scholarly journals PD-L1 Expression Is Associated with Deficient Mismatch Repair and Poor Prognosis in Middle Eastern Colorectal Cancers

2021 ◽  
Vol 11 (2) ◽  
pp. 73
Author(s):  
Abdul K. Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Padmanaban Annaiyappanaidu ◽  
Wael Haqawi ◽  
Maha Al-Rasheed ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Poor Prognosis ◽  
Middle Eastern ◽  
Prognostic Significance ◽  
Mucinous Histology ◽  
Programmed Death ◽  
Mmr Deficiency ◽  
Independent Marker ◽  
Deficient Mismatch Repair ◽  
Large Retrospective Study

Several clinical trials are investigating the use of immune-targeted therapy with Programmed death ligand-1 (PD-L1) inhibitors for colorectal cancer (CRC), with promising results for patients with mismatch repair (MMR) deficiency or metastatic CRC. However, the prognostic significance of PD-L1 expression in CRC is controversial and such data are lacking in CRC from Middle Eastern ethnicity. We carried out this large retrospective study to investigate the prognostic and clinico-pathological impact of PD-L1 expression in Middle Eastern CRC using immunohistochemistry. A total of 1148 CRC were analyzed for PD-L1 expression. High PD-L1 expression was noted in 37.3% (428/1148) cases and was correlated with aggressive clinico-pathological features such as high malignancy grade (p < 0.0001), larger tumor size (p = 0.0007) and mucinous histology (p = 0.0005). Interestingly, PD-L1 expression was significantly higher in patients exhibiting MMR deficiency (p = 0.0169) and BRAF mutation (p = 0.0008). Furthermore, the expression of PD-L1 was found to be an independent marker for overall survival (HR = 1.45; 95% CI = 1.06–1.99; p = 0.0200). In conclusion, the results of this study indicate that PD-L1 expression could be a valid biomarker for poor prognosis in Middle Eastern CRC patients. This information can help in decision-making for anti-PD-L1 therapy in Middle Eastern CRC, especially for patients with MMR deficient tumors.

scholarly journals PD‐L1 Expression is Associated with Deficient Mismatch Repair and Poor Prognosis in Middle Eastern Colorectal Cancers

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Khawla Al‐Kuraya ◽  
Abdul Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Padmanaban Annaiyappanaidu ◽  
Wael Haqawi ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Poor Prognosis ◽  
Middle Eastern ◽  
Colorectal Cancers ◽  
Deficient Mismatch Repair

scholarly journals Does mismatch repair (MMR) deficiency have prognostic significance in low-risk endometrioid endometrial cancers?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17122-e17122
Author(s):  
Soyoun Rachel Kim ◽  
Annick Pina ◽  
Arianne Albert ◽  
Jessica N. McAlpine ◽  
Robert Wolber ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Prognostic Significance ◽  
Cox Proportional Hazards Model ◽  
Low Risk ◽  
Recurrence Rates ◽  
Significant Difference ◽  
Stage Ia ◽  
Endometrial Cancers ◽  
Mmr Deficiency

e17122 Background: Mismatch repair (MMR) deficiency is observed in 25-30% of all endometrial cancers. This can be detected by the absence of MMR protein staining on immunohistochemistry (IHC), and is used in many jurisdictions as a screen for an inherited mutation in one of the MMR genes (Lynch Syndrome). Only 10% of women with MMR deficiency (MMRd) have Lynch syndrome, but MMRd may still have prognostic significance. The objective of this study was to compare clinical outcomes between MMR deficient and proficient low-risk endometrioid endometrial cancers (stage IA, grade 1/2). Methods: This was a retrospective population-based cohort study of all low-risk endometrial cancers from Vancouver Coastal Health authority region from 2011 to 2016 that were assessed for MMR deficiency (MMRd). Primary outcome measures were recurrence rates expressed per person-years (py), progression free survival (PFS) and overall survival (OS) calculated using Kaplan-Meier method and log-rank tests. Cox proportional hazards model estimated the association between MMRd and recurrence and death after adjustment for covariates, expressed as hazard ratios (HR). Results: There were 475 low-risk patients, including 131 MMRd (27.6%) and 345 MMRp (proficient) patients. Women with MMRd tumors had higher recurrence rates (3.53p100py vs 1.21p100py) and worse PFS (p = 0.0082) compared to women with MMRp tumors. After adjustment for age, LVSI status, adjuvant therapy, and post-operative grade, MMRd status remained associated with a higher risk of recurrence (HR 2.99, 95% CI 1.27-7.04). There was no significant difference in OS between MMR groups (HR 1.38, 95% CI 0.57-3.33). Conclusions: In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, MMR deficiency is associated with a higher recurrence rate than in MMR proficient cases, after adjustment for covariates, implying that MMR deficiency reflects a different biology in endometrial cancer.

scholarly journals Prognostic implications of mismatch repair deficiency in patients with nonmetastatic colorectal and endometrial cancer

ESMO Open ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. e000474 ◽  
Author(s):  
Elena Fountzilas ◽  
Vassiliki Kotoula ◽  
George Pentheroudakis ◽  
Kyriaki Manousou ◽  
Genovefa Polychronidou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Prognostic Significance ◽  
Primary Outcome Measure ◽  
Mucinous Component ◽  
Repair Deficiency ◽  
Improved Outcomes ◽  
Mmr Deficiency

BackgroundThe clinical relevance of mismatch repair (MMR) status in patients with nonmetastatic cancer across tumour types remains unclear. Our goal was to investigate the prognostic role of MMR deficiency in patients with stage I-III colorectal and endometrial cancer.MethodsPatients with nonmetastatic colorectal and endometrial cancer with tumour tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)’s tumour repository. Patients had been referred to Departments of Medical Oncology affiliated with HeCOG. MMR protein expression was evaluated by immunohistochemistry. The primary outcome measure was overall survival (OS).ResultsFrom May 1990 to September 2012, 1158 patients with nonmetastatic colorectal (N = 991) and endometrial cancer (N = 167) were identified (median age: 64 years, men: 544). All patients with colorectal and 109 (65%) with endometrial cancer had received adjuvant treatment. MMR deficiency was observed in 114 (11.5%) of colorectal and 80 (47.9%) of endometrial tumours. More commonly deficient proteins were PMS2 (69 patients, 7%) and MLH1 (63 patients, 6.5%) in colorectal cancer and MSH2 (58 patients, 34.7%) in endometrial cancer. Colorectal MMR-deficient (dMMR) tumours were more likely to be right sided (65 % dMMR vs 27 % proficient MMR, pMMR; p < 0.001), high grade (31% vs 15%, χ2, p < 0.001) and with a mucinous component (64% vs 42%, p < 0.001). Endometrial dMMR tumours were more often of endometrioid histology (51.4 % endometrioid vs 20 % serous/clear cell, p = 0.020). Compared with MMR proficiency, MMR deficiency was associated with improved OS in patients with endometrial cancer (HR = 0.38, 95% CI 0.20 to 0.76, p = 0.006), but not in patients with colorectal cancer (HR = 0.73, 95% CI 0.49 to 1.09, p = 0.130). After adjusting for age, stage and grade, MMR deficiency maintained its favourable prognostic significance in patients with endometrial cancer (HR = 0.42, 95% CI 0.20 to 0.88, p = 0.021).ConclusionsDMMR was associated with improved outcomes in patients with nonmetastatic endometrial cancer, but not in patients with nonmetastatic colorectal cancer who received adjuvant chemotherapy.

scholarly journals Prognostic significance of bone marrow FDG uptake in patients with gynecological cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kotaro Shimura ◽  
Seiji Mabuchi ◽  
Naoko Komura ◽  
Eriko Yokoi ◽  
Katsumi Kozasa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Poor Prognosis ◽  
Gynecological Cancer ◽  
Prognostic Significance ◽  
Standardized Uptake Value ◽  
Suppressor Cells ◽  
Underlying Mechanism ◽  
Fdg Uptake

AbstractWe investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.

scholarly journals Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3124
Author(s):  
Mikko Loukovaara ◽  
Annukka Pasanen ◽  
Ralf Bützow
Keyword(s):  
Risk Factors ◽  
Mismatch Repair ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
New Therapeutic Approaches ◽  
Increased Risk ◽  
Mmr Deficiency ◽  
Endometrial Carcinomas ◽  
Risk Of Cancer

The aggressiveness of mismatch repair (MMR) deficient endometrial carcinomas was examined in a single institution retrospective study. Outcomes were similar for MMR proficient (n = 508) and deficient (n = 287) carcinomas, identified by immunohistochemistry. In accordance with molecular classification based on The Cancer Genome Atlas (TCGA), tumors with abnormal p53 staining or polymerase-ϵ exonuclease domain mutation were excluded from the MMR proficient subgroup, termed as “no specific molecular profile” (NSMP). Compared with NSMP (n = 218), MMR deficiency (n = 191) was associated with poor disease-specific survival (p = 0.001). MMR deficiency was associated with an increased risk of cancer-related death when controlling for confounders (hazard ratio 2.0). In the absence of established clinicopathologic risk factors, MMR deficiency was invariably associated with an increased risk of cancer-related death in univariable analyses (hazard ratios ≥ 2.0). In contrast, outcomes for MMR deficient and NSMP subgroups did not differ when risk factors were present. Lymphatic dissemination was more common (p = 0.008) and the proportion of pelvic relapses was higher (p = 0.029) in the MMR deficient subgroup. Our findings emphasize the need for improved triage to adjuvant therapy and new therapeutic approaches in MMR deficient endometrial carcinomas.

scholarly journals Cytoplasmic LXR expression is an independent marker of poor prognosis for patients with early stage primary breast cancer

2021 ◽  
Author(s):  
Wanting Shao ◽  
Christina Kuhn ◽  
Doris Mayr ◽  
Nina Ditsch ◽  
Magdalena Kailuwait ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Poor Prognosis ◽  
Early Stage ◽  
Clinicopathological Characteristics ◽  
Clinicopathological Parameters ◽  
Liver X Receptors ◽  
X Receptors ◽  
Independent Marker ◽  
Overall Survival Analysis

Abstract Purpose The aim of this study was to investigate the expression of liver X receptors α/β (LXR) in primary breast cancer (BC) tissues and to analyze its correlations with clinicopathological parameters including patient survival. Methods In a well-characterized cohort of 305 primary BC, subcellular distribution of LXR was evaluated by immunohistochemistry. Correlations with clinicopathological characteristics as well as with patient outcome were analyzed. Results LXR was frequently localized in both nuclei and cytoplasms of BC cells, with stronger staining in nuclei. Total and nuclear LXR expression was positively correlated with ER and PR status. Overall survival analysis demonstrated that cytoplasmic LXR was significantly correlated with poor survival and appeared as an independent marker of poor prognosis, in stage I but not in stage II–III tumors Conclusion Altogether, these data suggest that cytoplasmic LXR could be defined as a prognostic marker in early stage primary BC.

Microsatellite frameshift variants in SGO1 of gastric cancer are not always associated with MSI status

2020 ◽  
pp. jclinpath-2020-206934
Author(s):  
Tomohiro Sugiyama ◽  
Moriya Iwaizumi ◽  
Terumi Taniguchi ◽  
Satoshi Suzuki ◽  
Shinya Tani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Gastrointestinal Cancer ◽  
Early Stage ◽  
Stage Iv ◽  
Cancer Resection ◽  
Deficient Mismatch Repair ◽  
Gastric Cancer Resection ◽  
Genemapper Software

AimsAlthough frameshift variants in the microsatellite area of shugoshin 1 (SGO1) have been reported in the context of microsatellite instability-high (MSI-H)/deficient mismatch repair gastrointestinal cancer, most have been evaluated only in early stage I–III patients, and only two of its five microsatellite regions have been evaluated. Therefore, we investigated the frequency and MSI status of microsatellite frameshift variants in gastric cancer cases, including stage IV.MethodsIn a total of 55 cases, 30 gastric cancer resection and 25 non-resection cases, DNA was extracted from both tumour and normal parts and PCR was performed. The variant was confirmed by TA cloning, and MSI was evaluated using GeneMapper software.ResultsA frameshift variant of c.973delA was observed in 16 of the 45 evaluable cases. Its frequency was 35.6%. Of the 25 cases that could be assessed for MSI status, two cases of MSI-H were associated with the c.973delA SGO1 variant. However, c.973delA SGO1 variant was also observed in four cases of microsatellite stable.ConclusionOur study shows that SGO1 frameshift variants are not always associated with MSI status.

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.

Sign in / Sign up

Export Citation Format

Share Document