Clinicopathologic and Prognostic Significance of Transducin-Like Enhancer of Split 1 Protein Expression in Invasive Breast Cancer

Abstract Background KN motif and ankyrin repeat domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumours; however, its role in invasive breast cancer (BC) remains unknown. This study aims to evaluate the clinicopathological and prognostic value of KANK1 expression in operable BC. Methods KANK1 expression was assessed at the transcriptomic level using multiple BC cohorts; the Molecular Taxonomy of BC International Consortium cohort (METABRIC; n = 1980), The Cancer Genome Atlas BC cohort (TCGA; n = 949) and the publicly available BC transcriptomic data hosted by BC Gene-Expression Miner (bc-GenExMiner v4.0) and Kaplan–Meier plotter?. The Nottingham BC cohort (n = 1500) prepared as tissue microarrays was used to assess KANK1 protein expression using immunohistochemistry (IHC). The association between clinicopathological variables and patient outcome was investigated. Results In the METABRIC cohort, high expression of KANK1 mRNA was associated with characteristics of good prognosis including lower grade, absence of lymphovascular invasion and HER2 negativity (all; p < 0.001) and with better outcome [p = 0.006, Hazards ratio, (HR) 0.70, 95% CI 0.54–0.91]. High KANK1 protein expression was correlated with smaller tumour size and HER2 negativity, and better outcome in terms of longer breast cancer-specific survival [p = 0.013, HR 0.7, 95% CI 0.536–0.893] and time to distant metastasis [p = 0.033, HR 0.65, 95% CI 0.51–0.819]. Conclusion These results supported that upregulation of KANK1 works as a tumour suppressor gene in BC and is associated with improved patients’ outcomes.

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Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

Cancers ◽

10.3390/cancers13081952 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1952

Author(s):

Elżbieta Zarychta ◽

Barbara Ruszkowska-Ciastek ◽

Kornel Bielawski ◽

Piotr Rhone

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Stromal Cell ◽

Prognostic Significance ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Roc Curve Analysis ◽

Stromal Cell Derived Factor ◽

A Prospective Study

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

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The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts

Breast Cancer Research and Treatment ◽

10.1007/s10549-016-3709-z ◽

2016 ◽

Vol 156 (1) ◽

pp. 9-20 ◽

Cited By ~ 19

Author(s):

Mohammed A. Aleskandarany ◽

Devika Agarwal ◽

Ola H. Negm ◽

Graham Ball ◽

Ahmed Elmouna ◽

...

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Prognostic Significance

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The prognostic significance of wild-type isocitrate dehydrogenase 2 (IDH2) in breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-019-05459-7 ◽

2019 ◽

Vol 179 (1) ◽

pp. 79-90 ◽

Cited By ~ 3

Author(s):

Abrar I. Aljohani ◽

Michael S. Toss ◽

Sasagu Kurozumi ◽

Chitra Joseph ◽

Mohammed A. Aleskandarany ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Isocitrate Dehydrogenase ◽

Ductal Carcinoma ◽

Tumour Size ◽

Prognostic Significance ◽

Wild Type ◽

Hormonal Receptor ◽

Isocitrate Dehydrogenase 2 ◽

Receptor Negativity

Abstract Background Lymphovascular invasion (LVI) is a prerequisite step in breast cancer (BC) metastasis. We have previously identified wild-type isocitrate dehydrogenase 2 (IDH2) as a key putative driver of LVI. Thus, we explored the prognostic significance of IDH2 at transcriptome and protein expression levels in pre-invasive and invasive disease. Methods Utlising tissue microarrays from a large well annotated BC cohort including ductal carcinoma in situ and invasive breast cancer (IBC), IDH2 was assessed at the transcriptomic and proteomic level. The associations between clinicopathological factors including LVI status, prognosis and the expression of IDH2 were evaluated. Results In pure DCIS and IBC, high IDH2 protein expression was associated with features of aggressiveness including high nuclear grade, larger size, comedo necrosis and hormonal receptor negativity and LVI, higher grade, larger tumour size, high NPI, HER2 positivity, and hormonal receptor negativity, respectively. High expression of IDH2 either in mRNA or in protein levels was associated with poor patient’s outcome in both DCIS and IBC. Multivariate analysis revealed that IDH2 protein expression was an independent risk factor for shorter BC specific-survival. Conclusion Further functional studies to decipher the role of IDH2 and its mechanism of action as a driver of BC progression and LVI are warranted.

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Prognostic Significance of Molecular Profile in Non-metastatic Invasive Breast Cancer: A Multicentre Study from India

Indian Journal of Gynecologic Oncology ◽

10.1007/s40944-020-0381-3 ◽

2020 ◽

Vol 18 (2) ◽

Author(s):

Krishnakumar Rathnam ◽

K. Niraimathi ◽

Hemant Deepak Shewade ◽

Chenappa N. Patil ◽

Neelesh Reddy ◽

...

Keyword(s):

Breast Cancer ◽

Multicentre Study ◽

Invasive Breast Cancer ◽

Prognostic Significance ◽

Molecular Profile

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PR149 PROGNOSTIC SIGNIFICANCE OF KI67 PROTEIN EXPRESSION IN METASTATIC BREAST CANCER SURVIVAL

The Breast ◽

10.1016/s0960-9776(15)30161-2 ◽

2015 ◽

Vol 24 ◽

pp. S73

Author(s):

Natasa Todorovic-Rakovic ◽

Ksenija Kanjer ◽

Zora Neskovic-Konstantinovic

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Protein Expression ◽

Cancer Survival ◽

Prognostic Significance ◽

Metastatic Breast ◽

Breast Cancer Survival

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Prognostic Significance of a Novel Hypoxia-Regulated Marker, Carbonic Anhydrase IX, in Invasive Breast Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.16.3660 ◽

2001 ◽

Vol 19 (16) ◽

pp. 3660-3668 ◽

Cited By ~ 294

Author(s):

Stephen K. Chia ◽

Charles C. Wykoff ◽

Peter H. Watson ◽

Cheng Han ◽

Russell D. Leek ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Breast Carcinoma ◽

Carbonic Anhydrase ◽

Invasive Breast Cancer ◽

Estrogen Receptor Status ◽

Prognostic Significance ◽

Invasive Breast Carcinoma ◽

Carbonic Anhydrase Ix ◽

Ca Ix

PURPOSE: To assess the frequency of expression and the prognostic significance of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of patients with invasive breast cancer. PATIENTS AND METHODS: CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treated with adjuvant hormonal or chemotherapy. The frequency of CA IX expression, its association with recognized prognostic factors, and the relationship with outcome was evaluated by univariate and multivariate statistical analyses. RESULTS: CA IX expression was present in 49 (48%) of 103 cases. The level of CA IX expression was found to be significantly associated with tumor necrosis (P < .001), higher grade (P = .02), and negative estrogen receptor status (P < .001). Furthermore, CA IX expression was associated with a higher relapse rate (P = .004) and a worse overall survival (P = .001). By multivariate analysis, CA IX was also shown to be an independent predictive factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to 6.75, P = .05). CONCLUSION: CA IX expression was associated with worse relapse-free survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.

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