Prognostic significance of cathepsin V (CTSV/CTSL2) in breast ductal carcinoma in situ.

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 including higher nuclear grade, hormone receptor negativity and HER2 positivity. In addition, stromal CTSV expression was associated with larger DCIS size, comedo-type necrosis and high proliferation index. DCIS associated with IBC showed higher CTSV expression than pure DCIS either within the epithelial tumour cells or surrounding stroma (p
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Pathol Source Type: research

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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
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
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
AbstractSalivary duct carcinomas (SDC) and Her2/Neu3-overexpressing invasive breast carcinomas (HNPIBC/IBC) are histologically indistinguishable. We investigated whether common histopathologic and immunophenotypic features of SDC and IBC are mirrored by a similar microRNA (miRNA) profile. MiRNA profiling of 5 SDCs, 6 IBCs Her2/Neu3+, and 5 high-grade ductal breast carcinoma in situ (DCIS) was performed by NanoString platform. Selected miRNAs andHOXA1 gene were validated by RT-PCR. We observed similar miRNA expression profiles between IBC and SDC with the exception of 2 miRNAs,miR-10a andmiR-142-3p, which were higher in IBC...
Source: Head and Neck Pathology - Category: Pathology Source Type: research
We examined whether the scaffolding protein sodium-hydrogen exchanger regulatory factor 1 (NHERF1) interacts with the calcium pump PMCA2 and the tyrosine kinase receptor ErbB2/HER2 in normal mammary epithelial cells and breast cancer cells. NHERF1 interacts with the PDZ-binding motif in PMCA2 in both normal and malignant breast cells. NHERF1 expression is increased in HER2-positive breast cancers and correlates with HER2-positive status in human ductal carcinoma in situ (DCIS) lesions and invasive breast cancers as well as with increased mortality in patients. NHERF1 is part of a multiprotein complex that includes PMCA2, H...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
Mixed ductal-lobular carcinomas (MDL) display both ductal and lobular morphology, and are a clear example of intratumour morphological heterogeneity. The evolution of MDL carcinomas is not well understood. There is a paucity of data surrounding the genetic origin of the different morphological compartments and it remains to be seen whether the coincident presentation of these distinct morphological entities represents two independent tumours that have collided (so called 'collision tumours'), or whether they arise from a common clone. We propose that clonal progression during the evolution of these tumours is associated wi...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research
Conclusions: Analysis 15 markers and use of K-means clustering algorithm, shows prominent inter-tumoral (but not intra-tumoral) heterogeneity in DCIS. Furthermore, epithelial cell specific clusters (high HER2 or EGFR) were associated with distinct B or T cell infiltration by TILs. Additional ongoing studies will determine the clinical significance of the clusters with respect to recurrence of DCIS and development of invasive carcinomas.Citation Format: Badve S, Gökmen-Polar Y, Harris AL, Sui Y, Sevinsky C, Santamaria-Pang A, Ginty F, Tan PH, Gerdes MJ. Impact of heterogeneity of DCIS on immune cell infiltrations [abst...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research
Conclusions: This study demonstrated molecular heterogeneity in DCIS; however, similar molecular phenotypes were seen in the coexisting IDC suggesting that DCIS is a precursor lesion and can predict phenotype of the invasive component. This also suggests that the invasiveness of DCIS is not dependent solely on the molecular character of the tumor epithelial cells, but factors such as tumor microenvironment may play a role.
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
More News: Breast Cancer | Breast Carcinoma | Breast Conservation Surgery | Cancer | Cancer & Oncology | Carcinoma | Carcinoma in Situ | DCIS (Ductal Carcinoma in Situ) | Ductal Carcinoma | Epithelial Cancer | HER2 | Hormones | Study