Molecular Pathology of Colorectal Cancer

Colorectal cancer (CRC) is the third most commonly diagnosed cancer. This review gives an overview of the current knowledge of molecular mechanisms of colorectal carcinogenesis and the role of molecular testing in the management of CRC. The majority of CRCs arise from precursor lesions such as adenoma, transforming to adenocarcinoma. Three molecular carcinogenesis pathways have been identified; (1) chromosomal instability, (2) microsatellite instability (MSI), and (3) CpG island methylator phenotype, each account for ~85%, 15%, and 17%, respectively. Evaluation of MSI status, extended RAS mutation analysis, and BRAF mutation analysis are recommended by the guideline published by joint effort from professional societies. MSI testing is important for identification of Lynch syndrome patients and prognostic and predictive markers. Extended RAS testing is an important predictive marker for antiepidermal growth factor receptor therapy. BRAF p.V600 mutation status can be used as prognostic marker, but not predictive marker for antiepidermal growth factor receptor therapies. Emerging technologies utilizing high throughput sequencing have introduced novel biomarkers and testing strategies. Tumor mutation burden predicts immunotherapy response in addition to MSI status. Liquid biopsy can be utilized when adequate tissue sample is not available or for monitoring therapy response. However, assay standardization and guidelines and recommendations for utilization of these assay will be ne...
Source: Advances in Anatomic Pathology - Category: Pathology Tags: Review Articles Source Type: research

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ConclusionTo optimize targeting and visualization of the surgical field in right pelvic sidewall/paracolic gutter, robotic arms can be placed in a straight line from above the pubic symphysis extending to the left subcostal line and between the midline vertical and midclavicular lines. Robotic tumor debulking should be considered in selected patients with recurrent ovarian cancer who present with oligo-metastatic disease, in the absence of carcinomatosis.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
ConclusionsThe ‘pelvis-first’ approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5
Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
ConclusionWe show that low ‐level mosaicism can be detected by using high‐coverage targeted NGS panels on constitutional and/or tumor DNA. This report illustrates that by using sensitive sequencing techniques, more cases of genetic diseases driven by mosaic mutations may be identified, with important clinical consequences for patients and family members.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Case Summary: A 56-year-old man with a history of hypertension and hyperlipidemia was referred by gastroenterology for bleeding per rectum. Because of a family history of colon cancer, he had several prior colonoscopies, most recently 3 years ago, without evidence of pathology. His mother was diagnosed with colon cancer in her mid-40s. His current colonoscopy demonstrated a 2.4 × 1.5 cm cecal adenocarcinoma. Staging workup revealed no evidence of metastatic disease. Because of the patient’s family history, the specimen was further evaluated and found to have high microsatellite instabilit...
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Resident’s Corner Source Type: research
Abstract Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. However, screening may be beneficial for individuals with familial history, chronic diseases with genetic predispositions, or inherited cancer...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. However, screening may be beneficial for individuals with familial history, chronic diseases with genetic predispositions, or inherited cancer syndromes, such a...
Source: American Journal of Pathology - Category: Pathology Authors: Tags: Review Source Type: research
We report a case of a patient with colorectal cancer referred to our medical genetics department for molecular analysis and genetic counseling. The proband is a 64-year-old woman diagnosed with a tumor of the cecum. Histopathological examination showed a moderately differentiated mucinous adenocarcinoma categorized by pT3 N0. Analysis of her pedigree revealed three siblings who had colon cancer, as well as one relative with brain cancer. Based on these findings, molecular genetic investigation was found to be necessary in order to identify the disease-causing mutation. Immunohistochemistry staining of MMR proteins was perf...
Source: The Turkish Journal of Gastroenterology - Category: Gastroenterology Authors: Tags: Turk J Gastroenterol Source Type: research
We report here a 16-year-old patient who presented initially with symptoms characteristic of appendicitis. Following a CT scan suggesting perforated appendicitis, the patient was treated with intravenous antibiotics with a scheduled interval appendectomy three months later. Pathology reports from the interval appendectomy showed that the specimen contained a well-to-moderately differentiated adenocarcinoma. The patient then underwent robot assisted right hemicolectomy as definitive management, which demonstrated that the tumor originated in the cecum with invasion into the submucosa and focally infiltrating the muscularis ...
Source: Journal of Pediatric Surgery Case Reports - Category: Surgery Source Type: research
Conclusion: When compared to prior reports, this study suggests a lower frequency of MSI among the Puerto Rican population. The higher prevalence of MLH1 mutations correlates with previous studies of protein expression among the Hispanic community including Colombian, Uruguay and Brazilian populations.
Source: Cancer Genomics and Proteomics - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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