽  
Author(s):  
Valeria Musella ◽  
Maurizio Callari ◽  
Eleonora Di Buduo ◽  
Manuela Scuro ◽  
Matteo Dugo ◽  
...  

2021 ◽  
Author(s):  
Katsuhisa Enomoto ◽  
Satsuki Fukumoto ◽  
Satoshi Mori ◽  
Fumi Nozaki ◽  
Yukiko Hara ◽  
...  

Abstract Background: Surgical treatment of breast cancer patients aged 85 years or older is still controversial. Methods: A series of surgically treated breast cancer patients aged 85 years or older was evaluated. The clinicopathological features and outcomes of these patients were compared with the features and outcomes of breast cancer patients in the same age group who were managed without surgery. Results: A total of 45 patients (75%) received surgical treatment, and 15 patients (25%) were managed without surgery. The differences between ages, tumor status, nodal status, stage and immunopathological status of the patients undergoing and not undergoing surgery were not significant. Significantly more patients treated by surgery underwent systemic treatment than patients managed without surgery (P=0.004). The three-year disease-free survival rate of patients treated by surgery was higher than that of the patients managed without surgery (90.6% vs 67.5%, respectively; P<0.001).Conclusions: The surgical treatment of breast cancer patients aged 85 years or older is warranted. This outcome was achieved with the use of hormonal therapy.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22212-e22212
Author(s):  
J. Rodgers ◽  
C. Murray ◽  
N. Leaves

e22212 Background: PI3Kinase is an important target for new oncology therapies, since it is central to several cell signalling pathways associated with proliferation and survival. Many pharmaceutical companies have PI3K inhibitors in their drug development pipelines all of which are in early phase trials. Activating mutations in exons 9 and 20 of the PI3KCA oncogene have been observed in a number of important cancer types including: gastrointestinal, breast, liver, lung and genito-urinary cancers. The presence of such mutations may prove useful as companion diagnostic biomarkers for prediction of response to therapy. Methods: Source BioScience (Nottingham, UK) tested three different methods for the detection of PI3K mutations in archival tumour samples, in their CPA and GLP accredited laboratories. Eighty formalin-fixed paraffin-embedded (‘FFPE') samples from histologically confirmed breast cancer samples were tested by the new DxS P13K Mutation Test Kit using real-time PCR, by pyrosequencing (Qiagen), and by conventional bidirectional capillary sequencing. Tumour content was evaluated by pathology review. Results: The results of the comparison showed that the DxS test using rtPCR technology was easy to perform, convenient and robust. The DxS test had a high degree of sensitivity provided there was more than 20% tumour content in the test sample as determined by histology and pathology review. Conclusions: In conclusion, the DxS test is a valuable tool for detecting PI3K mutations in FFPE samples from breast cancer patients. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12018-e12018
Author(s):  
Mustafa Karaca

e12018 Background: Our goal was to compare clinicopathological characteristics and DFS time among breast cancer patients diagnosed with mammography or symptoms. Methods: This was retrospective analysis of 828 patient files. Diagnosis was done with mammography or symptom,considering the followings:age,menopause,hormone and HER2 receptor,grade,histologic subtype,lymphovascular(LVI) and perineuronal invasion(PNI),adjuvant chemotheraphy,adjuvant herceptin,adjuvant hormone and adjuvant radiotheraphy use.Recurrence dates,locations and last appointment dates were noted. Results: Breast cancer was detected by mammography in 324 patients vs by sysmptom in 504.The difference in most cases between these two methods were significant,and respectively:positive ALND 30% vs 53.7% p=0.0001,LVI 13.7% vs 31.6% p=0.0001,PNI 7.2% vs 18.1% p=0.0001,adjuvant chemo 67% vs 85% p=0.0001,adjuvant hormone use 87.3% vs 82% p=0.001.However, recurrence rates did not differ sigificantly among two groups 12% vs 12.6% p=0.4.The median follow-up and DFS time was 48 and 37 months,respectively.Prognostic parameters were also analyzed.Pathologic staging p=0.002,PNI p=0.027,LVI p=0.0001,hormone receptor status p=0.0001,triple negativity p=0.016,luminal A group p=0.048 were found statistically significant on DFS.Diagnosis with mammography was found to have no statistically significant effect on DFS. Conclusions: Although patients diagnosed with mammography had better prognostic parameters,recurrence rates were similar with symptomatic patients at the time of diagnosis.At survival analysis,recurrence rates were calculated to be similar to those of symptomatic patients’ group.


Author(s):  
Valeria Canu ◽  
Sara Donzelli ◽  
Andrea Sacconi ◽  
Federica Lo Sardo ◽  
Claudio Pulito ◽  
...  

AbstractSperm-associated antigen 5 (SPAG5) is an important driver of the cell mitotic spindle required for chromosome segregation and progression into anaphase. SPAG5 has been identified as an important proliferation marker and chemotherapy-sensitivity predictor, especially in estrogen receptor-negative breast cancer subtypes. Here, we report that SPAG5 is a direct target of miR-10b-3p, and its aberrantly high expression associates with poor disease-free survival in two large cohorts of breast cancer patients. SPAG5 depletion strongly impaired cancer cell cycle progression, proliferation, and migration. Interestingly, high expression of SPAG5 pairs with a YAP/TAZ-activated signature in breast cancer patients. Reassuringly, the depletion of YAP, TAZ, and TEAD strongly reduced SPAG5 expression and diminished its oncogenic effects. YAP, TAZ coactivators, and TEAD transcription factors are key components of the Hippo signaling pathway involved in tumor initiation, progression, and metastasis. Furthermore, we report that SPAG5 is a direct transcriptional target of TEAD/YAP/TAZ, and pharmacological targeting of YAP and TAZ severely reduces SPAG5 expression. Collectively, our data uncover an oncogenic feedback loop, comprising miR-10b-3p, SPAG5, and YAP/TAZ/TEAD, which fuels the aberrant proliferation of breast cancer.


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