Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status

2012 ◽  
Vol 65 (11) ◽  
pp. 996-1002 ◽  
Author(s):  
Viktor Hendrik Koelzer ◽  
Kristi Baker ◽  
Daniela Kassahn ◽  
Daniel Baumhoer ◽  
Inti Zlobec
Keyword(s):  
Protein Expression ◽  
Mismatch Repair ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Clinicopathological Features ◽  
Prognostic Impact ◽  
Mismatch Repair Status ◽  
First Time ◽  
Intra Class Correlation Coefficient

Backgroundβ-2-microglobulin (B2M) is essential for antigen presentation, yet may also possess proto-oncogenic properties.AimTo determine the prognostic impact of B2M in patients with mismatch repair (MMR) proficient and deficient colorectal cancer (CRC) and to investigate whether this effect on outcome is dependent on the local immune response. MethodsB2M protein expression and tumour-infiltrating immune cells (CD3, CD16, CD163, CD20, CD4, CD45RO, CD56, CD68, CD8, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1, TIA-1) were evaluated in a well characterised tissue microarray of 408 CRCs. The predictive value for clinicopathological features and the prognostic significance of B2M expression were analysed, stratified by MMR status and the immunohistological characteristics of immune cell infiltrates. ResultsInterobserver agreement for B2M staining was high (intra-class correlation coefficient=0.91). Complete B2M loss was more frequent in MMR-deficient (19.4%) compared to MMR-proficient (7.1%) tumours (p<0.001). In MMR-deficient cases, B2M loss predicted rare local recurrence (p=0.034), infrequent nodal-positivity (p=0.035), absence of distant metastasis (p=0.048; sensitivity=100%) and a trend towards favourable survival (p=0.124) independent of immune infiltrates. No associations between B2M and clinicopathological features were observed in MMR-proficient cases.ConclusionsOur data show for the first time that absence of B2M protein expression identifies MMR-deficient cancers with a favourable clinical course and absence of metastatic disease. Validation of B2M protein expression for sub-classification of MMR-deficient CRC is recommended for future clinical trials.

scholarly journals Reclassification of Kidney Clear Cell Carcinoma Based on Immune Cell Gene-Related DNA CpG Pairs

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 215
Author(s):  
Qizhan Luo ◽  
Thomas-Alexander Vögeli
Keyword(s):  
Cell Carcinoma ◽  
Immune Cell ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Pairwise Comparison ◽  
Clinicopathological Features ◽  
Immune Checkpoints ◽  
Potential Mechanism ◽  
Tissue Samples

Background: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs. Methods: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set. Results: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set. Conclusions: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.

scholarly journals Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
Jeng-Fu You ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Mismatch Repair ◽  
Multivariate Analyses ◽  
Extent Of Resection ◽  
Significant Difference ◽  
Tailored Approach ◽  
Mismatch Repair Status ◽  
Colorectal Cancer Patients

Abstract Background Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients. Patients and methods Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses. Results Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257–0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172–.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219–1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346–9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788–7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found. Conclusions Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.

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.

scholarly journals Cyclin D1 differential activation and its prognostic impact in patients with advanced breast cancer treated with trastuzumab

ESMO Open ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. e000441 ◽  
Author(s):  
G Mountzios ◽  
Vassiliki Kotoula ◽  
Georgia-Angeliki Kolliou ◽  
Kyriaki Papadopoulou ◽  
Georgios Lazaridis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Advanced Breast Cancer ◽  
Cyclin D1 ◽  
Prognostic Significance ◽  
D1 Protein ◽  
Advanced Breast ◽  
Prognostic Impact ◽  
Her2 Positive ◽  
Risk Of Progression

IntroductionWe sought to determine the level of activation of the critical components of the cyclin D1-mediated pathway and to evaluate their prognostic significance across the different molecular subtypes of advanced breast cancer.Patients and methodsThe study population comprised 219 female patients with advanced breast cancer who had been found to have human epidermal growth factor receptor 2 (HER2)-positive disease by local testing and were all treated with trastuzumab-based regimens. For all tumours, central testing for HER2 was performed, and cyclin D1 gene (CCND1) amplification, mRNA and protein expression were assessed by FISH, quantitative real-time-PCR and immunohistochemistry, respectively. Prognostic impact on clinical endpoints was evaluated with Cox regression analyses.ResultsAfter central testing, only 134 (61.2%) of 219 patients were confirmed to have HER2 gene amplification by FISH and/or 3+ HER2 protein expression by immunohistochemistry. After a median follow-up time of 136.0 months (95% CI 123.3 to 148.9), 105 (78.4%) HER2-positive patients and 76 (89.4%) HER2-negative patients had died, while 80% of the former and 87.1% of the latter had experienced a disease relapse. Patients with positive oestrogen receptor/progesterone receptor status presented with higher cyclin D1 mRNA expression. In the HER2-negative subgroup, patients with negative cyclin D1 protein expression were at higher risk of progression (HR= 1.66, 95%CI 1.01 to 2.72, Wald’s p=0.045). Among de novo metastatic patients, the risk of progression was higher for patients with non-amplified CCND1 tumours (HR= 2.00, 95% CI 1.03 to 3.90, p=0.041).ConclusionAberrant activation of the cyclin D1-mediated pathway appears to reduce the risk of progression in HER2-negative tumours, but not in HER2-positive ones.

Coexpression of MYC and BCL-2 Predicts Inferior Survival in Pgi-DLBCL Treated with CHOP-like Regimen/Rituximab

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5404-5404 ◽  
Author(s):  
Le Zhang ◽  
Bing Xia ◽  
Shanqi Guo ◽  
Xiaowu Li ◽  
Fulian Qu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Chemotherapy Response ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Expression Levels ◽  
Stage Disease

Abstract MYC protein expression has been identified to be associated with inferior overall survival (OS) and progression-free survival (PFS) when coexpressed with BCL-2 protein in patients with diffuse large B cell lymphoma (DLBCL). But the concurrent expression of MYC and BCL-2 proteins in primary gastrointestinal (PGI)-DLBCL has not been clearly understood. Here, we investigated whether this coexpression has prognostic significance in PGI-DLBCL patients and explored its associations with patients’ clinical parameters. We enrolled 60 PGI-DLBCL patients and 30 age- and sex-matched healthy controls. Expression levels of MYC and BCL-2 were detected from both protein and mRNA levels by immunohistochemistry and real-time RT-PCR. Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein were correlated with high MYC and BCL-2 mRNA expression, respectively (both p<0.05). We found that patients with advanced-stage disease (at IIE-IV) having higher MYC and BCL-2 coexpression levels (p<0.05). In addition, MYC+/BCL-2+ patients had more difficulty achieving complete remission than others (p<0.05). Presence of MYC protein expression only affected OS and PFS when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (p<0.05) even after adjusting for age, Lugano stage, IPI, and BCL-2 protein expression in a multivariable model. MYC+/BCL-2+ patients have poorer chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting prognosis of PGI-DLBCL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status

2019 ◽  
Vol 32 (6) ◽  
pp. 866-883 ◽  
Author(s):  
Maarit Ahtiainen ◽  
Erkki-Ville Wirta ◽  
Teijo Kuopio ◽  
Toni Seppälä ◽  
Juha Rantala ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Prognostic Value ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Mismatch Repair Status
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