Urokinase-type plasminogen activator gene (PLAU) to predict clinical outcome in invasive lobular carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21010-e21010
Author(s):  
Otto Metzger ◽  
Stefan Michiels ◽  
Sandeep K. Singhal ◽  
François Bertucci ◽  
Christine Desmedt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Likelihood Ratio ◽  
Invasive Lobular Carcinoma ◽  
Prognostic Value ◽  
Lobular Carcinoma ◽  
Disease Free Survival ◽  
Immune Response Gene ◽  
Prognostic Information ◽  
Gene Signatures

e21010 Background: At the molecular level invasive lobular carcinoma (ILC) is mostly composed of luminal A (LA) (≈80%) followed by luminal B (≈15%) and a small fraction of HER2-positive (≈5%) tumors (Metzger et al SABCS2011). In ILC, Genomic Grade (GG) adds prognostic information to clinico-pathological (CP) characteristics (Metzger et al ASCO 2011). In this study we sought to evaluate the prognostic value of different gene signatures/modules in patients diagnosed with LA classic ILC. Methods: Gene expression data were generated from 184 consecutive frozen tumor samples using Affymetrix U133 Plus 2.0 arrays. ILC tumors were classified into molecular subtypes using the PAM50 classifier. ILC tumors characterized as classic ILC by pahtologists and as LA by PAM50 were selected for this analysis. Invasive disease free survival (IDFS) was defined as the interval between date of surgery and date of any invasive recurrence or death. Multivariate analyses for IDFS and overall survival (OS) adjusted for age, tumor size, nodal status and chemotherapy was performed for gene signatures/modules related to proliferation, invasion, immune response and signaling pathways (IGF1, PI3K, MAPK, Src, Wnt). Results: 125 LA classic ILC tumors were identified with a median follow-up of 6.6 years (95% CI 5.6-7.6). The addition of PLAU gene expression as continous variable to CP variables yielded a significant hazard ratio (HR) for IDFS (HR= 2.1 [1.1 – 4.1], Δx2= 4.5, likelihood ratio p = 0.03) and for OS (HR = 3.6 [1.4 – 9.6], Δx2= 6.9, likelihood ratio p = 0.009). GG as a continous variable yielded a significant HR for IDFS (HR= 2.6 [1.2 – 5.7], Δx2= 6.2, likelihood ratio p = 0.01), but not for OS (HR= 2.1 [0.8 – 5.5], Δx2= 2.5, likelihood ratio p = 0.11). In contrast, IGF1, PI3K, MAPK, Src, Wnt, immune response, gene-70 and gene-76 failed failed to add signficant independent prognostic value. Conclusions: In addition to GG, PLAU adds prognostic information to CP factors in LA classic ILC and may guide future drug development in this difficult to treat BC subset. Of interest, PLAU is involved in degradation of extracellular matrix contributing to cell migration and metastasis and is a major component of a validated breast cancer biomarker (UPA/PAI1).

Prognostic value of immune response gene expression in early stage curatively resected NSCLC: Data from the JBR.10 trial.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 8528-8528
Author(s):  
Wolfgang M. Brueckl ◽  
Akin Atmaca ◽  
Salah-Eddin Al-Batran ◽  
Joachim H Ficker ◽  
Ralph M Wirtz
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Prognostic Value ◽  
Early Stage ◽  
Immune Response Gene ◽  
Response Gene ◽  
Resected Nsclc

scholarly journals Clinical quantitation of immune signature in follicular lymphoma by RT-PCR–based gene expression profiling

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4764-4770 ◽  
Author(s):  
Richard J. Byers ◽  
Ebrahim Sakhinia ◽  
Preethi Joseph ◽  
Caroline Glennie ◽  
Judith A. Hoyland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Follicular Lymphoma ◽  
Gene Expression Profiling ◽  
Real Time ◽  
Expression Profiling ◽  
Immune Response Gene ◽  
Routine Practice ◽  
Gene Signatures ◽  
Survival Interval

Abstract Microarray gene expression profiling studies have demonstrated immune response gene signatures that appear predictive of outcome in follicular lymphoma (FL). However, measurement of these marker genes in routine practice remains difficult. We have therefore investigated the immune response in FL using real-time polymerase chain reaction (PCR) to measure expression levels of 35 candidate Indicator genes, selected from microarray studies, to polyA cDNAs prepared from 60 archived human frozen lymph nodes, in parallel with immunohistochemical analysis for CD3, CD4, CD7, CD8, CD10, CD20, CD21, and CD68. High levels of CCR1, a marker of monocyte activation, were associated with a shorter survival interval, and high levels of CD3 with better survival, while immunohistochemistry demonstrated association of high numbers of CD68+ macrophages with a shorter survival interval and of high numbers of CD7+ T cells with a longer survival interval. The results confirm the role of the host immune response in outcome in FL and identify CCR1 as a prognostic indicator and marker of an immune switch between macrophages and a T cell–dominant response. They demonstrate the utility of polyA DNA and real-time PCR for measurement of gene signatures and the applicability of using this type of “molecular block” in clinical practice.

Outcome and immune landscape of HER2-positive invasive lobular carcinoma in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 535-535
Author(s):  
Saranya Chumsri ◽  
Zhuo Li ◽  
Tracy Shachner ◽  
Pooja Advani ◽  
Kostandinos Sideras ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Invasive Lobular Carcinoma ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Lobular Carcinoma ◽  
Categorical Variables ◽  
Lymph Node Status ◽  
Her2 Positive ◽  
Gene Signatures

535 Background: Invasive lobular carcinoma (ILC) is a rarer form of breast cancer, accounting for 10% of the disease cases. HER2 overexpression in ILC is infrequent and limited data exist regarding clinical characteristics and outcome of HER2-positive (HER2+) ILC patients (pts) treated with adjuvant trastuzumab. Methods: Patient characteristics were compared between ILC and invasive ductal carcinoma (IDC) using Wilcoxon rank sum test for continuous variables and Chi-square test for categorical variables. Kaplan-Meier (KM) method was used to estimate the freedom from mortality and recurrence. Cox regression model was used to evaluate the association between ILC and outcomes adjusted for other characteristics. NanoString technology was used to quantify mRNA to develop immune-related gene signatures. Results: From a total of 3,304 pts, 122 (3.7%) pts had ILC. Pts with ILC were significantly older (median age 54 vs. 49 years), had larger tumors, lower grade, more ER and PR positive tumors, and more lymph node involvement (25.4% had N3 disease compared to 12.7% in IDC). Overall, with KM analysis, pts with ILC had significantly worse overall survival (OS, p = 0.005) and recurrence-free survival (RFS, p = 0.046) compared to IDC. The 15-year freedom from recurrence was merely 57.67% in ILC compared to 72.68% in IDC. A significant number of hormone receptor-positive (HR+) ILC pts developed late recurrence with cumulative event rates increasing from 23% at 5 years to 42% at 15 years. Nevertheless, in multivariate Cox regression analysis adjusting for other clinical characteristics, including age, tumor size, grade, ER/PR, and lymph node status, lobular histology was not significantly associated with worse outcome for OS (HR = 1.19, 95%CI 0.67-2.1, p = 0.55) and RFS (HR = 1.5, 95%CI 0.9-2.5, p = 0.12), as compared with IDC. However, ILC pts appeared to have similar degree of benefit from trastuzumab, with RFS HR = 0.58 compared to HR = 0.67 in the entire population. For immune landscape, there was no significant difference in gene signatures related to CD45, CD8, B cells, or cytotoxic cells. However, ILC had more enrichment in mast cell gene signature and fewer macrophage, NK CD56dim, and regulatory T cell signatures compared to IDC (p < 0.05). Conclusions: HER2+ ILC has distinct clinical characteristics and immune landscape compared to IDC. ILC pts appeared to have worse outcome compared to IDC likely because ILC pts often presented with more locally advanced disease. However, similar benefit of trastuzumab was observed in ILC pts. Due to high risk of late relapse in HR+ HER2+ ILC, extended adjuvant endocrine therapy should be considered in this group of high-risk pts. Clinical trial information: NCT00005970.

scholarly journals Limited Dynamic Range of Immune Response Gene Expression Observed in Healthy Blood Donors Using RT-PCR

2006 ◽  
Vol 12 (7-8) ◽  
pp. 185-195 ◽  
Author(s):  
Kevin McLoughlin ◽  
Ken Turteltaub ◽  
Danute Bankaitis-Davis ◽  
Richard Gerren ◽  
Lisa Siconolfi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Donors ◽  
Dynamic Range ◽  
Immune Response Gene ◽  
Rt Pcr ◽  
Response Gene

Modulation of immune response gene expression by echinacea extracts: results of a gene array analysisThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (11) ◽  
pp. 1091-1098 ◽  
Author(s):  
M. Altamirano-Dimas ◽  
J. B. Hudson ◽  
D. Cochrane ◽  
C. Nelson ◽  
J. T. Arnason
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Gene Array ◽  
Immune Response Gene ◽  
Natural Health Products ◽  
Response Gene ◽  
Cytokines And Chemokines ◽  
Biological Responses ◽  
Health Products ◽  
Factor C

Echinacea extracts have traditionally been used in the treatment of many infectious and other diseases (such as rhinovirus colds), and research has revealed the presence of various bioactivities in these extracts, particularly those connected with immune responses. We examined the effects of Echinacea by using gene expression analysis in a line of human bronchial epithelial cells, with or without rhinovirus infection. More than 13 000 human genes were evaluated. From these analyses we focused primarily on immune response genes and found that both Echinacea extracts, one predominantly rich in polysaccharides and the other rich in alkylamides and caffeic acid derivatives, stimulated the expression of numerous genes. These included a number of cytokines and chemokines, although the pattern of stimulation was different. In addition, Echinacea extracts tended to neutralize the effects of the rhinovirus. When the immune response gene pathways were analyzed with the Ingenuity Pathway program, it became apparent that many of them were interconnected through a major node, the transcription factor C/EBPβ (CAAT/enhancer-binding protein β) and its related C/EBP proteins. This suggests that Echinacea can bring about important biological responses in cells by virtue of interactions between components of the extract and a small number of intracellular factors involved in multiple signaling pathways.

Clinical Measurement of Prognostic Immune Signature in Follicular Lymphoma by RT-PCR Based Gene Expression Profiling and Immunohistochemistry Demonstrates Favourable T-Cell and Unfavorable Macrophage Infiltration.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 359-359
Author(s):  
Richard J. Byers ◽  
Ebrahim Sakhinia ◽  
Preethi Joseph ◽  
Caroline Glennie ◽  
Sara McDermott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Image Analysis ◽  
Real Time ◽  
High Power ◽  
Real Time Pcr ◽  
High Power Field ◽  
Gene Signatures ◽  
Expression Levels ◽  
Survival Interval

Abstract Gene expression profiling studies have demonstrated immune response gene signatures predictive of outcome in follicular lymphoma (FL) and there is a need for validation of these signatures and for their translation to clinical use. However, measurement of these genes in routine practice remains difficult and to date there have been very few studies validating the hypothesis. We have previously demonstrated the utility of real-time PCR measurement of gene expression levels in globally amplified polyA cDNA as a clinically practical method for translation of gene signatures to clinical use. In this project we extended the method to analysis of immune response signatures in FL. We used real-time PCR to measure expression levels (normalised to the mean of 4 housekeeping genes) of 36 candidate Indicator genes, selected from microarray studies, in polyA cDNAs prepared using polyA PCR (method detailed in Sakhinia et al 2007) from 58 archived human frozen lymph nodes, together with immunohistochemistry for CD3, CD4, CD7, CD8, CD10, CD20, CD21 and CD68 in parallel formalin fixed paraffin embedded tissue samples to measure immune response in FL. Immunohistochemical positivity was measured by a semi-automated image analysis method using spectral unmixing to identify areas of immunopositivity. Kaplan-Mier survival analysis was performed against the normalised real-time PCR expression levels of each of the genes and against the percentage immunohistochemical postivity for CD3, CD4, CD7, CD8, CD10, CD20, CD21; for CD68 survival analysis was performed for cases with either 15 or less or more than 15 CD68 positive cells per high power field (hpf). High levels of CCR1, a marker of monocyte actication, were associated with a shorter survival interval (p<0.02) (figure 1a), whilst immunohistochemistry demonstrated association of high numbers of CD7 positive T-cells with longer survival interval (figure 1b) (p<0.032) and of high numbers of CD68 positive macrophages with a shorter survival interval (figure 1c) (p<0.02). The results confirm the role of the host immune response in outcome in FL and identify CCR1 as a prognostic indicator and marker of immune switch between macrophage and T-cell dominant response. The methods used are clinically applicable, whilst the clinical utility of polyA DNA and real-time PCR for measurement of gene signatures and the strength of this approach as a “molecular block” are confirmed. Kaplan-Meier Survival Plots for upper (3&4) and lower (1&2) quartiles of a) CCR1 expression and b) number of CD7 +ve cells, and c) cases with less then vs greater than or equal to 15 macrophages per high power field CCR1 measured by real-time PCR and CD7 and macrophage numbers by immunohistochemistry and image analysis Kaplan-Meier Survival Plots for upper (3&4) and lower (1&2) quartiles of a) CCR1 expression and b) number of CD7 +ve cells, and c) cases with less then vs greater than or equal to 15 macrophages per high power field CCR1 measured by real-time PCR and CD7 and macrophage numbers by immunohistochemistry and image analysis

scholarly journals Genomic grade adds prognostic value in invasive lobular carcinoma

2013 ◽  
Vol 24 (2) ◽  
pp. 377-384 ◽  
Author(s):  
O. Metzger-Filho ◽  
S. Michiels ◽  
F. Bertucci ◽  
A. Catteau ◽  
R. Salgado ◽  
...  
Keyword(s):  
Invasive Lobular Carcinoma ◽  
Prognostic Value ◽  
Lobular Carcinoma

Prognostic Value of Coexisting Lobular Carcinoma In Situ With Invasive Lobular Carcinoma

2016 ◽  
Vol 24 (10) ◽  
pp. 738-743 ◽  
Author(s):  
Aparna Harbhajanka ◽  
Ihab Lamzabi ◽  
Sahr Syed ◽  
Richa Jain ◽  
Ritu Ghai ◽  
...  
Keyword(s):  
Invasive Lobular Carcinoma ◽  
Carcinoma In Situ ◽  
Prognostic Value ◽  
Lobular Carcinoma ◽  
Lobular Carcinoma In Situ

scholarly journals Clinicopathological and Molecular Characteristics of Pleomorphic Invasive Lobular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Jennifer M. Segar ◽  
Ritu Pandey ◽  
Kiah J. Farr ◽  
Raymond Nagle ◽  
Lauren LeBeau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Expression Analysis ◽  
Invasive Lobular Carcinoma ◽  
Gene Expression Analysis ◽  
Cellular Proliferation ◽  
Lobular Carcinoma ◽  
Mtor Pathway ◽  
Proliferation Index ◽  
Molecular Characteristics

Pleomorphic invasive lobular carcinoma (PILC) is a distinct morphological and biologically aggressive variant of invasive lobular carcinoma (ILC). We hypothesized that was due to de novo activation of PI3K/Akt/mTOR pathway in PILC resulting in higher proliferation rate and markers of cell cycle activation. We identified PILC and ILC tumors and tested for PI3K/Akt/mTOR pathway activation by immunohistochemistry (PTEN and pS6K1) and gene expression analysis (by Nanostring nCounter system). Proliferation index (Ki67) was elevated in 85% of PILCs compared to 20% of ILCs ( p < 0.007 ). PTEN expression was high in all while pS6K1 was high in 8/9 PILCs compared to 3/9 ILCs ( p < 0.007 ). Gene expression analysis shows that PILCs have overexpression of genes involved in cell cycle proliferation, cellular proliferation, DNA damage, and repair genes but no difference in PI3K/Akt/mTOR pathway genes. PILCs are a biologically distinct group of ILC, and clinicopathological characteristics suggest they would have a more clinically aggressive behavior. In addition, our results indicate that PI3k/Akt/mTOR pathway and cell cycle proliferation are activated in majority of these tumors. Further studies are needed to investigate these mechanisms as there are approved therapies available that may benefit PILCs.

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