Prognostic impact of allelic losses in 1p32–36 (HYTM1), 4p15.2 (D4S2397), 5q22.2 (D5S346), 8p22 (D8S254), 18q12.3 (D18S474), and microsatellite instability for colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4132-4132
Author(s):  
R. Melcher ◽  
T. Kudlich ◽  
H. Luehrs ◽  
T. Katzenberger ◽  
B. Illert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Normal Mucosa ◽  
Stage I ◽  
Rank Test ◽  
Allelic Loss ◽  
Prognostic Impact ◽  
Tumour Stage

4132 Background: The aim of this prospective study was to analyse the prognostic impact of allelic losses in the chromosomal regions 1p32–36 (HYTM1), 4p14–16 (D4S2397), 5q22 (D5S346), 8p21–22 (D8S254), 18q12.3 (D18S474) and microsatellite instability (MSI) in colorectal cancer (CRC). The microsatellite markers HYTM1, D4S2397, D8S254, and D18S474 were previously shown to have prognostic relevance in retrospective studies. The National Cancer Institute (NCI) microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI-Analysis. Methods: Between July 1999 and February 2004, the data from a total of 165 patients, preoperatively diagnosed with colorectal cancer, and operated on in the Department of Surgery, University of Wuerzburg were collected. Inclusion criteria were: (a) electively operated primary adenocarcinomas; (b) obtainment of fresh paired normal mucosa-tumor samples; (c) no postoperative death (survival < 1 month); and (d) availability of follow-up data. Allelic loss (LOH) was determined by comparing the PCR-patterns of tumor DNA with corresponding normal tissue (signal reduction of at least 50%). MSI-L (low microsatellite instability) was defined as one marker out of five NCI-markers, MSI-H (high microsatellite instability) as more than two markers to display microsatellite instability. MSI-H tumours were excluded for further LOH-analysis. The endpoint of the study was tumour specific death. Kaplan-Meier survival curves were compared using the log-rank test. Results: We found expected frequencies in age, gender, tumour stage, and tumour grading. Tumour stage, grading, and an allelic loss of D18S474 was confirmed to be of prognostic significance for UICC I-IV, I-III, and II cancer in univariate analysis. Tumour stage and LOH D18S474 were also independent prognostic variables in stage I-IV and I-III. There was no significant prognostic impact of a loss of the markers HYTM1, D4S2397, D5S346, D8S254, MSI-L and MSI-H in either UICC stage I-IV, I-III, and II colorectal cancer patients. Conclusions: A loss of D18S474 defines a high-risk subgroup of patients with stage I-IV, I-III and stage II colorectal cancers. No significant financial relationships to disclose.

scholarly journals Downregulation of PAICS due to loss of chromosome 4q is associated with poor survival in stage III colorectal cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247169
Author(s):  
Yusuke Kobayashi ◽  
Kensuke Kumamoto ◽  
Hirokazu Okayama ◽  
Takuro Matsumoto ◽  
Hiroshi Nakano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Progression ◽  
De Novo ◽  
Prognostic Significance ◽  
Normal Mucosa ◽  
Stage Iii ◽  
Copy Number Loss ◽  
Prognostic Impact ◽  
Cancer Specific Survival ◽  
Adjacent Mucosa

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) encodes an enzyme that catalyzes de novo purine biosynthesis. Although PAICS has been implicated as a potential therapeutic target in several cancers, its clinical and prognostic significance in colorectal cancer (CRC) is not fully understood. To elucidate the roles of PAICS in CRC, we investigated PAICS expression in four cohorts consisting of a total of 1659 samples based on quantitative RT-PCR, microarray and RNA-seq analysis. Despite upregulated PAICS levels in tumor compared to those of normal mucosa, we found a decreasing trend of PAICS expression during tumor progression and metastasis. We conducted immunohistochemistry on 252 specimens, showing that PAICS protein was strongly expressed in the majority of CRCs, but not in adjacent mucosa. Notably, 29.0% of tumors lacked PAICS staining, and PAICS-negative expression in tumor had significant prognostic impact on poor cancer-specific survival in stage III CRC. Correspondingly, decreased levels of PAICS transcript were also correlated with poor relapse-free survival particularly in stage III patients, and this finding was robustly confirmed in three microarray datasets of a total of 802 stage II-III patients. Bioinformatics analysis of CRC tissues and cell lines consistently indicated a correlation between decreased PAICS expression and copy number loss of chromosome arm 4q. In conclusion, our results suggest that PAICS expression is downregulated during tumor progression due to genetic deletion of chromosome 4q in microsatellite stable but chromosomally unstable tumors. Furthermore, decreased expression of PAICS transcript or loss of PAICS protein may provide prognostic stratification for postoperative patients with stage III CRC.

Adverse Prognostic Effect of Methylation in Colorectal Cancer Is Reversed by Microsatellite Instability

2003 ◽  
Vol 21 (20) ◽  
pp. 3729-3736 ◽  
Author(s):  
Robyn Lynne Ward ◽  
Kay Cheong ◽  
Su-Lyn Ku ◽  
Alan Meagher ◽  
Terence O’Connor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Microsatellite Instability ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Curative Surgery ◽  
Fresh Tissue ◽  
Vascular Space ◽  
Response To Chemotherapy ◽  
Vascular Space Invasion

Purpose: DNA methylation is an important biologic event in colorectal cancer and in some cases is associated with the development of microsatellite instability (MSI). In this study, we sought to determine the prognostic significance of DNA methylation, both in univariate analysis and in concert with other clinicopathologic factors known to influence outcome. Patients and Methods: Fresh tissue (625 cancers) was obtained from 605 individuals (age range, 29 to 99 years) undergoing curative surgery for colorectal cancer at one institution during a period of 8 years. Clinicopathologic details were recorded for all tumors, including stage, grade, type, vascular space invasion, and clinical follow-up to 5 years. Microsatellite status was assessed using standard markers. Methylation of p16 and hMLH1 promoters was determined by methylation-specific polymerase chain reaction (PCR), whereas methylation at methylated-in-tumor loci (MINT)1, MINT2, MINT12, and MINT31 loci were assessed by bisulfite-PCR. Results: Patients with microsatellite unstable tumors (12%) had better disease-specific survival than those with microsatellite stable (MSS) tumors (univariate analysis: hazard ratio [HR], 0.53; 95% CI, 0.27 to 1.0). Overall survival of individuals with MSS tumors was influenced by three independently significant factors: tumor stage (HR, 7.3; 95% CI, 5.1 to 10.4), heavy tumor methylation (HR, 2.1; 95% CI, 1.1 to 4.0), and vascular space invasion (HR, 1.9; 95% CI, 1.3 to 2.9). In MSS tumors, methylation at any single site was not independently predictive of survival. Neither methylation nor microsatellite status predicted a favorable response to chemotherapy. Conclusion: DNA methylation is associated with a worse outcome in colorectal cancer, but this adverse prognostic influence is lost in those methylated tumors showing MSI. The mechanisms of these events warrant additional investigation.

Risk factors predicting colorectal cancer recurrence in a Latin American population.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15180-e15180
Author(s):  
Jorge Leon ◽  
Fernando Namuche ◽  
Paola Catherine Montenegro ◽  
Claudio J. Flores
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Latin American ◽  
Tumor Size ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Lymph Node Involvement ◽  
Stage I ◽  
Rank Test ◽  
Node Involvement

e15180 Background: The incidence of colorectal cancer (CRC) in Peru has increased in the last decades. In our population more than 80% of patients are stage I-III. Recurrence is one of the most important factors to consider in the survival of CRC patients. The aim of this study was to identify which factors influence in the recurrence of CRC in our population. Methods: We retrospectively reviewed the electronic medical records of 506 patients with stage I-III CRC from one specialized Peruvian cancer center between 2006 and 2016. Survival analysis (with recurrence as the event to evaluate) was performed with Kaplan Meier curves and Long-rank test. We use a preliminary univariate analysis to do the multivariate analysis with Cox regression. We performed a ROC curve analysis to determine an appropriate cut-off value for the tumor size (≥4.2). Results: In the univariate analysis we found that sidedness, tumor size (cut-off ≥4.2), CEA, lymph node involvement, stage, histological grade, LVI, PNI, and chemotherapy were statistically significant. In the multivariate model, tumor size [HR, 1.462; 95% CI, 1.065-2.217; p<0.05], lymph node involvement [HR, 0.136; 95% CI,0.41-0.447; p<0.001], and stage III [HR, 0.003; 95% CI, 0.263-0.758; p<0.05] retained a significant association and were independent factors with relapse disease. Conclusions: In stage I-III CRC pts it is important to evaluate tumor size, lymph node involvement and clinical stage as they are possible prognostic factors that will help our diagnosis and treatment along with other standard features.

scholarly journals An Applicable Inflammation-Joined and Nutrition-Related Prognostic Indicator in Patients With Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guo Wu ◽  
Jungang Liu ◽  
Haizhou Liu ◽  
Lan Jin ◽  
Xiaoliang Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Protective Factor ◽  
Multivariate Analyses ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Tnm Stage ◽  
Rank Test ◽  
Node Positive ◽  
Lymph Node Positive

PurposeThis study aimed to elucidate the prognostic significance of a novel inflammation-joined and nutrition-related clinicopathological marker for colorectal cancer (CRC).MethodsVarious factors from preoperative fasting blood samples from 2471 patients with CRC were retrospectively analyzed. Factors related to prognosis were evaluated using univariate and multivariate analyses. The Kaplan–Meier method was used to generate survival curves, while the log-rank test was used to measure survival differences between groups.ResultsUnivariate analysis revealed that C-reactive protein (CRP)/mean corpuscular volume (MCV) ratio, TNM stage, differentiation, right-sided tumor, age, carcinoembryonic antigen (CEA) level, and CRP level were significantly associated with poor prognosis in CRC. In contrast, adjuvant chemotherapy is regarded as a protective factor. Elevation of CRP/MCV ratio (odds ratio [OR]: 1.535, 95% confidence interval [CI]: 1.121–2.104, P = 0.008), TNM stage (OR: 2.747, 95% CI: 2.175–3.469, P &lt; 0.001), and differentiation (OR, 1.384; 95% CI, 1.150–1.666; P = 0.001) were prognostic risk factors in the multivariate analyses. Subgroup analysis showed that CRP/MCV, TNM staging system, and differentiation also independently affected survival in patients with lymph node-positive CRC. The nomogram based on these three indicators showed that CRP/MCV had a greater prognostic value and clinical significance for lymph node-positive patients with poorly differentiated tumors at the late stage.ConclusionA novel nomogram using the clinicopathologic index of inflammation and nutrition was constructed to predict the prognosis of CRC. Early interventions should be emphasized for advanced-stage patients with severe inflammation and poor nutritional status.

scholarly journals Prognostic significance of bone marrow and spleen 18F-FDG uptake in patients with colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae-Hoon Lee ◽  
Hye Sun Lee ◽  
Soyoung Kim ◽  
Eun Jung Park ◽  
Seung Hyuk Baik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bone Marrow ◽  
Inflammatory Markers ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Uptake Ratio ◽  
Liver Uptake ◽  
Fdg Uptake ◽  
Standardized Uptake Values ◽  
Serum Inflammatory Markers

AbstractSerum inflammatory markers are used in the prognostication of colorectal cancer (CRC); however, the corresponding role of positron emission tomography (PET)-derived inflammatory markers remains unclear. This study aimed to investigate the prognostic value of 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow and spleen of patients with CRC and evaluate the relationship between FDG uptake estimates in these organs and serum inflammatory markers. In total, 411 patients who underwent preoperative FDG PET/computed tomography (CT) within 1 month of surgery were enrolled. The mean standardized uptake values of the bone marrow and spleen were normalized to the value of the liver, thereby generating bone marrow-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) estimates. The value of BLR and SLR in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between BLR or SLR and neutrophil-to-lymphocyte ratio (NLR) was evaluated. The predictive accuracy of BLR alone and in combination with SLR was compared using the integrated area under the receiver operating characteristic curves (iAUC). In the univariate analysis, BLR (> 1.06) and SLR (> 0.93) were significant predictors of OS. In the multivariate analysis, BLR was an independent predictor of OS (hazard ratio = 5.279; p < 0.001). Both BLR and SLR were correlated with NLR (p < 0.001). A combination of BLR and SLR was better than BLR alone at CRC prognostication (iAUC, 0.561 vs. 0.542). FDG uptake estimates in the bone marrow and spleen may be useful imaging-derived biomarkers of systemic inflammation, supporting CRC prognostication.

Prognostic Impact of Hypochloremia in Patients With Stage I to III Colorectal Cancer After Radical Resection

2018 ◽  
Vol 61 (11) ◽  
pp. 1273-1280
Author(s):  
Qingguo Li ◽  
Weixing Dai ◽  
Huixun Jia ◽  
Yaqi Li ◽  
Ye Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radical Resection ◽  
Stage I ◽  
Prognostic Impact

Impact of BRAF mutations on prognosis and immunotherapy response in microsatellite instability/mismatch repair deficient metastatic colorectal cancer: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3557-3557
Author(s):  
Robin Park ◽  
Laércio Lopes da Silva ◽  
Sunggon Lee ◽  
Anwaar Saeed
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Braf Mutation ◽  
Meta Analysis ◽  
Stage Iv ◽  
Stage I ◽  
Prognostic Impact ◽  
Braf Mutations ◽  
Mutation Status ◽  
The Impact

3557 Background: Mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC) defines a molecular subtype with distinct clinicopathologic characteristics including an excellent response to immunotherapy. Although BRAF mutations are established as a negative prognostic marker in CRC, whether they retain their negative prognostic impact in or alter the response to immunotherapy in dMMR/MSI-H CRC remains unknown. Herein, we present a systematic review and meta-analysis of the impact of BRAF mutations on the overall survival (OS) and immune checkpoint inhibitor (ICI) response in dMMR/MSI-H CRC. Methods: Studies published from inception to 26 January 2021 were searched in PubMed, Embase, and major conference proceedings (AACR, ASCO, and ESMO). Eligible studies included the following: 1) observational studies reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients and 2) experimental studies of ICI reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients. A summary hazard ratio (HR) was calculated for OS in BRAF mutated ( BRAFmut) vs. BRAF wild type ( BRAFwt) patients (pts) with the random effects meta-analysis (REM). A summary odds ratio (OR) was calculated for objective response rate (ORR) in BRAFmut vs. BRAFwt pts treated with ICI with the REM. Results: Database search conducted according to PRISMA guidelines found 4221 studies in total. Initial screening identified 30 studies and after full-text review, 9 studies (N = 4158 pts) were included for the meta-analysis of prognosis (analysis A) and 3 studies (N = 178 pts) were included for the meta-analysis of ICI response (analysis B). The outcome measures are summarized in the table below. Analysis A showed that in stage I-IV dMMR/MSI-H CRC pts, BRAFmut was associated with worse OS than BRAFwt (HR 1.57, 1.23-1.99). The heterogeneity was low (I2 = 21%). Subgroup analysis showed no significant difference in the prognostic impact of BRAF mutation status between stage IV only and stage I-IV CRC pts. Analysis B showed no difference in ORR (OR 1.04, 0.48-2.25) between BRAFmut vs. BRAFwt dMMR/MSI-H pts who received ICI. The heterogeneity was low (I2 = 0%). Conclusions: BRAF mutations retain their negative prognostic impact in dMMR/MSI-H stage I-IV and stage IV CRC but are not associated with differential ICI response. Limitations include the following: analysis A was based on retrospective studies; also, the impact of BRAF status on the survival outcome of ICI could not be assessed due to limited number of studies.[Table: see text]

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

Non-ocular melanomas in cats: a retrospective study of 30 cases

2016 ◽  
Vol 19 (4) ◽  
pp. 351-357 ◽  
Author(s):  
Gabriel Chamel ◽  
Jérôme Abadie ◽  
Olivier Albaric ◽  
Sophie Labrut ◽  
Frédérique Ponce ◽  
...  
Keyword(s):  
Mitotic Index ◽  
Primary Tumour ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinical Signs ◽  
Surgical Margins ◽  
Rank Test ◽  
Kaplan Meier ◽  
Product Limit ◽  
Junctional Activity

Objectives The aim of the study was to describe the clinical outcome of 30 cats with non-ocular melanomas and to evaluate the association between clinical or pathological parameters and overall survival time. Methods The database of the animal histopathological laboratory of the National Veterinary School of Nantes (Oniris, Nantes, France) was retrospectively searched to identify cases of feline non-ocular melanomas between December 2009 and April 2014. For each case, clinical data, including signalment, location of the primary tumour, staging, treatment and outcome, were collected from the medical records or via interviews with referring veterinarians. Histological and immunohistochemical evaluation included mitotic index, cytonuclear atypias, junctional activity, Melan A and S100 immunostaining, and surgical margins. Univariate analysis to test the prognostic value of the different variables was performed by the Kaplan–Meier product limit method using the log-rank test of significance. Results Thirty cats were included in the study. Eleven had a cutaneous non-auricular melanoma, six had a tumour located on the pinna and 13 had a tumour in the oral cavity. Cats with auricular melanomas were significantly younger than cats with tumours in other locations. Location and presence of clinical signs were not of prognostic significance, but the achromic phenotype was significantly associated with a poorer prognosis. Twenty cats were treated with surgery and survived significantly longer than cats that received only medical treatment or that did not receive any treatment. According to our data, mitotic index, cytonuclear atypias, junctional activity, Melan A or S100 expression, and surgical margins were not associated with survival. Conclusions and relevance We show for the first time, in a large series, that the auricular form of melanoma affected significantly younger cats than other extraocular forms. Most feline non-ocular melanomas are malignant and achromic tumours are associated with a poorer prognosis. According to this study, surgery should be considered as a priority.

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