Interpretation of Mismatch Repair Protein Immunohistochemistry in Endometrial Carcinoma Should Consider Both Lynch Syndrome Screening and Immunotherapy Susceptibility: An Illustrative Case Report
We present an instructive case of FIGO grade 1 endometrioid endometrial carcinoma with a biphasic morphology, corresponding to subclonal loss of mismatch repair proteins (MMRP) MLH1 and PMS2 by immunohistochemistry and subclonal microsatellite instability. A pulmonary metastasis represented only the tumor component with retention of MMRPs. This case illustrates the need for pathologists to recognize and report heterogenous expression of MMRPs in endometrial carcinoma, to consider tumor heterogeneity when selecting foci for molecular studies, and to re-evaluate MMRP expression in tumor metastases, when clinically indicated....
Source: International Journal of Gynecological Pathology - April 8, 2020 Category: Pathology Tags: PATHOLOGY OF THE CORPUS: CASE REPORTS Source Type: research

Clinically applicable cases of anti-programmed cell death protein 1 immunotherapy for colorectal cancer patients
AbstractWe investigated the prevalence and characteristics of defective mismatch repair (dMMR) in colorectal cancer (CRC) patients who would potentially benefit from anti-programmed cell death protein 1 (PD-1) immunotherapy. Medical records were obtained and reviewed for 1147 patients who underwent surgical resection of stage I –IV CRC, in whom universal screening for Lynch syndrome using immunohistochemistry for MMR proteins had been undertaken. The molecular characteristics of dMMR CRCs were also investigated. Defective MMR accounted for 5.2% of stage I–IV CRC patients, including 12 (1.0% of all CRC patients)...
Source: Surgery Today - April 6, 2020 Category: Surgery Source Type: research

Advances in Hereditary Colorectal Cancer: Opportunities and Challenges for Clinical Translation
AbstractPurpose of ReviewOver the last decade, tremendous progress has been made in our understanding, clinical evaluation, and management of hereditary colorectal cancer (CRC). This review provides an overview of recent developments and highlights opportunities and future challenges for clinical translation.Recent FindingsNovel genes have been identified associated with predisposition to CRC and polyposis including,POLE,POLD1,NTHL1,MSH3, andRNF43. Genetic testing has transitioned from phenotype-specific single-gene testing to multigene panels, and universal screening programmes for Lynch syndrome (LS) have been widely imp...
Source: Current Genetic Medicine Reports - April 3, 2020 Category: Genetics & Stem Cells Source Type: research

Associations Between Mutations in MSH6 and PMS2 and Risk of Surveillance-detected Colorectal Cancer
Lynch syndrome is the most common inherited cause of colorectal cancer (CRC). Contemporary and mutation-specific estimates of CRC-risk in patients undergoing colonoscopy would optimize surveillance strategies. We performed a prospective national cohort study, using data from New Zealand, to assess overall and mutation-specific risk of CRC in patients with Lynch syndrome undergoing surveillance. (Source: Clinical Gastroenterology and Hepatology)
Source: Clinical Gastroenterology and Hepatology - March 31, 2020 Category: Gastroenterology Authors: Mehul Lamba, Chris Wakeman, Rosy Ebel, Sarah Hamilton, Chris Frampton, Maxene Kiesanowski, Ben Griffiths, John Keating, Susan Parry, Teresa Chalmers-Watson Source Type: research

Increased Risk of Acute Myelogenous Leukemia After Early Onset but Not Late-Onset Colorectal Cancer
Conclusion: These observations suggest that early onset colorectal cancer and AML may be related diseases. (Source: American Journal of Clinical Oncology)
Source: American Journal of Clinical Oncology - March 27, 2020 Category: Cancer & Oncology Tags: Original Articles: Gastrointestinal Source Type: research

Structure of the Mucosal and Stool Microbiome in Lynch Syndrome.
Abstract The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosa...
Source: Cell Host and Microbe - March 26, 2020 Category: Microbiology Authors: Yan Y, Drew DA, Markowitz A, Lloyd-Price J, Abu-Ali G, Nguyen LH, Tran C, Chung DC, Gilpin KK, Meixell D, Parziale M, Schuck M, Patel Z, Richter JM, Kelsey PB, Garrett WS, Chan AT, Stadler ZK, Huttenhower C Tags: Cell Host Microbe Source Type: research

DR ROBERT CIMA (Rochester, MN): The authors present a single-institution experience of patients with genetically confirmed Lynch syndrome, who underwent segmental colectomy as treatment for index colon cancer. The natural history of these patients is not well described in the literature, and it suggests it is tied to their underlying genetic profile. (Source: Journal of the American College of Surgeons)
Source: Journal of the American College of Surgeons - March 24, 2020 Category: Surgery Tags: Southern surgical association article Source Type: research

Issue highlights
Lynch syndrome is the most common inherited cause of gastrointestinal cancer. Although current guidelines recommend endoscopic screening for gastric cancer and Helicobacter pylori infection in carriers of germline variants causing Lynch syndrome, there are limited data to support these recommendations. (Source: Clinical Gastroenterology and Hepatology)
Source: Clinical Gastroenterology and Hepatology - March 24, 2020 Category: Gastroenterology Authors: Vincent Wong Tags: Issue Highlights Source Type: research

Correction: Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
The original version of this article unfortunately contained a mistake. The variants listed in Table 3 of the original version of this article are not in line with the latest HGVS (Human Genome Variation Society) nomenclature (version 19.01). (Source: Journal of Gastrointestinal Cancer)
Source: Journal of Gastrointestinal Cancer - March 24, 2020 Category: Cancer & Oncology Source Type: research

Genes, Vol. 11, Pages 325: A Novel Germline MLH1 In-Frame Deletion in a Slovenian Lynch Syndrome Family Associated with Uncommon Isolated PMS2 Loss in Tumor Tissue
Gazič Krajc Novaković The diagnostics of Lynch syndrome (LS) is focused on the detection of DNA mismatch repair (MMR) system deficiency. MMR deficiency can be detected on tumor tissue by microsatellite instability (MSI) using molecular genetic test or by loss of expression of one of the four proteins (MLH1, MSH2, MSH6, and PMS2) involved in the MMR system using immunohistochemistry (IHC) staining. According to the National Comprehensive Cancer Network (NCCN) guidelines, definitive diagnosis of LS requires the identification of the germline pathogenic variant in one of the MMR genes. In the report, we are presen...
Source: Genes - March 18, 2020 Category: Genetics & Stem Cells Authors: Klan čar Blatnik Šetrajčič Dragoš Vogri č Stegel Blatnik Drev Gazi č Krajc Novakovi ć Tags: Article Source Type: research

Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience.
CONCLUSIONS: BRCA1 carriers have the highest risk of occult neoplasia at RRSO, and the frequency increased with age. Women with BRCA1/2 mutations often have RRSO beyond recommended ages. One PALB2 carrier had FT intraepithelial neoplasia, a novel finding. Serial sectioning is critical to identifying occult neoplasia and should be performed for all risk-reducing surgeries. PMID: 32199636 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)
Source: Gynecologic Oncology - March 18, 2020 Category: Cancer & Oncology Authors: Rush SK, Swisher EM, Garcia RL, Pennington KP, Agnew KJ, Kilgore MR, Norquist BM Tags: Gynecol Oncol Source Type: research

[Role of the PRED-IdF, a regional network dedicated to patients with hereditary predisposition to digestive cancers].
Abstract Patients with hereditary predisposition to digestive cancer are at high risk of neoplasia and management in expert centers is recommended. The PRED-IdF network was thus created in 2009, with the support of the French National Cancer Institute (INCa), covering Paris and its suburbs, including five teaching hospitals and two oncology-dedicated institutes. The aim of this network is to offer optimized cancer screening programs based on expert recommendations to patients with hereditary predisposition. Any patient with suspicion of hereditary colorectal syndrome can be referred to the PRED-IdF network. The mi...
Source: Annales de Pathologie - March 18, 2020 Category: Pathology Authors: Perrod G, Samaha E, Bats AS, Cellier C Tags: Ann Pathol Source Type: research

Feasibility of endometrial sampling by vaginal tampons in women with Lynch syndrome
Endometrial sampling for the surveillance of women with Lynch syndrome is an invasive and painful procedure. The aim of this study was to evaluate the feasibility of a less invasive procedure of collecting vit... (Source: BMC Women's Health)
Source: BMC Women's Health - March 17, 2020 Category: OBGYN Authors: Jorien M. Woolderink, Geertruida H. De Bock, Bettien M. van Hemel, Erwin Geuken, Harry Hollema, Naomi Werner and Marian J. Mourits Tags: Research article Source Type: research

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care
AbstractThe aims of the Prospective Lynch Syndrome Database (PLSD) are to provide empirical prospectively observed data on the incidences of cancer in different organs, survival following cancer and the effects of interventions in carriers of pathogenic variants of the mismatch repair genes (path_MMR) categorized by age, gene and gender. Although PLSD is assumption-free, as with any study the ascertainment procedures used to identify the study cohort will introduce selection biases which have to be declared and considered in detail in order to provide robust and valid results. This paper provides a commentary on the method...
Source: Hereditary Cancer in Clinical Practice - March 14, 2020 Category: Cancer & Oncology Source Type: research

[The pathology of hereditary ovarian tumors].
Abstract About 23% of adnexal tumors are related to a hereditary syndrome, most often hereditary breast and ovarian cancer syndrome or Lynch syndrome, responsible of epithelial tumors. However, the pathologist should be aware of rare hereditary syndromes responsible of non-epithelial ovarian tumors. Ovarian tumors associated with germline mutation of BRCA genes are essentially high-grade serous carcinomas of tubal origin, while those seen in Lynch syndrome are most often endometrioid or clear cell carcinomas. Sex-cord tumors associated with a familial predisposition are Sertoli-Leydig cell tumors in DICER syndrome...
Source: Annales de Pathologie - March 13, 2020 Category: Pathology Authors: Pesce F, Devouassoux-Shisheboran M Tags: Ann Pathol Source Type: research

Clinicopathological features and oncological outcomes of patients with young-onset rectal cancer.
Abstract BACKGROUND: The incidence of rectal cancer among adults aged less than 50 years is rising. Survival data are limited and conflicting, and the oncological benefit of standard neoadjuvant and adjuvant therapies is unclear. METHODS: Disease-specific outcomes of patients diagnosed with rectal cancer undergoing surgical resection with curative intent between 2006 and 2016 were analysed. RESULTS: A total of 797 patients with rectal cancer were identified, of whom 685 had surgery with curative intent. Seventy patients were younger than 50 years and 615 were aged 50 years or more. C...
Source: The British Journal of Surgery - March 9, 2020 Category: Surgery Authors: Zaborowski AM, Murphy B, Creavin B, Rogers AC, Kennelly R, Hanly A, Martin ST, O'Connell PR, Sheahan K, Winter DC Tags: Br J Surg Source Type: research

Cancers, Vol. 12, Pages 621: High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on TP53
ra Maria Claudia Nogueira Zerbini Francisco Tibor Denes Ana Claudia Latronico Berenice Bilharinho Mendonca Madson Queiroz Almeida Antonio Marcondes Lerario Ibere Cauduro Soares Maria Candida Barisson Villares Fragoso Adrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatri...
Source: Cancers - March 7, 2020 Category: Cancer & Oncology Authors: Vania Balderrama Brondani Luciana Montenegro Amanda Meneses Ferreira Lacombe Breno Marchiori Magalh ães Mirian Yumie Nishi Mariana Ferreira de Assis Funari Amanda de Moraes Narcizo Lais Cavalca Cardoso Sheila Aparecida Coelho Siqueira Maria Claudia Nogue Tags: Article Source Type: research

Primary malignant pericardial tumour in Lynch syndrome
This case represents the first report of malignant primary cardiac tumour in a patient with Lynch Syndrome associated with MSH2 pathogenic variant. (Source: BMC Cancer)
Source: BMC Cancer - March 6, 2020 Category: Cancer & Oncology Authors: Pasquale Paolisso, Giulia Saturi, Alberto Fo à, Maristella Saponara, Margherita Nannini, Maria Abbondanza Pantaleo, Ornella Leone, Daniela Turchetti, Daniele Calistri, Carlo Savini, Davide Pacini, Carmine Pizzi and Nazzareno Galiè Tags: Case report Source Type: research

Mismatch Repair Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy.
PB, Shia J, Schultz N, Garcia-Aguilar J, Diaz LA, Goodman K, Saltz LB, Weiser MR, Smith JJ, Stadler ZK Abstract PURPOSE: Evaluate response of mismatch repair deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: dMMR rectal tumors at Memorial Sloan Kettering were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty dMMR rectal cancer patients were identified by immunohistochemistry and/or microsatellite instability analysis, with initial treatment response compared to a matched pMMR rectal cancer cohort. Germline and somatic mutation analyses were evaluated....
Source: Clinical Cancer Research - March 6, 2020 Category: Cancer & Oncology Authors: Cercek A, Dos Santos Fernandes G, Roxburgh CS, Ganesh K, Ng S, Sanchez-Vega F, Yaeger R, Segal NH, Reidy-Lagunes DL, Varghese AM, Markowitz A, Wu C, Szeglin B, Sauvé CG, Salo-Mullen E, Tran C, Patel Z, Krishnan A, Tkachuk K, Nash GM, Guillem J, Paty PB, Tags: Clin Cancer Res Source Type: research

[Hereditary gastric cancer: Challenges for the pathologist in 2020].
Abstract Gastric cancer is the third most common cancer worldwide. The majority of gastric cancers are sporadic but familial clustering is seen in more than 10% of cases. This manuscript is divided into two parts. The first part is dedicated to the non-syndromic hereditary gastric cancer, particularly the hereditary diffuse gastric cancer (HDGC) and other gastric polyposes including the recently described GAPPS (Gastric adenocarcinoma and proximal polyposis of the stomach). The second part concerns the syndromic gastric cancer, namely the HNPCC syndrome (Hereditary Non Polyposis Colorectal Cancer) occurring as par...
Source: Annales de Pathologie - March 5, 2020 Category: Pathology Authors: Renaud F, Svrcek M Tags: Ann Pathol Source Type: research

The Provision of Genetic Testing and Related Services in Quebec, Canada
ConclusionsIntegration between genetics and the overall healthcare system in Quebec is in an early phase. Current models of genetic services require good level of genetic knowledge by all medical specialists, collaboration among different healthcare personnel, and work redistribution. The proper implementation of genomics into healthcare can be achieved through education and training, proper regulatory oversight, genomic policies, and public awareness. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - March 4, 2020 Category: Genetics & Stem Cells Source Type: research

Coexistent Dedifferentiated Endometrioid Carcinoma of the Uterus and Adenocarcinoma of the Bladder in Lynch Syndrome: Case Report and Review of the Literature
We present a 47-year-old woman with an MLH1 gene mutation (G133X 397G>T) who presented with menorrhagia. Eleven family members have this mutation, 6 with carcinoma: 5 colorectal and 1 with a gynecologic primary of unknown type. Colonoscopy and endoscopy were unremarkable. Positron emission and computed tomography revealed a 3 cm anterior dome bladder mass without additional extrauterine disease or uterine connection. She underwent partial cystectomy, laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. The uterus demonstrated a dedifferentiated endometrioid adenocarcinoma, immunohistochemical...
Source: Applied Immunohistochemistry and Molecular Morphology - March 1, 2020 Category: Chemistry Tags: Online Articles: Case Reports Source Type: research

Colorectal Cancer Screening Practices Among Texas Nurse Practitioners and Physician Assistants
The purpose of this study was two-fold: (1) To describe and compare Texas Nurse Practitioners' and Physician Assistants' knowledge and use of current screening guidelines for individuals at varying risk for colorectal cancer and (2) to compare their recommendations for referral for genetic counseling for persons at increased risk for colorectal or endometrial cancer. The study used a descriptive correlational comparative design. A self-administered web-based survey was sent to the members of the Texas Nurse Practitioner Association and the Texas Academy of Physician Assistants. The questionnaire consisted of 44 items categ...
Source: Gastroenterology Nursing - March 1, 2020 Category: Nursing Tags: Features Source Type: research

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria.
CONCLUSIONS: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.. PMID: 32102509 [PubMed - in process] (Source: Asian Pacific Journal of Cancer Prevention)
Source: Asian Pacific Journal of Cancer Prevention - February 28, 2020 Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research

A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family
(Source: Cancer Management and Research)
Source: Cancer Management and Research - February 27, 2020 Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research

Do the risks of Lynch syndrome-related cancers depend on the parent of origin of the mutation?
AbstractIndividuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR  = 1 corresponds to no POE and HR > ...
Source: Familial Cancer - February 27, 2020 Category: Cancer & Oncology Source Type: research

Functional Characterization of a Missense Variant of MLH1 Identified in Lynch Syndrome Pedigree.
In conclusion, our findings widen the genotypic spectrum of MLH1 mutations responsible for LS. This study increases the phenotypic spectrum of LS which will certainly help the clinicians in diagnosing LS in multigeneration families. This study also puts emphasis on the importance of genetic counselling for the benefit of asymptomatic carriers of MMR gene variants who are at higher risk of LS. PMID: 32076465 [PubMed - in process] (Source: Disease Markers)
Source: Disease Markers - February 23, 2020 Category: Laboratory Medicine Tags: Dis Markers Source Type: research

Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer
AbstractThe advent of gene panel testing is challenging the previous practice of using clinically defined cancer family  syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have a pplied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1,MSH2,MSH6 andPMS2) to an Australian population-based case –control-family study of breast cancer. Altogether, eig...
Source: Familial Cancer - February 14, 2020 Category: Cancer & Oncology Source Type: research

Muir-Torre Syndrome With a Frame-shift Mutation in the MSH2 Gene: A Rare Case Report and Literature Review
Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syn...
Source: International Journal of Gynecological Pathology - February 12, 2020 Category: Pathology Tags: Pathology of the Corpus: Case Reports Source Type: research

The implications of BRCA loss of heterozygosity (LOH) and deficient mismatch repair gene (dMMR) expression in the breast cancer of a patient with both inherited breast and ovarian cancer syndrome (BRCA2) and Lynch syndrome (MLH1)
ConclusionThe patient presented represents the first reported case where both next generation sequencing (NGS) forBRCA LOH and MMR IHC testing of her breast cancer were performed and underscores the importance of using NGS including the reported mutational allelic frequency (MAF) and IHC use to predict the likely responsiveness to the recently approved PARP inhibitors and checkpoint inhibitor therapies (Robson et al in N Engl J Med 377:523 –533, 2017, Lemery et al in 377(15):1409–1412,, 2017), key because the gatekeeper transforming event for tumors related to inherited cance...
Source: Breast Cancer Research and Treatment - February 10, 2020 Category: Cancer & Oncology Source Type: research

[Clinical Cancer Genetics: A guide for the pathologist].
io PR Abstract It is paramount to identify patients whose cancer is associated with genetic susceptibility to the disease, since their long-term management depends on it. Anatomical and molecular pathologists play a key role in the process. Indeed, their diagnosis supports or even sometimes warrants germline genetic testing. For example, a colorectal cancer with mismatch repair protein expression loss suggests Lynch syndrome, while a rare type of renal cell carcinoma with fumarate hydrate expression loss is highly evocative of hereditary leiomyomatosis and renal cell carcinoma syndrome. Similarly, the presence of ...
Source: Annales de Pathologie - February 8, 2020 Category: Pathology Authors: Basset N, Desseignés C, Boucher C, Coulet F, Benusiglio PR Tags: Ann Pathol Source Type: research

Natural language processing for the accurate identification of colorectal cancer mismatch repair status in Lynch syndrome screening
(Source: Clinical Gastroenterology and Hepatology)
Source: Clinical Gastroenterology and Hepatology - February 6, 2020 Category: Gastroenterology Authors: Dan Li, Natalia Udaltsova, Evan Layefsky, Cecilia Doan, Douglas A. Corley Source Type: research

MSH6 gene pathogenic variant identified in familial pancreatic cancer in the absence of colon cancer
Conclusions Lynch syndrome should be suspected in families with familial pancreatic cancer, even in the absence of colon cancers. Specifically, our observation supports the association between the MSH6 c.2194C>T pathogenic variant and extracolonic tumours and it suggests that MSH6 pathogenic variants are associated with familial pancreatic cancer more frequently than assumed. (Source: European Journal of Gastroenterology and Hepatology)
Source: European Journal of Gastroenterology and Hepatology - February 4, 2020 Category: Gastroenterology Tags: Original Articles: Gastroenterology Source Type: research

Exam 2: Clinical Factors Associated With Gastric Cancer in Individuals With Lynch Syndrome
(Source: Clinical Gastroenterology and Hepatology)
Source: Clinical Gastroenterology and Hepatology - February 1, 2020 Category: Gastroenterology Tags: Continuing Medical Education (CME) Activity Source Type: research

Microsatellite instability detection using a large next-generation sequencing cancer panel across diverse tumour types.
CONCLUSION: This study highlights the utility of this approach, which should be applicable to laboratories performing similar testing. PMID: 31530574 [PubMed - indexed for MEDLINE] (Source: Clinical Colorectal Cancer)
Source: Clinical Colorectal Cancer - February 1, 2020 Category: Cancer & Oncology Authors: Pang J, Gindin T, Mansukhani M, Fernandes H, Hsiao S Tags: J Clin Pathol Source Type: research

Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics
AbstractRoutine diagnostics for colorectal cancer patients suspected of having Lynch-Syndrome (LS) currently uses Next-Generation-Sequencing (NGS) of targeted regions within the DNA mismatch repair (MMR) genes. This analysis can reliably detect nucleotide alterations and copy-number variations (CNVs); however, CNV-neutral rearrangements comprising gene inversions or large intronic insertions remain undetected because their breakpoints are usually not covered. As several founder mutations exist for LS, we established PCR-based screening methods for five known rearrangements inMLH1,MSH2, orPMS2, and investigated their preval...
Source: Familial Cancer - January 30, 2020 Category: Cancer & Oncology Source Type: research

Risk of Metachronous Colorectal Neoplasm After a Segmental Colectomy in Lynch Syndrome Patients According to Mismatch Repair Gene Status
Because of increased risk of metachronous colorectal cancer (CRC), all Lynch Syndrome (LS) patients are offered a total colectomy. However, since metachronous CRC rate by MMR gene is uncertain, and total colectomy negatively impacts quality of life, it remains unclear whether segmental resection is indicated for lower penetrance MMR genes. We evaluated metachronous CRC incidence according to MMR gene in LS patients who underwent a segmental colectomy. (Source: Journal of the American College of Surgeons)
Source: Journal of the American College of Surgeons - January 30, 2020 Category: Surgery Authors: Felipe F. Quezada-Diaz, Irbaz Hameed, Alexa von Mueffling, Erin E. Salo-Mullen, John D. Catalano, J Joshua Smith, Martin R. Weiser, Julio Garcia-Aguilar, Zsofia K. Stadler, Jose G. Guillem Tags: Southern Surgical Association Article Source Type: research

Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS): a descriptive study
AbstractTo prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers ’ attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent ...
Source: Familial Cancer - January 29, 2020 Category: Cancer & Oncology Source Type: research

Detection of DNA mismatch repair deficient crypts in random colonoscopic biopsies identifies Lynch syndrome patients
AbstractThe hallmark of Lynch syndrome (LS)-associated neoplasia is DNA mismatch repair protein (MMR) deficiency. Recent studies have demonstrated that histologically normal colonic crypts in patients with LS can exhibit deficient MMR expression. The aim of this study was to determine the feasibility of detecting MMR deficient crypts in random colonoscopic biopsies of normal mucosa in patients with and without LS. Forty-nine patients, including 33 with LS, 12 without LS, and 4 with germline MMR gene variants of uncertain significance (VUS), were prospectively and blindly evaluated by immunohistochemistry for MMR deficient ...
Source: Familial Cancer - January 29, 2020 Category: Cancer & Oncology Source Type: research

Preventing Ovarian Cancer in High-risk Women: One Surgery at a Time
Eleven genes have been identified that increase the lifetime risk of developing ovarian cancer. The cumulative cancer risk of ovarian cancer varies with the mutation type and age. Ovarian cancer risk management options include surgical risk reduction with salpingo-oophorectomy and a newer step-wise approach with interval salpingectomy and delayed oophorectomy. Women should be counseled on the pros and cons of hysterectomy in the setting of reducing the risk of other cancers; eliminating the risk of endometrial cancer in Lynch Syndrome, potential risk of serous/serous-like endometrial cancer in BRCA1 carriers, and eliminati...
Source: Clinical Obstetrics and Gynecology - January 25, 2020 Category: OBGYN Tags: New and Novel Treatments for Gynecologic Cancer Source Type: research

Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome
Genetics in Medicine, Published online: 22 January 2020; doi:10.1038/s41436-019-0736-2Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome (Source: Genetics in Medicine)
Source: Genetics in Medicine - January 22, 2020 Category: Genetics & Stem Cells Authors: Mark Drost Yvonne Tiersma Dylan Glubb Scott Kathe Sandrine van Hees Fabienne Call éja Jos é B. M. Zonneveld Kenneth M. Boucher Renuka P. E. Ramlal Bryony A. Thompson Lene Juel Rasmussen Marc S. Greenblatt Andrea Lee Amanda B. Spurdle Sean V. Tavtigian N Source Type: research

An update on the CNS manifestations of brain tumor polyposis syndromes
AbstractCancer predisposition syndromes are associated with an increased risk of developing primary malignancies. Here we discuss those which are associated with an increased risk of tumors of the central nervous system (CNS) and gastrointestinal (GI) tract. These can be grouped into those in which the CNS tumors predominate versus those in which the GI cancers predominate. The former include constitutional mismatch repair deficiency (CMMRD) syndrome, Li –Fraumeni syndrome (LFS), and Cowden syndrome (CS) while the latter include familial adenomatosis polyposis 1 (FAP1), Lynch syndrome and polymerase proofreading-asso...
Source: Acta Neuropathologica - January 22, 2020 Category: Neurology Source Type: research

Analysis of 108 patients with endometrial carcinoma using the PROMISE classification and additional genetic analyses for MMR-D.
CONCLUSION: The ProMisE classification proved to be an efficient and easily implementable system. Future research should elucidate the precise biological and prognostic meaning of the cases with multiple molecular markers. PMID: 31980219 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)
Source: Gynecologic Oncology - January 21, 2020 Category: Cancer & Oncology Authors: Timmerman S, Van Rompuy AS, Van Gorp T, Vanden Bempt I, Brems H, Van Nieuwenhuysen E, Han SN, Neven P, Victoor J, Laenen A, Vergote I Tags: Gynecol Oncol Source Type: research

Genetic Testing for Epithelial Ovarian Cancer
Publication date: Available online 16 January 2020Source: Best Practice & Research Clinical Obstetrics & GynaecologyAuthor(s): Noa Amin, Narda Chaabouni, Angela GeorgeAbstractAs the treatment of epithelial ovarian cancer moves further into personalised medicine, the importance of determining the presence or absence of inherited mutations in cancer susceptibility genes has grown. It is now becoming routine to test for germline mutations in the BRCA1 and BRCA2 genes, which are responsible for a significant proportion of hereditary epithelial ovarian cancer and are established predictive biomarkers of potential benefi...
Source: Best Practice and Research Clinical Obstetrics and Gynaecology - January 18, 2020 Category: OBGYN Source Type: research

Utility of the immunohistochemical analysis of DNA mismatch-repair proteins in endometrial hyperplasia.
In conclusion, only two endometrial hyperplasias displayed an altered pattern of MMR expression. Our results suggest the limited utility of the immunohistochemical analysis of MMR protein in the early detection of Lynch syndrome in Tunisian patients diagnosed with endometrial hyperplasias. Multicenter studies with larger sample size are needed to more explore these findings. PMID: 31955910 [PubMed - as supplied by publisher] (Source: Acta Histochemica)
Source: Acta Histochemica - January 16, 2020 Category: Biochemistry Authors: Missaoui N, Boukhari N, Limam S, Hmissa S, Mokni M Tags: Acta Histochem Source Type: research

Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
ConclusionIdentification of families with Lynch syndrome, while challenging because of variable phenotypes at diagnosis, is feasible with available molecular biological technologies and crucial to reduce mortality caused by this syndrome. (Source: Journal of Gastrointestinal Cancer)
Source: Journal of Gastrointestinal Cancer - January 14, 2020 Category: Cancer & Oncology Source Type: research

Frequent loss of mutation-specific mismatch repair protein expression in nonneoplastic endometrium of Lynch syndrome patients
Modern Pathology, Published online: 13 January 2020; doi:10.1038/s41379-020-0455-xFrequent loss of mutation-specific mismatch repair protein expression in nonneoplastic endometrium of Lynch syndrome patients (Source: Modern Pathology)
Source: Modern Pathology - January 13, 2020 Category: Pathology Authors: Serena Wong Pei Hui Natalia Buza Source Type: research

Distinct Immunological Landscapes Characterize Inherited and Sporadic Mismatch Repair Deficient Endometrial Cancer
Around 30% of endometrial cancers (EC) are mismatch repair (MMR) deficient, mostly as a consequence of mutations acquired during tumorigenesis, but a significant minority is caused by Lynch syndrome (LS). This inherited cancer predisposition syndrome primes an anti-cancer immune response, even in healthy carriers. We sought to explore the intra-tumoral immunological differences between genetically confirmed LS-associated MMR-deficient (MMRd), sporadic MMR-deficient, and MMR-proficient (MMRp) EC. Endometrial tumors from women with known LS were identified (n = 25). Comparator tumors were recruited prospectively and underwen...
Source: Frontiers in Immunology - January 9, 2020 Category: Allergy & Immunology Source Type: research

Extent of Pedigree Required to Screen for and Diagnose Hereditary Nonpolyposis Colorectal Cancer: Comparison of Simplified and Extended Pedigrees
CONCLUSIONS: A simplified pedigree is acceptable for selecting candidates to screen for hereditary colorectal cancer, whereas an extended pedigree is still required for a more precise diagnosis of Lynch syndrome, especially in younger patients. See Video Abstract at EXTENSIÓN DE PEDIGREE REQUERIDO EN LA DETECCIÓN Y DIAGNÓSTICO DE CÁNCER COLORRECTAL HEREDITARIO SIN POLIPOSIS: COMPARACIÓN DE LOS PEDIGREES SIMPLIFICADO Y EL EXTENDIDO ANTECEDENTES: La obtención de un Pedigree exacto es el primer paso para reconocer un paciente con cáncer color...
Source: Diseases of the Colon and Rectum - January 8, 2020 Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research

Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome
Lynch syndrome is caused by alterations in a specific group of genes. Patients with different types of genetic alterations develop adenomas and CRC at different rates, and tumors have specific genetic features. (Source: Gastroenterology)
Source: Gastroenterology - January 8, 2020 Category: Gastroenterology Authors: Christoph Engel, Aysel Ahadova, Toni Sepp älä, Stefan Aretz, Marloes Bigirwamungu-Bargeman, Hendrik Bläker, Karolin Bucksch, Reinhard Büttner, Wouter de Vos tot Nederveen Cappel, Volker Endris, Elke Holinski-Feder, Stefanie Holzapfel, Robert Hüneburg Source Type: research