Dynamic changes of miRNA and cancer related proteins (CRPs) expression during neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22099-e22099
Author(s):  
Manal Al-Khanbashi ◽  
Stefano Caramuta ◽  
Adel Al-Ajmi ◽  
Ibrahim Al-Hadabi ◽  
Shiyam Kumar ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
T Test ◽  
Differentially Expressed ◽  
Proximity Ligation Assay ◽  
P Value ◽  
Base Line ◽  
Serum Samples ◽  
Dynamic Changes

e22099 Background: NAC is used in LABC to downsize the primary tumor and eradicate metastases. This study assessed the Dynamic changes of miRNA and CRP expression during NAC with aim to identify molecular biomarkers that may predict outcome. Methods: Tissue, blood and serum samples were collected at four time points from LABC patients undergoing NAC, including time of diagnosis (base line) after 1st and 4th cycle of Adriamycin/cyclophosphamide, and after 4th cycle of Docetaxel (end point). We used microRNA-microarray for tissue samples and Proximity Ligation Assay (PLA) for serum samples to quantify global miRNA expression and 92 CRPs in LABC patients. The miRNA and CRPS were correlated with clinico-pathological features including stage, grade and clinical response.Statistical analysis was performed using Significant Analysis of Microarray ( SAM), Student's t-test, and Pearson's correlation test. Significant p value was defined as p<0.05. Results: Tissue miRNA expression profiling (n=14) revealed 58 miRNA species that were differentially expressed between NAC endpoint and the baseline (FDR < 15%). Reduced miR-21 expression was associated with disease recurrence. Using PLA (n=33) we identified serumosteoprotegerin, MCP-1, Prolactin, Carbonic Anhydrase IX, CXCL10, CD30L and TGF-alpha levels were significantly associated with overall clinical response (t-test, p<0.05). Moreover, Prolactin and Erythropoietin showed significant associations with the stage (t-test, p<0.05), while MMP3, ErbB4, Midkine, Cathepsin D and Prostasin proteins were associated with the recurrence. Analysis is ongoing to determine the dynamic changes of these biomarkers during the NAC. Conclusions: Our study identified specific miRNAs and CRPs that were differentially expressed during NAC in LABC patients which may have clinical significance.

scholarly journals Influence of ABCB1 C3435T gene polymorphisms on tumor response to neoadjuvant chemotherapy in locally advanced breast cancer patients from Northeastern Brazil.

2019 ◽  
Author(s):  
Diego de Aragão Bezerra ◽  
Jose Juvenal Linhares ◽  
Emmanuelle Coelho Noronha ◽  
Kaio César Simiano Tavares ◽  
André Saraiva Leão Marcelo Antunes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced Breast Cancer ◽  
Single Gene ◽  
Locally Advanced ◽  
Northeastern Brazil ◽  
P Value ◽  
Female Population ◽  
C3435t Polymorphism ◽  
Response To Neoadjuvant Chemotherapy

Abstract Background: Breast cancer (BC) is the most common tumor and the leading cause of cancer-related death among the female population worldwide. To evaluate the association between the ABCB1 C3435T single gene nucleotide polymorphisms (SNPs) with the response to neoadjuvant chemotherapy in women with breast cancer. Methods: This study included 32 female patients who received neoadjuvant chemotherapy. The polymorphisms were genotyped through real-time allele-specific polymerase chain reaction (PCR). The statistical analysis was performed using the Fisher's exact test or Pearson's chi-square test in the Statistical Package for Social Sciences (SPSS) version 20.0 software. Results: The genotypes found for the C3435T polymorphism were in Hardy-Weinberg equilibrium and their genotypic distributions were CC= 10 (31.1%), CT= 14 (43.8%), and TT= 08 (25.0%) with χ2: 0.86 and p-value > 0.05. Allele frequencies were C = 0.54 and T = 0.46. There were no significant statistical differences between genotypes considering the response to neoadjuvant chemotherapy and immunohistochemistry; the presence of the T allele was associated with worsen axillary status response to neoadjuvant chemotherapy. Conclusion: No definite association between the presence of C3435T polymorphism and the response to neoadjuvant chemotherapy was observed. Further studies in Brazil involving larger samples will contribute to validating the results of this study. Keywords: Breast cancer; Neoadjuvant Chemotherapy; Polymorphisms; Gene ABCB1

Molecular signatures generated with RNA Isolated from formalin-fixed paraffin-embedded tumor specimens differentiate metastatic and non-metastatic primary breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 614-614
Author(s):  
K. Tanaka ◽  
D. Shimizu ◽  
H. Kuramochi ◽  
J. Cooc ◽  
M. Williams ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathway Analysis ◽  
Locally Advanced ◽  
T Test ◽  
Differentially Expressed ◽  
Cancer Tissue ◽  
Molecular Signatures ◽  
Metastatic Tumors ◽  
Unequal Variance ◽  
Primary Tumors

614 Background: Breast cancer can be either non-metastatic (locally-advanced) or metastatic, with the latter giving rise to a considerably worse prognosis. Because tissue from patients is generally available only as FFPE specimens, we investigated whether distinct molecular “signatures” could be obtained for these breast cancer types using RNA isolated from archival FFPE specimen blocks in gene expression arrays. Methods: FFPE specimens were available from 15 non-metastatic tumors and 12 primary tumors along with their matching metastases. Up to 5 10-micron sections of each were microdissected to isolate areas of tumor tissue. RNA was extracted using a proprietary procedure of Response Genetics, Inc. and was then amplified and labeled. The resulting cRNA was hybridized to the U133 plus 2.0 GeneChip. An unsupervised PCA analysis of the samples resulted in the first principal component separating 2 distinct groups which consisted of the non-metastatic and metastatic tumors. A differentially expressed gene list between metastatic and non-metastatic CRC was determined. These data were also analyzed for differential canonical pathways using Ingenuity Pathway Analysis. Results: Hierarchical clustering analysis segregated locallyadvanced primary tumors and metastatic primary tumors intotwo clusters with distinct gene signatures. A T-test with unequal variance assumption identified 1595 differentially expressed probe sets with FDR (false discovery rate) = 0.005 (p=0.00015). However, comparison of primary tumors with their liver metastases using a paired T-test showed only 18 differentially expressed probe sets at FDR=0.05 and 1019 genes with significance p value ≤ 0.005. Pathway analysis showed significant deregulation of FGF signaling, G2/M DNA damage cell cycle checkpoint, IL-2, IL-4 and EGF signaling between locally advanced and metastatic primary tumors. Conclusion. We have demonstrated the feasibility of identifying metastatic and non-metastatic tumors by microarray analysis using FFPE breast cancer tissue. This result is currently being validated in a separate larger cohort of patients. [Table: see text]

scholarly journals Distinct MicroRNA Profiles in the Perilymph and Serum of Patients With Menière's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew Shew ◽  
Helena Wichova ◽  
Madeleine St. Peter ◽  
Athanasia Warnecke ◽  
Hinrich Staecker
Keyword(s):  
Mirna Expression ◽  
Mrna Translation ◽  
Meniere’S Disease ◽  
Menière’S Disease ◽  
Differentially Expressed ◽  
Meniere's Disease ◽  
Ménière’S Disease ◽  
Menière's Disease ◽  
Serum Samples ◽  
Ménière's Disease

Hypothesis: Menière's disease microRNA (miRNA) profiles are unique and are reflected in the perilymph and serum of patients.Background: Development of effective biomarkers for Menière's disease are needed. miRNAs are small RNA sequences that downregulate mRNA translation and play a significant role in a variety of disease states, ultimately making them a promising biomarker. miRNAs can be readily isolated from human inner ear perilymph and serum, and may exhibit disease-specific profiles.Methods: Perilymph sampling was performed in 10 patients undergoing surgery; 5 patients with Meniere's disease and 5 patients with otosclerosis serving as controls. miRNAs were isolated from the serum of 5 patients with bilateral Menière's disease and compared to 5 healthy age-matched controls. For evaluation of miRNAs an Agilent miRNA gene chip was used. Analysis of miRNA expression was carried out using Qlucore and Ingenuitey Pathway Analysis software. Promising miRNAs biomarkers were validated using qPCR.Results: In the perilymph of patients with Menière's disease, we identified 16 differentially expressed miRNAs that are predicted to regulate over 220 different cochlear genes. Six miRNAs are postulated to regulate aquaporin expression and twelve miRNAs are postulated to regulate a variety of inflammatory and autoimmune pathways. When comparing perilymph with serum samples, miRNA-1299 and−1270 were differentially expressed in both the perilymph and serum of Ménière's patients compared to controls. Further analysis using qPCR confirmed miRNA-1299 is downregulated over 3-fold in Meniere's disease serum samples compared to controls.Conclusions: Patients with Ménière's disease exhibit distinct miRNA expression profiles within both the perilymph and serum. The altered perilymph miRNAs identified can be linked to postulated Ménière's disease pathways and may serve as biomarkers. miRNA-1299 was validated to be downregulated in both the serum and perilymph of Menière's patients.

scholarly journals Hypofractionated radiotherapy in post mastectomy locally advanced breast cancer: a study from a regional cancer center in North East India

2018 ◽  
Vol 6 (12) ◽  
pp. 3942 ◽  
Author(s):  
Mouchumee Bhattacharyya ◽  
Apurba Kumar Kalita ◽  
Partha Pratim Medhi ◽  
Vikas Jagtap ◽  
Rubu Sunku ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Cancer Center ◽  
P Value ◽  
Breast Cancer Patients ◽  
North East India ◽  
Conventional Fractionation ◽  
North East

Background: Adjuvant radiotherapy has increased local-regional and overall survival rates in breast cancer. Conventional fractionation delivering 50-60 Gray (Gy) over 5-6weeks is a standard approach. A shorter duration of hypofractionated treatment will be more convenient for patients and treatment providers if found safe and equally effective.Methods: Around 50 high risk breast cancer patients who underwent mastectomy were enrolled and randomized into the study arms- CF (Conventional Fractionation) Arm (50Gy/25 Fr @ 2 Gy/fraction/day 5 days a week over 5weeks) and HF (Hypo-Fractionation) arm (40.05 Gy/15 Fr @ 2.67 Gy/fraction/day 5 days a week over 3weeks). Treatment related acute and late toxicities, loco-regional recurrence; distant metastasis and survival rates were recorded for comparison.Results: Twenty-five patients were enrolled in each arm with baseline characters well matched. At median follow up of 44 months, OS was 80% in HF arm against 64% in CF arm (p-value: 0.292). HF arm also showed better DFS at 4 years of 76% compared to 64% in CF arm (p-value: 0.411). Although the difference was not significant statistically, the Hazard Ratio of 1.543 (95% CI: 0.549-4.339) for DFS and 1.801 (95% CI: 0.603-5.377) for OS indicated trends towards better outcomes in HF arm in terms of disease control and survival. Acute and late toxicities were also lesser in HF arm, though not statistically significant (all p-values >0.05).Conclusions: In post mastectomy setting, HFRT is comparable to CFRT in terms of safety and efficacy, will be more convenient for patients and care givers and hence can be a routine standard practice.

Analysis of the pathological response to primary chemotherapy in patients with locally advanced breast cancer (LABC) grouped according to ER, PR and HER2 status

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 626-626 ◽  
Author(s):  
L. A. Fernandez-Morales ◽  
E. Dalmau ◽  
S. Martinez ◽  
A. Arcusa ◽  
C. Pericay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Primary Chemotherapy ◽  
Response To Treatment ◽  
Her2 Status ◽  
P Value ◽  
Chi Squared

626 Background: The determination of ER and PR has a considerable importance when evaluating the prognosis and the response to treatment in breast cancer (BC). Assessment of HER2 status is also a standard for the management of BC. Hormone receptors (HR), HER2, and increasingly, genomic profiles distinguish at least four major classes of BC: HER2+; HER2-HR+, which can be divided into two classes, favorable and unfavorable; and basal-like that express neither HER2 nor HR. In the clinical practice is possible to divided BC according to ER, PR and HER2: ER-PR-HER2+, ER-PR-HER2-, ER+PR+HER2-, ER+RP+HER2+; and less frequently ER+PR-HER2-, ER+PR-HER2+, ER-PR+HER2+ and ER-PR+HER2-. In the neoadjuvant setting the pathological complete response (pCR) to primary chemotherapy (PC) is associated to negativity for ER and PR receptors, and in patients (pts) with HER2 + BC, the addition of trastuzumab to PC increasing the rate of pCR. The aims of this study were to determine the pCR of PC with anthracyclines (A) and taxanes (T) in pts with LABC grouped according to ER, PR and HER2 status. Methods: Pts with LABC treated with PC including A and T were grouped according to ER, PR and HER2 status, and the pCR rate were analyzed using the chi-squared test and correlations with a p value of ≤0,05 were considered statistically significant. Results: A total of 103 pts were treated. There were 14.6% of ER-PR-HER2+ BC, 23.3% ER-PR-HER2-, 35.0%ER+PR+HER2-, 8.7% ER+PR+HER2+, 11.7% ER+PR-HER2-, 2.9% ER+PR-HER2+, 1.9% ER-PR+HER2+, and 1.9% ER-PR+HER2-. For the analysis of pCR only 100 pts were included. There were18 pts who achieved a pCR. Of these pts, 9/18 (50.0%) were RE-RP-HER2-, 5/18 (27.8%) ER-PR-HER2+, 3/18 (16.7%) ER+PR+HER2+, and 1/18 (5.6%) ER+PR+HER2- (p≤0.01). The table 1 show the pCR rate for each subgroup of BC. Conclusions: In patients with LABC to group BC according to ER, PR and HER2 status can help to predict pCR to PC. [Table: see text] No significant financial relationships to disclose.

The effect of trastuzumab on pCR in locally advanced HER2-positive breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 286-286
Author(s):  
S. M. Lavasani ◽  
K. I. Pritchard ◽  
A. Kiss ◽  
S. Verma ◽  
F. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Cancer Center ◽  
P Value ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Her2 Breast Cancer ◽  
Baseline Characteristics

286 Background: Neoadjuvant therapy (NAT) is now standard of care for locally advanced breast cancer (LABC). Evidence shows that pathological complete response (pCR) predicts for disease free and overall survival. The pCR rates for LABC vary widely in the literature but prognosis still remains poor for this group of pts. Increases in pCR have been reported in clinical trials with the addition of trastuzumab (T) but these studies have predominantly included operable pts. The aim of this study was to evaluate whether the addition of T to NAT has improved the rates of pCR in HER2+ LABC pts at our center. Methods: Pts from the LABC prospective database at the Sunnybrook Odette Cancer Center in Toronto were included if they had confirmed HER2+ LABC [primary tumors greater than 5cm (T3) with skin or chest wall involvement (T4) or with matted axillary adenopathy (N2)]. Two cohorts of LABC pts, pre-T and post-T groups were compared for baseline characteristics and pCR. Chi square tests and p values were used for comparing proportions. Results: 43 pts were diagnosed between Jan 2002 to Dec 31, 2006 who had HER2+ breast cancer and received NAT without T (pre-T cohort). 17 HER2+ pts were diagnosed with LABC between Jan 1, 2007 to Dec 31, 2009 who received neoadjuvant T (post-T cohort). Baseline characteristics were similar in two cohorts (Table) except more pts in pre-T cohort received neoadjuvant hormonal therapy. The rate of pCR in the pre-T cohort was 9.3% and in the post-T cohort 29% (p value=0.02). Conclusions: The pCR rate dramatically improved in our LABC patients with the addition of T to NAT. The pCR rates still remain lower than in published clinical trials likely reflecting the more advanced nature of LABC in clinical practice. [Table: see text]

Prediction of Thalidomide Response in the Newly Diagnosed Untreated Multiple Myeloma Patients Based on a Panel of Protein Biomarkers

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5018-5018
Author(s):  
Rajpal Rajpal ◽  
Paul Dowling ◽  
Justine Meiller ◽  
Kenneth C Anderson ◽  
Philip Murphy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Statistical Analysis ◽  
Statistical Significance ◽  
Internal Standard ◽  
T Test ◽  
Differentially Expressed ◽  
Clinical Samples ◽  
Newly Diagnosed ◽  
Serum Samples ◽  
2D Dige

Abstract Background: Multiple Myeloma (MM) is an incurable plasma cell malignancy. Recently, there have been major therapeutic advances in the treatment of MM, including the use of immunomodulatory drugs. Thalidomide alone or in combination represents an effective treatment strategy for newly diagnosed, relapsed and refractory MM patients. The identification of novel biomarkers could lead to more effective, individualized therapeutic strategies with improved patient outcomes. Patients, Method & Material: Serum samples of sixteen newly diagnosed multiple myeloma patients, who had had initial treatment with thalidomide based regimens were analyzed. Based on D100 re-staging, 8 responders and 8 non responders to thalidomide were identified. Samples were analysed using 2D-DIGE, a technique based on pre-electrophoretic labelling of samples with one of three spectrally resolvable fluorescent CyDyes (Cy2, Cy3, and Cy5) allowing multiplexing of samples into the same gel. Initially serum samples were immunodepleted, which specifically removes 14 high-abundant proteins representing approximately 94% of total protein mass. This allowed for easier analysis of low abundance proteins, which are more likely to be a source of potential biomarkers. All 2D-DIGE images were scanned and collected on a Typhoon Fluorescent Imager. Pooled samples were used as an internal standard to quantify expression changes with statistical significance. Statistics and quantitation of protein expression were carried out initially using DeCyder Biological Variation Analysis (BVA) software before performing subsequent Extended Data Analysis (EDA). Results: 18 proteins have been identified to be differentially expressed in non-responders compared to responders: 13 were up-regulated and 5 were down-regulated (t-test ≤ 0.02). All 18 proteins were &gt;1.25-fold differentially expressed, with changes up to 6.62-fold. For example, Fig.1 shows statistical analysis of protein 1 using DeCyder BVA software. This protein was increased 2.24-fold in the immuno-depleted serum from non-responders compared to responders, (t-test 0.0046). Once the 18 panel proteins were established, further statistical analysis was performed using DeCyder EDA software. Principal Components Analysis (PCA) was used to separate the responders from the non-responders based on the panel of 18 statistically significant differentially expressed proteins (Fig.2). Each dot on this plot represents a clinical sample; clinical samples from the same experimental groups are located in the same distinct areas, i.e. contained in one half of the plot, confirming consistency of results. Conclusion: Accurate prediction of an individual patient’s drug response is an important prerequisite of personalized medicine. Using a panel of proteomic biomarkers, we have demonstrated the feasibility of predicting sensitivity and response to thalidomide in previously untreated myeloma. We are in the process of identification of theses proteins and plan to confirm their predictive value in a larger group of patients. Figure Figure Figure Figure

Residual cancer burden (RCB) is practical and may be more informative than pathological response following neoadjuvant chemotherapy (NC) for locally advanced breast cancer (LABC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21103-21103
Author(s):  
D. Sivasubramaniam ◽  
R. Komrokji ◽  
S. Dhaliwal ◽  
V. Sundarajan ◽  
Z. Nahleh
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Cox Regression ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathological Response ◽  
P Value ◽  
Cox Regression Analysis

21103 Background: Complete pathological response (pCR) has been considered a reliable endpoint to assess the benefit of NC. However, different pathological responses ranging from near complete response to resistance would likely indicate different prognostic groups. Method: We studied patients with locally advanced breast cancer (LABC) who received NC between 2001–2006 at the University of Cincinnati. Pathological response to therapy was evaluated. In addition, RCB was quantified according to MD Anderson RCB Calculator index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We examined the correlation between pCR, RCB, event-free survival (EFS) and over all survival (OS) by Cox regression analyses. Result: Pathological slides of 32 patients were analyzed. Median age 52, 38% white and 62% African American. Stage IIB 12% , Stage IIIA 19%, Stage IIIB 53% and Stage IIIC 16% . 72% invasive ducal, 6% invasive lobular and 22% inflammatory cancer. Forty seven percent of tumors were ER +/or PR+ , 53% ER-/PR-, 28% HER-2 /neu + ( IHC 3+ or FISH HER2 gene to chromosome 17 ration > 2.2). Tumor response was as follows: 22% (n=7) achieved pCR , RCB scores ranged between 0- 4.87. By univariate Cox regression analysis, RCB correlated with EFS {Hazard ratio (HR) 1.57 (95% CI 1.04–2.38), p-value 0.018}, and with OS {HR 1.74 (95% CI 0.91 -3.32), p value-0.09}. However, pCR did not seem to correlate with EFS {HR 0 .24 (95%CI 0.03 -1.86–2.38), p-value .172} or OS {HR 0.03 (95% CI 0–89),p value-0.40}. By multivariate Cox regression analysis, RCB was noted to be an independent predictive variable for EFS {HR 1.59 (95% CI 1.04–2.43), p value-0.033} while pCR was not {HR 0.90 (95% CI 0.52–1.57), p value-0.7. Conclusion: RCB was easily quantifiable and appears to be a better predictor of outcome following neoadjuvant chemotherapy in LABC compared to pCR. Higher RCB scores were associated with higher EFS and lower rate of OS. Prospective trials are needed to further evaluate the role of RCB as an endpoint following NC. No significant financial relationships to disclose.

A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 176-176 ◽  
Author(s):  
Gregory M. Heestand ◽  
James Don Murphy ◽  
Jennifer Moughan ◽  
William Regine ◽  
Jia Luo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Free Survival ◽  
High Sensitivity ◽  
Serum Levels ◽  
Proximity Ligation Assay ◽  
P Value ◽  
Serum Samples ◽  
Multivariate Statistical ◽  
Baseline Serum ◽  
Clinical Endpoints

176 Background: RTOG 9704 was an adjuvant pancreatic adenocarcinoma trial. Patients with resected stage I-III disease were randomized to receive 5-FU vs. gemcitabine (GEM) chemotherapy pre and post 5-FU chemoradiation. Prior to adjuvant therapy, patients had baseline serum samples drawn and archived for future study. Methods: To better understand the biology of pancreatic cancer, investigators involved with this project have evaluated numerous proteins of interest via literature review and gene expression data. By using the multiplex capabilities and high sensitivity detection of the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies capable of quantifying 42 key proteins from 24 uL of patient serum. To determine if any of these proteins corresponded with survival or predicted response, the baseline serum specimens were obtained for assay with our PLA panel. Clinical endpoints were overall (OS) and disease-free survival (DFS). Univariate and multivariate statistical techniques were used. Using a Bonferroni correction, a p-value of <0.0012 was considered statistically significant. Results: Of the 451 eligible patients, 213 had samples available for study – 112 (53%) in the 5-FU arm and 101 (47%) in the GEM arm. As expected, decreased levels of CEA and CA 19-9 were prognostic for improved OS in all patients. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an OS benefit from adjuvant GEM, but not 5-FU. Conclusions: PLA is a powerful tool for identifying potential biomarkers from archived, small volume serum samples. These data suggest that pancreatic cancer patients with low MMP-7 serum levels were most likely to benefit from adjuvant GEM. Supported by RTOG grants U10 CA21661, CCOP grant U10 CA37422, and RTOG Biospecimen Resource grant U24 CA114734 from the National Cancer Institute. [Table: see text]

Expression of PDL1 (B7-H1) before and after neoadjuvant chemotherapy (NAC) in urothelial carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 313-313 ◽  
Author(s):  
Ajjai Shivaram Alva ◽  
Andrew McDaniel ◽  
Tianyu Zhan ◽  
Hong Xiao ◽  
Arul M. Chinnaiyan ◽  
...  
Keyword(s):  
Residual Disease ◽  
Locally Advanced ◽  
Staining Intensity ◽  
T Test ◽  
Wilcoxon Test ◽  
P Value ◽  
Combination Strategies ◽  
Before And After ◽  
Residual Tissue ◽  
The Impact

313 Background: Expression of the co-stimulatory ligand PDL1 (B7-H1) of the PD-PDL immune checkpoint on tumor cells enables evasion of anti-tumor immunity. The PD-PDL checkpoint is a therapeutic target in UC. We sought to characterize the impact of cytotoxic NAC on PDL1 expression before and after NAC to inform optimal sequencing/combination strategies of immune/cytotoxic therapies. Methods: Immunohistochemical (IHC) staining for PDL1 was performed using a murine anti-B7-H1 monoclonal antibody (clone 5H1) on a tissue microarray with matched pre-NAC T1/T2 transurethral resection (TURBT) samples (T0=2; Tx=1; T1=1; T2=23, T3=11; T4=2) and post-NAC cystectomy samples (pT0N0=15, TisN0=1, T1N0=3, T2N0=6, T3N0=9, T3Nx=1, T4Nx=1, T2N1=1, T3N2, T4N2=1, T3N3=1) from 40 patients (pts) treated from 1999-2011 at the University of Michigan. NAC was cisplatin-based in 13 pts and carboplatin-based in 26 pts. IHC was scored as the product of tumor cell staining intensity (0-3) and percentage of cells positive (0-100). Correlations of T stage at TURBT with the score were analyzed with unpaired t-test and Wilcoxon test. ANOVA analysis and paired t-tests were done to correlate pStage with the score. Results: PDL1 expression was significantly higher in post-NAC cystectomy specimens (mean IHC product score= 217.5) compared to the matched pre-NAC TUR specimens (mean IHC product score= 176.6, p value=0.0196 by Student's paired T test). Among the 21 non-pT0 pts with data at both time-points, PDL1 expression increased after NAC in 16 pts. The % of PDL1 positive cells in the residual tissue increased in 15 pts. The PDL1 expression product score in pre-NAC or post-NAC tissue did not correlate with clinical or pathologic stage, or with recurrence-free or overall survival. Conclusions: PDL1 expression in locally advanced UC in pts receiving NAC did not correlate with clinical outcomes in our small cohort. However, the expression of PDL1 in post-NAC tissue was elevated compared to pre-NAC. The increased PDL1 expression following NAC informs rational combinations and sequencing of cytotoxic chemotherapy with anti-PD1/PDL1 immunotherapies in UC particularly in adjuvant therapy for residual disease after neoadjuvant therapy.

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