Validation of microsatellite instability histology scores with Bethesda guidelines in hereditary nonpolyposis colorectal cancer

Kaya, Mustafa; Başak, Fatih; Şişik, Abdullah; Hasbahçeci, Mustafa; Baş, Gürhan; Ali̇moğlu, Orhan; Topal, Cumhur Selçuk; Kır, Gözde

doi:10.4103/0973-1482.174558

Cited by 3 publications

(2 citation statements)

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“…Other histological features documented included tumour infiltrating lymphocytes, Crohn-like lymphocytic reaction, dirty necrosis and tumour staging. The tumour infiltrating lymphocytes was determined as presence of 2 or 3 intra-epithelial lymphocytes per 5 high power fields while Crohn-like lymphocytic reaction was determined as presence of 2 to 3 peri-or intra-tumoural lymphocytic follicle aggregates with or without a germinal center [11,12]. Dirty necrosis was defined as the presence of tumour glandular luminal eosinophilic secretions mixed with necrotic debris and neutrophilic infiltrate [13].…”

Section: Plos Onementioning

confidence: 99%

Cyclooxygenase-2 expression in colorectal carcinoma, adenomatous polyps and non-tumour bearing margins of resection tissues in a cohort of black Africans

et al. 2021

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Background Emerging data suggest a negative role of cyclooxygenase-2 (COX-2) in colorectal carcinomas (CRC). Investigating this in developing communities such as ours helps to contribute to existing understanding of these lesions. Methods and findings Formalin-fixed paraffin-embedded CRC colectomy tissues and their corresponding non-tumour margins of resected tissues were sectioned and stained with COX-2 antibody. Adenomatous polyp tissues from non-cancer bearing individuals were similarly processed for comparison. COX-2 expression was scored for percentage (< 5% = 0; 6%-25% = 1; 26%-50% = 2; 51%-75% = 3; 76%-100% = 4) and intensity (no staining = 0; yellow = 2; yellowish-brown = 3, brown = 4). Total immunoscore (percentage + intensity score) ≥ 2 was regarded as positive COX-2 expression. Outcome was statistically evaluated with clinicopathological data to determine COX-2 expression-associated and predictor variables. Ninety-five CRC cases and 27 matched non-tumour tissues as well as 31 adenomatous polyps met the inclusion criteria. Individuals with CRC had a mean age of 56.1 ± 12.6 years while those with adenomatous polyps had a median age of 65 years (range 43–88). COX-2 was differentially overexpressed in CRCs (69/95; 72.6%) and in adenomatous polyps (17/31; 54.8%) than in non-tumour tissues 5/27 (18.5%); p < 0.001). The difference in COX-2 expression between CRC and polyps was non-significant (p > 0.065). Tumour grade, advanced pT-stage, tumour-infiltrating lymphocytes, and dirty necrosis were also significantly associated with COX-2 expression (p < 0.035; 0.043, 0.035 and 0.004, respectively). Only dirty necrosis and Crohns-like lymphocytic aggregates predicted COX-2 expression (p < 0.05). Conclusion This study showed a progressive increase in COX-2 expression from normal to adenomatous polyp and CRC tissues, this being associated with poorer prognostic indicators. Although COX-2 appears early in CRC, it may play a secondary role in promoting tumour growth and invasiveness.

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Section: Plos Onementioning

confidence: 99%

Cyclooxygenase-2 expression in colorectal carcinoma, adenomatous polyps and non-tumour bearing margins of resection tissues in a cohort of black Africans

et al. 2021

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“…CRC with dMMR has characteristic phenotype features including predominant proximal location, mostly poor differentiation, mucinous and lymphocyte deposition in the tumor and surrounding areas (Crohn-like cancer) ( Thibodeau et al, 1993 ; Miyakura et al, 2001 ; Søreide et al, 2009 ). MSI-H/dMMR CRCs are associated with lack of responsiveness to conventional chemotherapy and there was a lack of benefit from adjuvant five FU-based chemotherapy in patients with stage II or III MSI-H/dMMR CRC ( Hutchins et al, 2010 ; Kaya et al, 2017 ; Sargent et al, 2010 ; Paulose et al, 2019 ). Therefore, it is recommended to perform MSI testing as a routine examination to predict prognosis and therapeutic response to chemotherapy in the patients with CRC.…”

Section: Introductionmentioning

confidence: 99%

Detection of Microsatellite Instability in Colorectal Cancer Patients With a Plasma-Based Real-Time PCR Analysis

Kim

Lee

et al. 2021

Front. Pharmacol.

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A microsatellite instability (MSI) test is crucial for screening for HNPCC (Hereditary nonpolyposis colorectal cancer; Lynch syndrome) and optimization of colorectal cancer (CRC) treatment. Mismatch repair (MMR) deficiency is a predictor for good response of immune checkpoint inhibitors in various malignancies. In this study, we evaluated the results of a newly developed plasma-based real-time PCR kit for the detection of MSI in CRC patients. We assessed a peptide nucleotide acid (PNA) probe-mediated real-time PCR test (U-TOP MSI Detection Kit Plus) that determines MSI status by using amplicon melting analysis of five markers (NR21, NR24, NR27, BAT25, and BAT26) from plasma. Eighty-four CRC patients (46 dMMR and 38 pMMR) with colorectal cancer were analyzed. The concordance rate of MSI status assessment between the plasma kit and IHC was 63.0% in dMMR patients (29/46), but in the pMMR evaluation, a 100% (38/38) concordance rate was observed. In the evaluation of the performance of a custom tissue U-TOP MSI Detection Kit and plasma kit in 28 patients, sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) of plasma kit were 68.4, 100, 100, and 44.4%, respectively, with the tissue U-TOP MSI Detection Kit. Our results demonstrate the feasibility of a non-invasive and rapid plasma-based real-time PCR kit (U-TOP MSI Detection Kit Plus) for the detection of MSI in colorectal cancer.

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Cáncer de colon en Colombia, fenotipo molecular: tamizaje para síndromes con agregación familiar

Bohórquez

Criollo

Carmona

et al. 2019

RVACCB

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Objetivo: Caracterizar las características clínico-patológicas y algunos fenotipos moleculares del cáncer colorrectal (CCR), en 1278 pacientes de la región andina colombiana. Métodos: Se analizó una muestra de 1278 pacientes con CCR. Análisis de expresión de los genes MMR-Mismatch Repair-hMLH1, utilizando métodos inmunohistoquímicos (IHC). Para inestabilidad microsatelital-MSI se utilizó ADN de tejido tumoral-normal mediante PCR. Resultados: Promedio de edad 57,4 años, la enfermedad es más frecuente en el género femenino 53,2%. La frecuencia de pacientes menores de 50 años (26,5%) es mayor a la esperada, el CCR en estos casos se asoció a tipos histológicos agresivos -carcinoma mucinoso y carcinoma en anillo de sello- p=<0,000, los cuales, a su vez, resultaron asociados a inestabilidad microsatelital (MSI-H). La localización más frecuente: recto (31,1%), p=0,002, el diagnóstico se produjo en estados avanzados de la enfermedad T3-T4 (75,1%) p=0,022. Tipo histológico más frecuente: adenocarcinoma. La sensibilidad del análisis inmunohistoquímico de MLH1 para la detección de MSI+, fue de 71% (CI: 49 - 87). El análisis por IHC-MLH1 en 575 casos mostró pérdida de la expresión en el 7% de los pacientes. Las pruebas de MSI se realizaron en 451 casos de CCR; el 23% presentaron alta inestabilidad microsatelital (MSI-H). Conclusión: La determinación de inestabilidad microsatelital y la inmunohistoquímica para MMR permiten identificar pacientes en riesgo de ser portadores de mutaciones relacionadas con síndrome de Lynch en pacientes colombianos.

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Validation of microsatellite instability histology scores with Bethesda guidelines in hereditary nonpolyposis colorectal cancer

Abstract: The MSI scoring systems, MsPath, and PathScore, are reliable systems and effectively correlated with BG for predicting patients who need advanced analysis techniques because of the risk of HNPCC.

Cited by 3 publications

References 2 publications

Cyclooxygenase-2 expression in colorectal carcinoma, adenomatous polyps and non-tumour bearing margins of resection tissues in a cohort of black Africans

Cyclooxygenase-2 expression in colorectal carcinoma, adenomatous polyps and non-tumour bearing margins of resection tissues in a cohort of black Africans

Detection of Microsatellite Instability in Colorectal Cancer Patients With a Plasma-Based Real-Time PCR Analysis

Cáncer de colon en Colombia, fenotipo molecular: tamizaje para síndromes con agregación familiar

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