Screening for microsatellite instability in colorectal carcinoma: Practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting.

Screening for microsatellite instability in colorectal carcinoma: Practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting. Malays J Pathol. 2019 Aug;41(2):91-100 Authors: Cheah PL, Li J, Looi LM, Koh CC, Lau TP, Chang SW, Teoh KH, Mun KS, Nazarina AR Abstract Since 2014, the National Comprehensive Cancer Network (NCCN) has recommended that colorectal carcinoma (CRC) be universally tested for high microsatellite instability (MSI-H) which is present in 15% of such cancers. Fidelity of resultant microsatellites during DNA replication is contingent upon an intact mismatch repair (MMR) system and lack of fidelity can result in tumourigenesis. Prior to commencing routine screening for MSI-H, we assessed two commonly used methods, immunohistochemical (IHC) determination of loss of MMR gene products viz MLH1, MSH2, MSH6 and PMS2 against PCR amplification and subsequent fragment analysis of microsatellite markers, BAT25, BAT26, D2S123, D5S346 and D17S250 (Bethesda markers) in 73 unselected primary CRC. 15.1% (11/73) were categorized as MSI-H while deficient MMR (dMMR) was detected in 16.4% (12/73). Of the dMMR, 66.7% (8/12) were classified MSI-H, while 33.3% (4/12) were microsatellite stable/low microsatellite instability (MSS/MSI-L). Of the proficient MMR (pMMR), 95.1% (58/61) were MSS/MSI-L and 4.9% (3/61) were MSI-H. The κ value of 0.639 (standard error =0.125; p = 0.000) indicated substantial agreem...
Source: Malaysian Journal of Pathology - Category: Pathology Tags: Malays J Pathol Source Type: research

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ConclusionFurther studies should be conducted to provide new insights about survival of colorectal carcinoma in Lynch syndrome, as well as the therapeutic alternatives for this neoplasia.ResumoIntroduçãoO carcinoma colorretal é a terceira neoplasia mais prevalente no mundo, bem como a segunda causa de morte por câncer. A maioria destas neoplasias são esporádicas, devidas a mutações somáticas, mas cerca de 15% são hereditárias como a síndrome de Lynch ou Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Apesar de ser a mesma neoplasia, esta ...
Source: Journal of Coloproctology - Category: Gastroenterology Source Type: research
Abstract MMR-deficient colorectal cancers (dMMR CRC) are characterized by the expression of highly-immunogenic neoantigen peptides, which stimulate lymphocytic infiltration as well as up-regulation of inflammatory cytokines. These features are key to understanding why immunotherapy (specifically PD-1 and/or CTLA-4 checkpoint blockade) has proved to be highly effective for the treatment of patients with advanced dMMR CRC. Importantly, pre-clinical studies also suggest that this correlation between potent tumor neoantigens and the immune microenvironment is present in early (pre-malignant) stages of dMMR colorectal ...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
We present a patient who received nivolumab for heterogeneity of right-sided metastatic colon carcinoma. Intervention: The patient was treated with nivolumab combined with chemotherapy. Outcome: The computed tomography showed mass lesion in the left lobe of liver remained stable while metastasis tumors under envelop of liver were exacerbated after 6 cycles of nivolumab combined with chemotherapy, and later regressed. Lessons: The status of mismatch repair in primary tumor and metastatic liver carcinoma is contradictory but using nivolumab demonstrated encouraging efficacy. This is the first case of pseudo progress...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
GBM is the most aggressive form of brain cancer. The current standard of care against GBM is a combination of surgery, chemotherapy and radiotherapy. However, after standard treatment, the cancer usually recurs – emphasizing a need for new targets and better alternatives. A promising target is cyclin-dependent kinase 5 (CDK5), the hyperactivity of which has been shown to have a role in cancer progression. TP5/TFP5, a small peptide inhibitor against CDK5, was developed at the National Institutes of Health and modified to increase its passage through the blood brain barrier. Researchers at the NCI and NINDS demons...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
ConclusionsTraditionally, patients with vesicovaginal fistula after pelvic radiation therapy and multiple abdominal surgeries are managed by laparotomy. This video demonstrates a feasible robotic approach to vesicovaginal fistula repair, with superior imaging affording a three-dimensional vision and stabilization of instruments allowing wrist-like movements.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
Abstract BACKGROUND: Different histological growth patterns (HGPs) of colorectal carcinoma (CRC) liver metastasis are associated with patients' prognosis and response to antiangiogenic therapy. However, the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established. AIM: To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis. METHODS: A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups: ...
Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Lynch Syndrome (LS) entails a defective DNA mismatch repair system, which is the post-replicative proofreading and editing system, ensuring our genome's integrity. LS predisposes to several cancers, most commonly colorectal and endometrial cancers. LS occurs in approximately 1 in 250 –1,000 people.LS is associated with urological malignancies with upper tract urothelial carcinoma the most common, although still clinically underestimated. Other urologic malignancies possibly associated with LS include bladder, prostate, testis, and renal cell carcinoma.
Source: Urology - Category: Urology & Nephrology Authors: Source Type: research
Abstract A common strategy to overcome acquired chemotherapy resistance is the combination of a specific anticancer drug (e.g., topoisomerase I inhibitor irinotecan) together with a putative sensitizer. The purpose of this study was to analyze the cytostatic/cytotoxic response of colorectal carcinoma (CRC) cells to irinotecan, depending on the mismatch repair (MMR) and p53 status and to examine the impact of BV6, a bivalent antagonist of inhibitors of apoptosis c-IAP1/c-IAP2, alone or combined with irinotecan. Therefore, several MSH2- or MSH6-deficient cell lines were complemented for MMR deficiency, or MSH6 was k...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research
ConclusionThe results reveal the frequency of these biomarkers in different malignancies, with potential implications for PD ‐1/PD‐L1 blockade use for Chinese patients with cancer.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Conclusion: We report a novel mutation STK11 (p.G270W), in medullary carcinoma of the colon with an associated mucinous component.
Source: Cancer Genomics and Proteomics - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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