scholarly journals Expression of ERα, ERβ and Co-Regulator PELP1/MNAR in Colorectal Cancer: Prognostic Significance and Clinicopathologic Correlations

2009 ◽  
Vol 31 (3) ◽  
pp. 235-247
Author(s):  
Petros D. Grivas ◽  
Vassiliki Tzelepi ◽  
Georgia Sotiropoulou-Bonikou ◽  
Zinovia Kefalopoulou ◽  
Athanasios G. Papavassiliou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Cells ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Normal Mucosa ◽  
Colorectal Carcinogenesis ◽  
Colorectal Tumorigenesis ◽  
Free Survival ◽  
Colorectal Tissue ◽  
Favorable Prognostic Factor

Background: Estrogen receptor β (ERβ) is abundantly expressed in colorectal tissue, but its role in colorectal carcinogenesis remains elusive. ER novel co-regulator, proline-, glutamic acid- and leucine-rich protein 1 (PELP1/MNAR) has been characterized, but its expression in colorectal carcinomas has not been investigated.Methods: ERα, ERβ and PELP1/MNAR protein expression were evaluated by immunohistochemistry in colorectal normal mucosa, adenomas and adenocarcinomas from 113 patients with colorectal cancer.Results: ERα expression is extremely rare in colorectal tissue and its expression does not appear to be associated with colorectal carcinogenesis. ERβ and PELP1/MNAR were detected in the nucleus of epithelial, endothelial, inflammatory, smooth muscle cells and myofibroblasts. When intensity of staining was taken into account, the expression of both proteins was significantly increased in epithelial cells of carcinomas compared to normal mucosa. ERβ expression in epithelial cells was correlated with decreased disease progression – free survival. PELP1/MNAR overexpression in epithelial cells was found to be an independent favorable prognostic factor. Additionally, the expression of both proteins was significantly increased in stromal myofibroblasts of carcinomas compared to adenomas and normal mucosa.Conclusion: ERβ and PELP1/MNAR appear to be involved in colorectal tumorigenesis and might have prognostic significance.

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

scholarly journals Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study

2019 ◽  
Vol 13 ◽  
pp. 117955491882544 ◽  
Author(s):  
Ali Aljubran ◽  
Mahmoud A Elshenawy ◽  
Magdy Kandil ◽  
Muhammed N Zahir ◽  
Ahmed Shaheen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Free Survival

Background: Regorafenib is a multi-kinase inhibitor approved for treatment of refractory advanced colorectal cancer. It was found in the clinical trials to have a modest benefit and significant toxicity. Our aim was to assess the outcome in our local clinic practice. Patients and methods: Records of patients with confirmed colorectal cancer treated with regorafenib were reviewed. Clinical, pathological, and molecular data were collected. Efficacy and factors of possible prognostic significance were analyzed. Results: A total of 78 patients with metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016 in 4 different institutions (median age: 50.5 years; male: 40 [51.3%]; KRAS mutant: 41 [52%]; right colonic primary: 18 [23%]). A total of 52 patients (66.7%) had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, whereas in 25 patients (32.1%) it was >1. In total, 58 patients (74%) had dose reduction. No patient achieved objective response, 15 patients (19%) achieved stable disease, and 56 patients (72%) had progressive disease. With a median follow-up of 6.5 months, the median progression-free survival was 2.8 months (95% confidence interval [CI], 2.5-3.3) and overall survival was 8.0 months (95% CI, 6.2-9.7). Only performance status of ⩽1 had a statistically significant impact on progression-free survival and overall survival in both univariate and multivariate analyses. Conclusions: Regorafenib in our clinical practice has equal efficacy to reported data from pivotal registration trials. Our data suggest that performance status is the most important prognostic factor in patients treated with regorafenib, suggesting a careful selection of patients.

scholarly journals Neonatal Nav1.5 Protein Expression in Human Colorectal Cancer: Immunohistochemical Characterization and Clinical Evaluation

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3832
Author(s):  
Elena Lastraioli ◽  
Scott P. Fraser ◽  
R. Mine Guzel ◽  
Jessica Iorio ◽  
Lapo Bencini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Expression Patterns ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Normal Mucosa ◽  
Free Survival ◽  
Human Carcinomas ◽  
Clinical Biomarker ◽  
High Level

Voltage-gated Na+ channels (VGSCs) are expressed widely in human carcinomas and play a significant role in promoting cellular invasiveness and metastasis. However, human tissue-based studies and clinical characterization are lacking. In several carcinomas, including colorectal cancer (CRCa), the predominant VGSC is the neonatal splice variant of Nav1.5 (nNav1.5). The present study was designed to determine the expression patterns and clinical relevance of nNav1.5 protein in human CRCa tissues from patients with available clinicopathological history. The immunohistochemistry was made possible by the use of a polyclonal antibody (NESOpAb) specific for nNav1.5. The analysis showed that, compared with normal mucosa, nNav1.5 expression occurred in CRCa samples (i) at levels that were significantly higher and (ii) with a pattern that was more delineated (i.e., apical/basal or mixed). A surprisingly high level of nNav1.5 protein expression also occurred in adenomas, but this was mainly intracellular and diffuse. nNav1.5 showed a statistically significant association with TNM stage, highest expression being associated with TNM IV and metastatic status. Interestingly, nNav1.5 expression co-occurred with other biomarkers associated with metastasis, including hERG1, KCa3.1, VEGF-A, Glut1, and EGFR. Finally, univariate analysis showed that nNav1.5 expression had an impact on progression-free survival. We conclude (i) that nNav1.5 could represent a novel clinical biomarker (‘companion diagnostic’) useful to better stratify CRCa patients and (ii) that since nNav1.5 expression is functional, it could form the basis of anti-metastatic therapies including in combination with standard treatments.

Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Systematic Review and Meta-Analysis

2004 ◽  
Vol 22 (3) ◽  
pp. 529-536 ◽  
Author(s):  
Sanjay Popat ◽  
Athena Matakidou ◽  
Richard S. Houlston
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Thymidylate Synthase ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Small Sample ◽  
Sample Sizes ◽  
Free Survival ◽  
Small Sample Sizes

Purpose A number of studies have investigated the relationship between thymidylate synthase (TS) expression and survival in colorectal cancer (CRC) patients. Although most have reported poorer overall and progression-free survival with high TS expression, estimates of the hazard ratio (HR) between studies differ wildly. To derive a more precise estimate of the prognostic significance of TS expression, we have reviewed published studies and carried out a meta-analysis. Materials and Methods Twenty studies stratifying overall survival and/or progression-free survival in CRC patients by TS expression status were eligible for analysis. The principal outcome measure was the HR. Data from these studies were pooled using standard meta-analysis techniques. Results Thirteen studies investigated outcome in a total of 887 cases with advanced CRC, and seven studies investigated outcome in a total of 2,610 patients with localized CRC. A number of methods were used both to assess TS expression and to assign TS status. Sample sizes varied greatly, small sample sizes being a feature of the advanced disease studies. The combined HR estimate for overall survival (OS) was 1.74 (95% CI, 1.34 to 2.26) and 1.35 (95% CI, 1.07 to 1.80) in the advanced and adjuvant settings, respectively, but there was evidence of heterogeneity and possible publication bias. Conclusion Tumors expressing high levels of TS appeared to have a poorer OS compared with tumors expressing low levels. Additional studies with consistent methodology are needed to define the precise prognostic value of TS.

scholarly journals Clinicopathological and prognostic significance of PD-L1 expression in colorectal cancer: a meta-analysis

2020 ◽  
Vol 36 (1) ◽  
pp. 117-130
Author(s):  
Shuxia Wang ◽  
Bo Yuan ◽  
Yun Wang ◽  
Mingyang Li ◽  
Xibo Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Clinicopathological Features ◽  
Cochrane Library ◽  
Free Survival ◽  
Meta Regression ◽  
Disease Free

Abstract Purpose To systematically evaluate the correlation between PD-L1 expression and clinicopathological features and prognosis of colorectal cancer (CRC). Methods Seven databases (PubMed, Cochrane Library, EMBASE, Web of Science, CBM, Wanfang, and CNKI) were searched through May 2020. Risk of bias and quality of evidence were assessed by using the Newcastle–Ottawa scale (NOS), and meta-analysis was carried out by using the Review Manager 5.3 software on the studies with the quality evaluation scores ≥ 6. Meta-regression analysis was used to determine the independent role of PD-L1 expression on CRC prognosis after adjusting clinicopathological features and treatment methods. Results A total of 8823 CRC patients in 32 eligible studies. PD-L1 expression was correlated with lymphatic metastasis (yes/no; OR = 1.24, 95% CI (1.11, 1.38)), diameter of tumor (≥ 5 cm/< 5 cm; OR = 1.34, 95% CI (1.06, 1.70)), differentiation (high–middle/low; OR = 0.68, 95% CI (0.53, 0.87)), and vascular invasion (yes/no; OR = 0.80, 95% CI (0.69, 0.92)). PD-L1 expression shortened the overall survival (hazard ratio (HR) = 1.93, 95% CI (1.66, 2.25)), disease-free survival (HR = 1.76, 95% CI (1.50, 2.07)), and progression-free survival (HR = 1.93, 95% CI (1.55, 2.41)). Meta-regression showed that PD-L1 expression played a significant role on poor CRC OS (HR = 1.95, 95% CI (1.92, 3.98)) and disease-free survival (HR = 2.14, 95% CI (0.73, 4.52)). Conclusion PD-L1 expression independently predicted a poor prognosis of CRC.

Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in right-sided and left-sided colon cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 182-182
Author(s):  
Ben McCormick ◽  
Pranitha Prodduturvar ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Leander Grimm ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Normal Mucosa ◽  
Free Survival ◽  
Adjacent Normal Mucosa ◽  
The Mean ◽  
Cd63 Expression

182 Background: Exosomes play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. Their pattern of expression and prognostic significance in patients with RSCC and LSCC is unknown. This study explored CD63 and CD9 expression and prognostic significance in patients with RSCC and LSCC using immunohistochemistry (IHC). Methods: Between 2015 and 2018, 63 patients underwent surgical resection of colon cancer for whom we had available tissues for CD63 and CD9 IHC staining. Two pathologists independently scored the CD63 and CD9 expression in the tumor and adjacent normal mucosa (ANM). Staining intensity was graded 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (intensity X percentage of staining) was calculated. Results: RSCC and LSCC represented 52% and 48% of the patients respectively. The ANM and Tumor CD63 Q-scores were 225 vs 191 (p = 0.009) in RSCC and 224 vs 154 (p = 0.0001) in LSCC, respectively. The ANM and Tumor CD9 Q-scores were 134 vs 152 (p = 0.142) in RSCC and 135 vs 154 (p = 0.137) in LSCC, respectively. In patients with RSCC and LSCC, the mean Tumor CD63 Q-score was 191 vs 154 (p = 0.024), while the mean ANM CD63 Q-score was 225 vs 224 (p = 0.920). The mean Tumor CD9 Q-score was 152 and 154 (p = 0.883), and the mean ANM CD9 Q-score was 134 vs 135 (p = 0.926). In our cohort, there was no difference in progression free survival (PFS) between patients with RSCC and LSCC (p = 0.2349). In all patients, there was no difference in PFS in patients with CD63 expression < 100 and ≥100 (p = 0.8284). Among patients with RSCC, there was a significantly lower PFS in patients with CD63 expression < 100 vs. ≥100 (p = 0.0259). However, among patients with LSCC, there was no difference in PFS in patients with CD63 expression < 100 vs. ≥100 (p = 0.3494). Conclusions: To our knowledge, this is the first study to show a difference in exosomal marker (CD63) expression pattern and its prognostic significance in patients with RSCC and LSCC. There was a significant positive correlation between progression free survival in patients with RSCC and higher exosomal expression.

scholarly journals The Prognostic Significance of Combined Pretreatment Fibrinogen and Neutrophil-Lymphocyte Ratio in Various Cancers: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Rongqiang Liu ◽  
Shiyang Zheng ◽  
Qing Yuan ◽  
Peiwen Zhu ◽  
Biao Li ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Regression Analyses ◽  
Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Meta Regression

Purpose. The prognostic value of a new scoring system, termed F-NLR, that combines pretreatment fibrinogen level with neutrophil-lymphocyte ratio has been evaluated in various cancers. However, the results are controversial. The purpose of this study was to comprehensively analyze the prognostic value of F-NLR score in patients with cancers. Methods. An integrated search of relevant studies was conducted by screening the PubMed and Embase databases. Pooled hazard ratios, with 95% confidence intervals (CIs), for overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were calculated to estimate the prognostic significance of F-NLR score in patients with various tumors. A random effects model was used for comprehensive analysis, and subgroup and meta-regression analyses were used to explore sources of heterogeneity. Results. Thirteen articles reporting data from of 4747 patients were included in the study. Pooled analysis revealed that high F-NLR score was significantly associated with poor OS ( HR = 1.77 ; 95% CI, 1.51–2.08) and poor DFS/PFS ( HR = 1.63 ; 95% CI, 1.30–2.05). Subgroup and meta-regression analyses did not alter the prognostic role of F-NLR score in OS and DFS/PFS. Conclusions. Increased F-NLR score is significantly associated with poor prognosis in patients with cancers and can serve as an effective prognostic indicator.

scholarly journals Bevacizumab plus capecitabine as later-line treatment for patients with metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeong Hak Bang ◽  
Jeong Eun Kim ◽  
Ji Sung Lee ◽  
Sun Young Kim ◽  
Kyu-Pyo Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Median Overall Survival ◽  
Treatment Options ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Free Survival ◽  
Medical Need ◽  
Significant Disease

AbstractThere is an unmet medical need for later-line treatment options for patients with metastatic colorectal cancer (mCRC). Considering that, beyond progression, co-treatment with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate, we aimed to evaluate the efficacy of capecitabine and bevacizumab. This single-center retrospective study included 157 patients between May 2011 and February 2018, who received bevacizumab plus capecitabine as later-line chemotherapy after progressing with irinotecan, oxaliplatin, and fluoropyrimidines. The study treatment consisted of bevacizumab 7.5 mg/kg on day 1 and capecitabine 1,250 mg/m2 orally (PO) twice daily on day 1 to 14, repeated every 3 weeks. The primary endpoint was progression-free survival (PFS). The median PFS was 4.6 months (95% confidence interval [CI] 3.9–5.3). The median overall survival (OS) was 9.7 months (95% CI 8.3–11.1). The overall response rate was 14% (22/157). Patients who had not received prior targeted agents showed better survival outcomes in the multivariable analysis of OS (hazard ratio [HR] = 0.59, 95% CI 0.43–0.82, P = 0.002) and PFS (HR = 0.61, 95% CI 0.43–0.85, P = 0.004). Bevacizumab plus capecitabine could be a considerably efficacious option for patients with mCRC refractory to prior standard treatments.

scholarly journals Transarterial Radioembolization of Hepatocellular Carcinoma, Liver-Dominant Hepatic Colorectal Cancer Metastases, and Cholangiocarcinoma Using Yttrium90 Microspheres: Eight-Year Single-Center Real-Life Experience

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Julie Pellegrinelli ◽  
Olivier Chevallier ◽  
Sylvain Manfredi ◽  
Inna Dygai-Cochet ◽  
Claire Tabouret-Viaud ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Progression Free Survival ◽  
Single Center ◽  
Free Survival ◽  
Risk Of Death ◽  
Transarterial Radioembolization ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

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