FAP-a and GOLPH3 Are Hallmarks of DCIS Progression to Invasive Breast Cancer

Biological markers that could predict the progression of ductal carcinoma in-situ (DCIS) to invasive breast cancer (IDC) are required urgently for personalized therapy for patients diagnosed with DCIS. As stroma was invaded by malignant cells, perturbed stromal-epithelial interactions would bring about tissue remodeling. With the specific expression of the fibroblast activation protein-alpha (FAP-a), Carcinoma-associated fibroblasts (CAFs) are the main cell populations in the remodeled tumor stroma. Golgi phosphoprotein 3 (GOLPH3), a documented oncogene possessing potent transforming capacity, is not only up-regulated in many tumors but also an efficient indicator of poor prognosis and more malignant tumors. The present study aimed to retrospectively evaluate the pathological value of FAP-a and GOLPH3 in predicting the recurrence or progression of DCIS to invasive breast cancer. Immunohistochemical techniques were applied to investigate the expression of FAP-a GOLPH3 in 449 cases of DCIS patients received extensive resection and with close follow-up, but not being treated with any form of chemo- or radio-therapy. The combination of FAP-a and GOLPH3 in predicating the recurrence or progression of DCIS into invasive breast cancer was specifically examined. The study demonstrated that the overexpression of FAP-a in stromal fibroblasts and GOLPH3 in carcinoma cells are highly predictive of DCIS recurrence and progression into invasive breast cancer. Both FAP-a and GOLPH3 have hig...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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Mittal Miller The mechanisms that drive ductal carcinoma in situ (DCIS) progression to invasive cancer are not clear. Studying DCIS progression in humans is challenging and not ethical, thus necessitating the characterization of an animal model that faithfully resembles human disease. We have characterized a canine model of spontaneous mammary DCIS and invasive cancer that shares histologic, molecular, and diagnostic imaging characteristics with DCIS and invasive cancer in women. The purpose of the study was to identify markers and altered signaling pathways that lead to invasive cancer and shed light on early m...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we aimed to evaluate the prognostic significance of CTSV in DCIS. METHODS: CTSV protein expression was immunohistochemically assessed in a well-characterised and annotated cohort of DCIS comprising pure DCIS (n=776) and DCIS coexisting with IBC (n=239). CTSV expression was analysed in tumour cells and surrounding stroma, including its association with clinicopathological parameters and outcome. RESULTS: In pure DCIS, high CTSV expression was observed in 29% of epithelial tumour cells and 20% of surrounding stroma. High expression in both components was associated with features of poor prognosis inc...
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Pathol Source Type: research
ConclusionThis demonstrates procoagulant phenotypic changes occur in fibroblasts at the preinvasive stage. Fibroblast procoagulant phenotype is associated with aggressive breast cancer subtypes and reduced survival. Coagulation may be a therapeutic target in breast cancer.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Mucinous lesions of the breast encompass a range of benign and malignant entities characterized by extracellular mucin production. Increased sampling of mammary calcifications has identified a range of mucocele-like lesions, which are associated with benign proliferative and atypical intraductal epithelial proliferation ranging in architectural complexity from flat epithelial atypia to ductal carcinoma in situ. Mucinous carcinoma is a unique histologic subtype of breast cancer with a good prognosis.
Source: Diagnostic Histopathology - Category: Pathology Authors: Tags: Mini-symposium: Breast Pathology Source Type: research
AbstractThe risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li –Fraumeni syndrome (LFS) or Li–Fraumeni Like (LFL) patients. However, the type ofTP53 pathogenic germline variant may possibly influence this risk.TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenicTP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germlineTP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were follo...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, our WGCNA analysis identified candidate prognostic biomarkers for further basic and clinical researches. Introduction Breast cancer is a frequently diagnosed malignancy and the leading cause of cancer death among females around the world, accounting for 24% of cancer diagnoses and 15% of cancer deaths in females. According to Global Cancer Statistics 2018, there will be nearly 2.1 million new cases diagnosed globally, with ~62 thousand deaths. The incident rates of breast cancer increased in most developing countries during last decades, resulting from a combination of social and economic factors, incl...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: This is the only existing study which has conducted assessment of transcriptional changes associated with TBX3 isoforms (TBX3iso1 and TBX3iso2). Our published study has identified the transcriptional regulator TBX3 as an enabler of EMT in non-high grade, pre-invasive lesions of the breast, inducing SLUG and promoting the transition from in situ (DCIS) to invasive breast cancer.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by array Homo sapiens Source Type: research
Conclusions: This is the only existing study which has conducted assessment of transcriptional changes associated with TBX3 isoforms (TBX3iso1 and TBX3iso2). Our published study has identified the transcriptional regulator TBX3 as an enabler of EMT in non-high grade, pre-invasive lesions of the breast, inducing SLUG and promoting the transition from in situ (DCIS) to invasive breast cancer.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Unlike other ErbB family members, HER2 levels are maintained on the cell surface when the receptor is activated, allowing prolonged signaling and contributing to its transforming ability. Interactions between HER2, HSP90, PMCA2, and NHERF1 within specialized plasma membrane domains contribute to the membrane retention of HER2. We hypothesized that the scaffolding protein ezrin, which has been shown to interact with NHERF1, might also help stabilize the HER2–PMCA2–NHERF1 complex at the plasma membrane. Therefore, we examined ezrin expression and its relationship with HER2, NHERF1, and PMCA2 levels in murine and ...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
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