Association between insulin-like growth factor-1 receptor (IGF1R) expression in circulating tumor cells (CTCs) and prognosis in patients with metastatic breast cancer (MBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1086-1086
Author(s):  
Alessandra Gennari ◽  
Rita Zamarchi ◽  
Dino Amadori ◽  
Andrea De Censi ◽  
Oriana Nanni ◽  
...  

1086 Background: CTCs are strongly associated with prognosis in MBC. In a recent metanalysis on 1944 patients, a CTC count > 5/7.5 ml was associated with a 2-fold increased risk of progression and death. Little evidence is available on the prognostic role of phenotypic CTC assessment, however. In this study, nested in a randomized clinical trial of Ist line chemotherapy ± metformin, we evaluated the prognostic role of IGF1R expression in CTCs, given its potential growth promoting effect. Methods: CTCs were isolated from blood samples of enrolled patients; an automated sample preparation and analysis system (CellSearch) was customized for detecting IGF1R positive CTCs. The prognostic role of total CTCs, IGF1R positive (+ve) and negative (-ve) CTCs was assessed by fitting different PFS and OS multivariate Cox’s models.Results: CTC evaluation at baseline was performed in 72 of 126 patients, of whom 30 (42%) had CTCs ≥5/7,5ml and 41 (57%) had at least one IGF1R+ve CTC. In univariate analysis the prognostic role of total CTCs was confirmed: PFS ( < 5 vs ≥5) HR = 1.69, 95%CI 1.01-2.69, p 0.042 and OS HR = 2.80, 95%CI 1.47-5.30, p 0.002).However, when total CTCs were split in IGF1R+ve and IGF1R–ve, a striking difference was seen in the prognostic effect of these cell types.While no association was detected between an increasing number of IGF1R+ve CTCs and PFS or OS (p = 0.56 and p = 0.99), the number of IGF1R-ve CTCs ( < 4 vs ≥4) was strongly associated with an increased risk of progression and death: HR 1.93 (95%CI 1.15-3.23, p 0.013) and 3.65 (95%CI 1.88-7.09, p 0.001). In multivariate analysis, adjusted for metformin, the prognostic role of the number of IGF1R-ve CTCs was confirmed, while no residual prognostic role of total CTCs or number of IGF1R+ve cells was found (p = 0.55 and p = 0.64 for PFS; p = 0.86 in both cases for OS). Conclusions: In our study, the loss of IGF1R expression in CTCs exhibited a significant adverse prognostic effect, whereas no significant effect of total CTCs and IGF1R+ve CTCs was observed. This finding supports the biological characterization of CTCs as a critical step for further definition of their prognostic significance.

2017 ◽  
Vol 27 (4) ◽  
pp. 708-713 ◽  
Author(s):  
Edwina Coghlan ◽  
Tarek M. Meniawy ◽  
Aime Munro ◽  
Max Bulsara ◽  
Colin JR Stewart ◽  
...  

ObjectiveOur objective was to validate the prognostic role of the chemotherapy response score (CRS), which has been proposed for measuring tumor response to neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian carcinoma, in predicting progression-free survival (PFS) and overall survival (OS).MethodsA retrospective cohort study was conducted of patients with advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1, 2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment-related tumor regression was determined according to the 3-tier CRS, and results were compared with standard clinicopathological variables. Survival analysis was performed using Cox proportional hazards models and the log-rank test.ResultsSeventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty-eight patients (82%) had disease recurrence and 32 (45%) had died at study census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3, respectively. On univariate analysis, the CRS significantly predicted PFS (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.83–7.78; P = 0.000) and OS (HR, 2.81; 95% CI, 1.16–6.79; P = 0.022). In a multivariate model, the CRS was significantly associated with PFS (HR, 2.81; 95% CI, 1.16–6.79; P = 0.022) but not with OS (HR, 2.39; 95% CI, 0.47–3.08; P = 0.079). Patients with CRS of 1 and 2 combined were twice as likely to progress during the study period compared with patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06–3.78; P = 0.032; median PFS, 16 vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR, 1.57; 95% CI, 0.68–3.65; P = 0.291).ConclusionsIn this study, the CRS showed independent prognostic significance for PFS but not for OS.


2020 ◽  
Vol 26 (32) ◽  
pp. 3915-3927 ◽  
Author(s):  
Stefano Ballestri ◽  
Claudio Tana ◽  
Maria Di Girolamo ◽  
Maria Cristina Fontana ◽  
Mariano Capitelli ◽  
...  

: Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. : The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. : In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. : Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.


2015 ◽  
Vol 37 (5) ◽  
pp. 1967-1972 ◽  
Author(s):  
Bo Li ◽  
Xin Zhao ◽  
Shumei Li

Background/Aims: The prognostic role of serum procalcitonin level in critically ill patients with ventilator-associated pneumonia was unclear. The aim of our study was to investigate the relationship between serum procalcitonin level and mortality risk in critically ill patients with ventilator-associated pneumonia. Methods: Data of critically ill patients with ventilator-associated pneumonia were retrospectively collected. Demographics, comorbidities, and serum procalcitonin level were extracted from electronic medical records. The primary outcome was mortality within two months after diagnosis. Multivariable Cox regression analyses were performed to assess the prognostic role of serum procalcitonin level in those patients. Results: A total of 115 critically ill patients with ventilator-associated pneumonia were enrolled in our study. Serum procalcitonin level was not associated with age, gender, or other comorbidities. Univariate Cox regression model showed that high serum procalcitonin level was associated increased risk of morality within 2 months after diagnosis (OR = 2.32, 95% CI 1.25-4.31, P = 0.008). Multivariable Cox regression model showed that high serum procalcitonin level was independently associated increased risk of morality within 2 months after diagnosis (OR = 2.38, 95% CI 1.26-4.50, P = 0.008). Conclusion: High serum procalcitonin level is an independent prognostic biomarker of mortality risk in critically ill patients with ventilator-associated pneumonia, and it's a promising biomarker of prognosis in critically ill patients.


2021 ◽  
Author(s):  
Rehab Farouk Mohamed ◽  
Donia Hussein Abd El Hameed ◽  
Mohamed Alaa Eldeen Hassan

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.


2002 ◽  
Vol 20 (18) ◽  
pp. 3850-3856 ◽  
Author(s):  
Mauro Piantelli ◽  
Stefano Iacobelli ◽  
Giovanni Almadori ◽  
Manuela Iezzi ◽  
Nicola Tinari ◽  
...  

PURPOSE: Galectin-3 is a pleiotropic carbohydrate-binding protein participating in a variety of normal and pathologic processes, including cancer progression. This study was aimed at evaluating the prognostic value of galectin-3 expression in node-negative laryngeal squamous-cell carcinoma (SCC). PATIENTS AND METHODS: Galectin-3 expression was analyzed by immunohistochemistry using M3/38 monoclonal antibody, in a single-institution series of 73 node-negative laryngeal SCC patients (median follow-up, 52 months; range, 2 to 90 months). RESULTS: Forty-two (57.5%) of 73 patients expressed galectin-3. Galectin-3 expression was positively associated with tumor keratinization and histologic grade. A significant correlation was found between galectin-3 tumor positivity and longer relapse-free and overall survival. In univariate analysis, high-grade (grade 3 or 4) tumors, nonkeratinizing tumors, and galectin-3–negative tumors showed a significantly increased risk of relapse and death. In multivariate analysis, only galectin-3 expression retained an independent prognostic significance for both relapse-free and overall survival. CONCLUSION: We conclude that the absence of galectin-3 expression is an independent negative prognostic marker in laryngeal SCC patients. Thus, histochemical detection of galectin-3 in these tumors could be useful for the selection of node-negative patients with potentially unfavorable outcomes, to establish adjuvant therapy protocols.


1983 ◽  
Vol 69 (6) ◽  
pp. 527-530 ◽  
Author(s):  
Stefano Ciatto ◽  
Patrizia Bravetti ◽  
Gaetano Cardona ◽  
Luigi Cataliotti ◽  
Roberto Crescioli ◽  
...  

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N– cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N– cases should be reconsidered.


2019 ◽  
Vol 8 (9) ◽  
pp. 1358 ◽  
Author(s):  
Lee ◽  
Kim ◽  
Lee ◽  
Han ◽  
Lee ◽  
...  

This study aimed to evaluate the association between abdominal-to-gluteofemoral adipose tissue (AT) distribution and recurrence-free survival (RFS) in breast cancer patients. Staging F-18 fluorodexoyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of 336 women with breast cancer were retrospectively analyzed. From CT images, the volume and CT-attenuation of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), and gluteofemoral AT were measured and the ratio of abdomen-to-gluteofemoral AT volume (AG volume ratio) was calculated. The relationships between adipose tissue parameters and RFS were assessed. Through univariate analysis, abdominal SAT volume, gluteofemoral AT volume, and AG volume ratio were significantly associated with RFS. An increase in abdominal SAT volume and AG volume ratio were associated with an increased risk of recurrence, whereas increased gluteofemoral AT volume was associated with a decreased risk of recurrence. On multivariate analysis, abdominal SAT volume, gluteofemoral AT volume, and AG volume ratio were found to be significant predictors of RFS after adjusting for clinic-histological factors. Irrespective of obesity, patients with a high AG volume ratio showed a higher recurrence rate than those with a low AG volume ratio. Increased abdominal SAT volume and decreased gluteofemoral AT volume were related to poor RFS in breast cancer patients.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4088-4088
Author(s):  
Afsaneh Barzi ◽  
Takeru Wakatsuki ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
Fotios Loupakis ◽  
...  

4088 Background: LMTK3 is an estrogen receptor α (ERα) regulator. Recent studies show that [rs808419(r8) and rs9989661(r9)] and LMTK3 expression are prognostic in breast and colon cancers. Our group demonstrated that r9AA is associated with shorter time to recurrence in Caucasian(C) and Hispanic(H) females(F) with GAC. We investigated the significance of LMTK3 polymorphism in J PTS with GAC. Methods: Blood or tissue samples of 169 J PTS who had surgery with/without adjuvant chemotherapy (ACT) were analyzed. Genomic DNA was extracted using the QIAmp kit; all samples were analyzed using PCR-based direct DNA-sequencing. The endpoints of the study were disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were used for univariate analysis. Multivariate analysis was performed to test the interaction between polymorphism and gender adjusting for other variables. Results: 60 F and 109 males were enrolled in this study, 17% stage(s) IB, 31% s II, 36% s III, 17% s IV (AJCC-6). The median age was 67(31-88). 65% of PTS received S-1 based ACT. Median follow-up was 4 years(ys). Prognosis was worse in men with r9 AA than AG/GG, at 1 year 67% (95% CI 40-83%) with AA vs 99% (95% CI 91-99%) of AG/GG were alive (p= 0.039). Median survival was not reached in the AG/GG group; in the AA group median DFS and OS was 1yr (p= 0.03) and 2ys (p= 0.039) respectively. In the multivariate analysis adjusting for s, age, and ACT, males carrying AA had increased risk of disease recurrence (HR 3.84 95%CI 1.86-7.92, p< 0.001) and dying (HR 3.47 95%CI 1.58-7.62 p=0.002) compared to those with AG/GG (HR=1, reference). Conclusions: r9 AA was associated with significantly worse DFS and OS in J male with GAC. These results confirm our previous findings that LMTK3 is an independent prognostic factor for localized GAC; interestingly the relationship between gender and prognostic significance is the opposite in J vs. C/H. The gender disparity can be due to the differences in the etiology (histological subtypes), management strategies, allele frequency, and degree of estrogen exposure in the two populations. Additional studies are warranted to identify the underlying biological mechanism.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14595-e14595
Author(s):  
Manuel Valladares-Ayerbes ◽  
Nuria Tarrío ◽  
Moisés Blanco-Calvo ◽  
Mar Haz-Conde ◽  
Isabel Santamarina Cainzos ◽  
...  

e14595 Background: MIC1 and MMP7 are secreted cytokines involved respectively in the modulation of immunological processes and in extracellular matrix remodeling. Their expression were found deregulated in different tumors, including GC. However, few data are available about their serum levels, their diagnostic potential, and their prognostic significance in GC pts. Here, we analyze the diagnostic performance of these markers and we present data linking them with short survival in GC pts. Methods: Serum samples were assayed in duplicate for MIC1 and MMP7 levels by ELISA. The diagnostic performance of markers was assessed by ROC curve analysis and the cut-offs were set using the Youden index approach. The cut-offs for prognostic purposes were determined using X-tile software. Differences in progression free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and logrank test. Cox regression was used to determine the prognostic independence of biomarkers. Results: From November 2006 to July 2010, 52 GC pts and 28 healthy donors were consecutively recruited. The follow-up of pts was performed until their death or the end of study (September 2011). The AUCs for MIC1 and MMP7 were respectively 0.897 and 0.865 (p < 0.001). Using the optimal cut-off to diagnose GC pts, we obtained a 73.08% of sensitivity (Ss) and a 92.86% of specificity (Sp) for MIC1, and a 78.85% of Ss and an 85.71% of Sp for MMP7. In the survival analysis, high serum levels of MIC1 and MMP7 were significantly associated with shorter PFS (p < 0.001) and OS (p < 0.001 and p = 0.003, respectively). In univariate analysis, pts with high serum levels of MIC1 and MMP7 had an increased risk of progression (HR = 3.608, p<0.001 for MIC1; HR = 4.172, p<0.001 for MMP7) and death (HR = 3.843, p=0.001 for MIC1; HR = 2.602, p=0.006 for MMP7). However, MIC1 and MMP7 failed to reach prognostic independence in multivariate analysis. Conclusions: We obtained cut-off values of MIC1 and MMP7 in serum for diagnostic purposes in GC. In addition, we established a correlation between increased levels of MIC1 and MMP7 in serum and shorter PFS and OS in GC. These findings justify studies with a larger number of pts.


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