scholarly journals Concordance of folate receptor-α expression between biopsy, primary tumor and metastasis in breast cancer and lung cancer patients

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 17442-17454 ◽  
Author(s):  
Leonora S.F. Boogerd ◽  
Martin C. Boonstra ◽  
Ann-Jean Beck ◽  
Ayoub Charehbili ◽  
Charlotte E.S. Hoogstins ◽  
...  
2016 ◽  
Vol 11 ◽  
pp. BMI.S35075 ◽  
Author(s):  
Daniel J. O'Shannessy ◽  
Darren W. Davis ◽  
Kenna Anderes ◽  
Elizabeth B. Somers

This study describes our efforts to further the field of noninvasive diagnostics, specifically in the area of liquid biopsies in oncology. We employed laser scanning cytometry using highly selective antibodies to interrogate circulating tumor cells (CTCs) that were isolated using ApoStream® technology to identify folate receptor alpha (FRα)–positive cells. We demonstrate that FRα+ CTCs can be isolated from patients with metastatic cancers, including NSCLC adenocarcinoma, breast cancer, and ovarian cancer, whereas squamous cell lung cancer and normal healthy controls were devoid of FRα+ CTCs. We believe that the developed methodology will have applications in both the diagnosis and the monitoring of FRα-expressing cancers. Folate receptor alpha (FRα) expression may have utility as a potential diagnostic and therapeutic target in solid tumors. As tissue samples are not always available for patient screening, this study evaluated a noninvasive assay in CTCs from blood samples to detect FRα expression. The presence of FRα+ CTCs enriched using ApoStream® and detected using laser capture cytometry was evaluated in blood samples from cancer patients [NSCLC adenocarcinoma ( n = 14), breast cancer ( n = 20), ovarian cancer ( n = 6), and squamous lung cancer patients ( n = 6)] and healthy subjects ( n = 20). The data demonstrated that FRα+ CTCs were detected in blood from NSCLC adenocarcinoma, breast, and ovarian cancer patients, whereas squamous cell lung cancer patients and normal healthy controls lacked FRα+ CTCs as previously known. We demonstrate that CTCs captured using ApoStream® can be used to detect FRα+ CTCs and may have clinical utility as a real-time liquid biopsy for assessing FRα levels in cancer patients.


2018 ◽  
Author(s):  
Jonathan P Rennhack ◽  
Matthew Swiatnicki ◽  
Yueqi Zhang ◽  
Caralynn Li ◽  
Evan Bylett ◽  
...  

AbstractMouse models have an essential role in cancer research, yet little is known about how various models resemble human cancer at a genomic level. However, the shared genomic alterations in each model and corresponding human cancer are critical for translating findings in mice to the clinic. We have completed whole genome sequencing and transcriptome profiling of two widely used mouse models of breast cancer, MMTV-Neu and MMTV-PyMT. This genomic information was integrated with phenotypic data and CRISPR/Cas9 studies to understand the impact of key events on tumor biology. Despite the engineered initiating transgenic event in these mouse models, they contain similar copy number alterations, single nucleotide variants, and translocation events as human breast cancer. Through integrative in vitro and in vivo studies, we identified copy number alterations in key extracellular matrix proteins including Collagen 1 Type 1 alpha 1 (Col1a1) and Chondroadherin (CHAD) that drive metastasis in these mouse models. Importantly this amplification is also found in 25% of HER2+ human breast cancer and is associated with increased metastasis. In addition to copy number alterations, we observed a propensity of the tumors to modulate tyrosine kinase mediated signaling through mutation of phosphatases. Specifically, we found that 81% of MMTV-PyMT tumors have a mutation in the EGFR regulatory phosphatase, PTPRH. Mutation in PTPRH led to increased phospho-EGFR levels and decreased latency. Moreover, PTPRH mutations increased response to EGFR kinase inhibitors. Analogous PTPRH mutations are present in lung cancer patients and together this data suggests that a previously unidentified population of human lung cancer patients may respond to EGFR targeted therapy. These findings underscore the importance of understanding the complete genomic landscape of a mouse model and illustrate the utility this has in understanding human cancers.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5904-5904
Author(s):  
Ankit Shah ◽  
Stuthi Perimbeti ◽  
Sumera Bukhari ◽  
Michael Wismer ◽  
Jordan Senchak ◽  
...  

Abstract Background: Febrile neutropenia is associated with significant morbidity, mortality, healthcare resource utilization and associated cost. However, data regarding the relationship of specific cancers with admission for febrile neutropenia and their outcomes is lacking. Methods: Using the ICD-9 codes 288.00 and 288.04, we identified all adult admissions with primary diagnosis of febrile neutropenia during the interval of 2006-2013 from the Nationwide Inpatient Sample (NIS). Hospitalization information regarding mortality rates, length of stay and total charges was extracted for each year. Total cost was adjusted for inflation using data from the U.S. Bureau of Labor Statistics. Differences in these variables in teaching and nonteaching institutions were evaluated. ICD-9 codes for esophageal, colon, rectal, liver, pancreatic, bladder, prostate, cervical, renal, thyroid, lung, and melanoma skin cancers were selected and the percentage of admissions attributed to each malignancy was determined. Results: We identified 48,253 admissions (weighted N = 233,116) with a primary diagnosis of febrile neutropenia from 2006-2013. Most of these admissions occurred at teaching institutions (n=28,902, weighted n=139,574). In-hospital mortality rates for febrile neutropenia had a downward trend over the time period of 2006-2013 although the difference was not statistically significant (p=.082). Specifically, the in-hospital mortality rate was 2.73% in 2006 and 1.35% in 2013. Mean length of stay (days) has decreased from 5.67 (±.16) in 2006 to 5.32 (±0.06) in 2013 (p=.0001) while total charges have increased from $29,113 (±1089) in 2006 to $41,713 (±726) in 2013 (p=.0001). This is greater than the expected inflationary change from $29,133 to $33,641 over the same time period. Mean length of stay (days) was found to be higher at teaching (5.89±.03) than at non-teaching (5.25±.04) hospitals (p=.0001). Similarly, mean total charges were higher in teaching ($41,577±364) than in non-teaching ($34,176±345) institutions (p=.0001). When comparing teaching vs. non-teaching institutions, in-hospital mortality was not found to have a statistically significant difference (p=.2688). Of the 13 malignancies queried, lung cancer (11.06%) and breast cancer (8.40%) accounted for more admissions for febrile neutropenia than the other malignancies selected. Breast cancer (3.62%, p=.0001) and lung cancer (16.11%, p=.0001) were also associated with much higher in-hospital mortality rates compared with the other malignancies selected. Conclusions: Breast and lung cancer account for a significant number of admissions for febrile neutropenia, which is consistent with their national prevalence. Of particular note,breast and lung cancer patients who were admitted for febrile neutropenia had a higher risk of mortality. In lung cancer, the frequently associated smoking-related comorbidities may be contributing to this finding. While in breast cancer, patients with advanced disease have an increase in cumulative lifetime dose of chemotherapy due to prolonged survival and this may result in a weakened bone marrow, a more susceptible patient, and consequently an increase in febrile neutropenia and mortality rates. Thus, given the greater mortality rate and significant number of patients affected, patients with these two malignancies should receive special attention to ensure they receive prophylaxis with granulocyte stimulating agents and/or antibiotics after treatment with cytotoxic chemotherapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17032-17032
Author(s):  
H. Guo ◽  
X. Hu ◽  
Z. Li

17032 Background: To explore the possibility that the standardized uptake value(SUV) of positron emission tomography(PET) could be a prognostic factor for lung cancer and whether it holds more significance than clinical stage,the current predominant prognostic factor for NSCLC patients. To assess the possible connection between the SUV and clinical and histopathologic characteristics of lung cancer patients(especially the histology), in order to build a comprehensive picture for the potential application of SUV. Methods: Eighty-two patients taking PET examination before receiving any treatment were analysed, the majority of which(fifty) consisted of patients treated with multiple modality treatment where surgery played a central role. 1-year and 3-year survival(OS) Rate, Progress Free Survival(PFS) Rate were calculated by Kaplan-Meier method and evaluated with the log-rank test.The prognostic significance was assessed by univariate and multivariate analyses.Nonparametric tests were performed to determine whether there was valuable difference amid each SUV group classified by certain clinical or histopathologic characteristic. Results: A SUV cutoff of 5.0 for the primary tumor showed the greatest discriminative value for overall survival.As for the PFS,the cufoff is 4.0. The SUV for the primary tumor was a significant predictor for both overall survival and PFS, based on the result that the relative risk was 7.075 and 2.719 respectively. As a result of multivariate analyse,the prognostic value of SUV and Clinical Staging was independent of each other, and the value of the SUV was considerably higher than the latter. The SUV for the small-cell lung cancer group was statistically higher than the non-small-cell lung cancer group. And there was significant overall discrepancy across the groups sorted by the degree of differentiation. Conclusions: The SUV of the primary tumor has the potential to be the leading prognostic factor for patients treated by multiple modality treatment, leading to substantially improved management for lung cancer patients. And there could be close connection between SUV and histopathologic or differentiation feature of lung cancer tissue, although it is still open to discussion. Analysis for larger number of cases could settle the issue. No significant financial relationships to disclose.


2020 ◽  
Vol 147 (8) ◽  
pp. 2327-2334 ◽  
Author(s):  
Shinkichi Takamori ◽  
Kazuki Takada ◽  
Mototsugu Shimokawa ◽  
Taichi Matsubara ◽  
Naoki Haratake ◽  
...  

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