scholarly journals Expression of ICOSL is associated with decreased survival in invasive breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6903 ◽  
Author(s):  
Bin Wang ◽  
Huayong Jiang ◽  
Tingyang Zhou ◽  
Ning Ma ◽  
Wei Liu ◽  
...  

Background Inducible co-stimulator (ICOS) is a CD28-related molecule exclusively expressed on activated T cells and plays a critical role in modulating the immune response in breast cancer. The blockage of ICOS pathway has been shown to inhibit the activity of Type 2 T helper cells, thus potentially protecting against cancer growth. The current study aims to investigate the correlation between inducible co-stimulator ligand (ICOSL) expression in tumor tissues and the prognoses of patients with invasive breast cancer. Methods Tumor samples from 562 Chinese patients with invasive breast carcinomas were collected between 2003 and 2010. The expression of ICOSL on breast tumor and adjacent non-cancerous tissue was determined via immunohistochemistry. The overall survival (OS) of patients with positive and negative ICOSL expression were described using Kaplan–Meier curves, respectively. Parametric correlation method was used to analyze the correlation between ICOSL expression and other clinicopathological parameters. ICOSL was selected as a dependent variable for multivariate analysis. Results Positive ICOSL expression was identified on the plasma membrane in both cytoplasm and the nucleus of breast cancer cells. Membrane-expressed ICOSL is determined as an independent prognostic factor for OS in breast cancer but without significantly correlating with other clinicopathologic parameters such as age, menopausal status, depth of invasion, lymph node metastasis status, histologic classification, etc. Conclusion Our study suggests that the up-regulated expression of ICOSL protein in breast tumor cells can be associated with poor prognoses in invasive breast carcinomas.

2007 ◽  
Vol 23 (3) ◽  
pp. 189-196 ◽  
Author(s):  
J. Decock ◽  
W. Hendrickx ◽  
M. Drijkoningen ◽  
H. Wildiers ◽  
P. Neven ◽  
...  

Objective:Aberrant expression of individual matrix metalloproteinases has been associated with poor prognosis in various human carcinomas. The current study aimed at defining an RNA expression profile of various MMPs in breast cancer and correlating their expression with clinicopathological parameters.Methods:The RNA expression patterns of 6 MMPs (MMP2, MMP8, MMP9, MMP10, MMP11, MMP13) were determined in 25 breast carcinomas using quantitative RT-PCR and correlated with clinicopathological parameters, including menopausal status, tumor size and grade, and lymph node involvement.Results:We observed high MMP2 levels more frequently in premenopausal than in postmenopausal women (p= 0.02). Analysis of luminal A type invasive ductal carcinomas (19/25), revealed an even stronger association of MMP2 with menopausal status (p= 0.005). Within this subgroup, we also found a correlation between MMP11 and menopausal status (p= 0.02). No correlation was found between MMP expressions and other clinicopathological parameters. In co-expression analyses MMP2-MMP10 and MMP8-MMP9 showed a weak correlation of their expression.Conclusions:Although this is a pilot study, our findings indicate that luminal A invasive ductal carcinomas commonly express high MMP2 and MMP11 levels in premenopausal breast cancer patients and suggest a co-regulation of MMP2-MMP10 and MMP8-MMP9.


2015 ◽  
Vol 21 (3) ◽  
pp. 646-654 ◽  
Author(s):  
Tijana Vujasinovic ◽  
Jelena Pribic ◽  
Ksenija Kanjer ◽  
Nebojsa T. Milosevic ◽  
Zorica Tomasevic ◽  
...  

AbstractOwing to exceptional heterogeneity in the outcome of invasive breast cancer it is essential to develop highly accurate prognostic tools for effective therapeutic management. Based on this pressing need, we aimed to improve breast cancer prognosis by exploring the prognostic value of tumor histology image analysis. Patient group (n=78) selection was based on invasive breast cancer diagnosis without systemic treatment with a median follow-up of 147 months. Gray-level co-occurrence matrix texture analysis was performed retrospectively on primary tumor tissue section digital images stained either nonspecifically with hematoxylin and eosin or specifically with a pan-cytokeratin antibody cocktail for epithelial malignant cells. Univariate analysis revealed stronger association with metastasis risk by texture analysis when compared with clinicopathological parameters. The combination of individual clinicopathological and texture variables into composite scores resulted in further powerful enhancement of prognostic performance, with an accuracy of up to 90%, discrimination efficiency by the area under the curve [95% confidence interval (CI)] of 0.94 (0.87–0.99) and hazard ratio (95% CI) of 20.1 (7.5–109.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the models are generalizable. Whereas further validation is needed on an external set of patients, this preliminary study indicates the potential use of primary breast tumor histology texture as a highly accurate, simple, and cost-effective prognostic indicator of distant metastasis risk.


Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.


Breast Care ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. 171-175
Author(s):  
Frederik Cuperjani ◽  
Lumturije Gashi ◽  
Fisnik Kurshumliu ◽  
Shemsedin Dreshaj ◽  
Fitim Selimi

Background: The aim of this study was to investigate the immunohistochemical expression of ribosomal protein (RP) S6-pS240 in non-special type invasive breast cancer in relation to other prognostic markers and gain new insights to facilitate more individualized treatment. Methods: The following clinical and histopathological parameters of 120 patients were determined: S6-pS240 expression, age, menopausal status, tumor size and grade, TNM stage, Nottingham Prognostic Index (NPI), lymph node stage, estrogen and progesterone receptor (ER/PR) expression, HER2/neu amplification, lymphovascular invasion, and proliferative index as measured by Ki-67. Treatment protocol and disease-free survival were evaluated accordingly. Results: Significant positive correlations were seen between S6-pS240 expression and Ki-67 values (rho = 0.530, p < 0.001), and NPI (rho = 0.370, p < 0.001) and HER2/neu amplification (rho = 0.368, p < 0.001). A negative correlation was found between S6-pS240 and ER/PR expression (rho = 0.362, p < 0.001). Patients with negative RP S6-pS240 expression had significantly longer disease-free survival (log-rank test, p = 0.005). Conclusion: Immunohistochemical analysis of RP S6-pS240 is a valuable additional prognostic marker in patients with invasive breast cancer. Routine use of S6-pS240 immunohistochemistry is recommended.


2019 ◽  
pp. 10-13

Invasive ductal carcinoma (IDC) is the most common histopathological type of breast cancer, accounting for up to 85% of all invasive breast carcinomas [1]. It spreads usually to the bone first. Solitary metastasis is commonly located in the lung, liver or brain [2]. Adrenal glands locations are extremely rare [3]. We report a case of isolated metachronous right adrenal metastasis, diagnosed four years after breast IDC management. The aim is to highlight clinical, diagnostic and therapeutic characteristics of this entity.


Author(s):  
Nicholas M. Gunn ◽  
Mark Bachman ◽  
Edward L. Nelson ◽  
G.-P. Li

Rationally designed, individualized therapeutic strategies have long been a desired objective for breast cancer patients and clinicians as an estimated 178,480 new cases of invasive breast cancer will be diagnosed among women in the United States this year and over 40,000 women are expected to die from the disease. [1] The increasing appreciation of breast tumor cellular heterogeneity raises fundamental questions as to the relative contributions of cellular subsets to the biologic behavior of an individual patient’s tumor. [2] As such, it has become increasingly clear that in many cases, an individualized strategy for the treatment of breast cancer would be of great benefit, and that the ability to isolate relevant cellular subsets from the main tumor population is one of the critical limits to accomplishing this goal.


2008 ◽  
Vol 23 (3) ◽  
pp. 154-160 ◽  
Author(s):  
A. Ribeiro-Silva ◽  
J.P. Oliveira da Costa ◽  
S. Britto Garcia

Osteopontin (OPN) is a secreted, calcium-binding phosphorylated glycoprotein involved in several physiological and pathological events such as angiogenesis, apoptosis, inflammation, wound healing, vascular remodeling, calcification of mineralized tissues, and induction of cell proteases. There is growing interest in the role of OPN in breast cancer. In an attempt to obtain new insight into the pathogenesis of OPN-associated breast carcinomas, an immunohistochemical panel with 17 primary antibodies including cytokeratins and key regulators of the cell cycle was performed in 100 formalin-fixed paraffin-embedded samples of invasive breast carcinomas. OPN was expressed in 65% of tumors and was negatively correlated with estrogen (p=0.0350) and progesterone (p=0.0069) receptors, but not with the other markers and clinicopathological features evaluated including age, menstrual status, pathological grading, tumor size, and metastasis. There was no correlation between OPN expression and carcinomas of the basal-like phenotype (p=0.1615); however, OPN correlated positively with c-erbB-2 status (p=0.0286) and negatively with carcinomas of the luminal subtype (p=0.0353). It is well known that carcinomas overexpressing c-erbB-2 protein have a worse prognosis than luminal tumors. Here, we hypothesize that the differential expression of OPN in the first subtype of carcinomas may contribute to their more aggressive behavior.


2009 ◽  
Vol 69 (8) ◽  
pp. 3634-3641 ◽  
Author(s):  
Chien-Jui Cheng ◽  
Yuh-Charn Lin ◽  
Ming-Tzu Tsai ◽  
Ching-Shyang Chen ◽  
Mao-Chih Hsieh ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1530-1530
Author(s):  
Jiaojiao Zhou ◽  
Kun Zhang ◽  
Xuan Zhu ◽  
Mei Deng ◽  
Meng Luo ◽  
...  

1530 Background: PALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene, which plays a critical role in genome maintenance via interacting with BRCA1/2 and RAD51 when DNA break. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. Therefore, we assessed the mutational frequency, spectrum and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank, to verify the utility of PALB2 genetic testing in Chinese population. Methods: We examined Chinese breast cancer cases (n = 2279) who agreed to participate in research DNA banking, recruited from 1990 through 2016. To identify the mutations, complete coding sequence and intron–exon boundaries of PALB2 were screened with Next Generation Sequencing. Personal and family histories were synchronously collected for mutation identification. Results: Among the 2279 breast cancer patients, 307 patients were familial breast cancer cases and the rest 1972 patients were sporadic breast cancer cases. PALB2 mutation carriers accounted for 7.8% (n = 24) and 4.8% (n = 95) in familial and sporadic breast cancer cohort separately. In total, 31 missense, 4 nonsense, 3 frameshift, 3 splicing and 1 codon mutations of PALB2 were identified in this study. Among the pathologic variants, PALB2 c.1744C > T, c.2748+1G > A, c.2749-1G > C, c.3114-1G > A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, a total of 6 potential damaging missense variants were novelly found in this study, among which the PALB2 c.3035C > T was detected in both sporadic and familial breast cancer. Conclusions: Our data presents the germline mutation status of PALB2 in Chinese patients with breast cancer, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, this information may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation.


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