• colorectal cancer
• endometrial cancer
• microsatellite instability
• mismatch repair proteins

• Humans
• Female
• Middle Aged
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• DNA Mismatch Repair
• Male
• Aged
• Mismatch Repair Endonuclease PMS2
• Endometrial Neoplasms/diagnosis
• Endometrial Neoplasms/genetics
• Adult
• DNA-Binding Proteins
• Biomarkers, Tumor
• Immunohistochemistry/methods
• Neoplastic Syndromes, Hereditary/diagnosis
• Aged, 80 and over
• MutL Protein Homolog 1/genetics
• Brain Neoplasms

• Colorectal cancer
• Hereditary colorectal cancer
• Lynch syndrome
• Universal tumor screening

• Humans
• Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis
• Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
• Colorectal Neoplasms, Hereditary Nonpolyposis/surgery
• Early Detection of Cancer/methods
• Genetic Testing/methods
• Biopsy
• Genetic Counseling
• DNA Mismatch Repair/genetics
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/surgery
• MutL Protein Homolog 1/genetics

Lynch Syndrome (LS) represents the hereditary condition that is most frequently associated with endometrial cancer (EC). The aim of this study is to assess the presence of Lynch Syndrome (LS) in young women with mismatch repair (MMR)-deficient atypical endometrial hyperplasia (AEH) and non-myoinvasive FIGO G1 endometrioid EC and its possible impact on the outcome of conservative treatment.

Six MMR-deficient cases identified from a previous cohort of 69 conservatively treated patients were selected to be screened for germline mutations in MMR genes. In each patient, the outcomes of conservative treatment for AEH and EEC, including response, relapse, progression, and pregnancy, were assessed.

Five out of 6 patients underwent genetic test for LS. Three out of these 5 patients showed a positive genetic test. Patient 1 showed the c.942 + 2 T>A heterozygous variant of MSH2 mutation; after 12 months of complete response, she had relapse and progression of disease. Patient 4 showed the c.2459-1G>C variant of MSH2 mutation; after complete response, she failed to achieve pregnancy; she had relapse after 24 months and underwent hysterectomy. Patient 6 showed the c.803 + 1 heterozygous variant of PMS2 mutation; she had relapse of disease after 18 months from the first complete response and then underwent hysterectomy.

In this series, 3 out of 6 women with MMR-deficiency had LS. None of the patients achieved pregnancy, and those who responded to treatment had subsequent relapse of disease. Patients undergoing fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer should perform MMR immunohistochemical analysis in order to screen LS.

• Quality of Health Economic Studies
• colorectal cancer
• cost–effectiveness analysis
• genomics
• health economics
• molecular diagnostics
• systematic review

Few studies on the clinicopathological features and prognosis of DNA mismatch repair deficiency (dMMR) gastric cancer (GC) have been reported, and no clear conclusions have been drawn about the factors affecting the prognosis of dMMR GC. The aim of this study was to explore the clinicopathological characteristics and prognoses of dMMR GC patients.

From May 2011 to November 2020, GC patients who underwent surgery with dMMR confirmed by immunohistochemistry (IHC) at the Affiliated Cancer Hospital of Shanxi Medical University were selected. The patients' clinical and pathological data were collected. The recurrence-free survival (RFS) and overall survival (OS) rates of the patients were determined through follow-up. SPSS 26.0 was used to analyze the patients' clinicopathological features and prognoses.

A total of 162 dMMR GC patients met the inclusion criteria, and the median age was 63.5 years (32–89 years). dMMR GC was more common in males (65% vs. 35%), and most of the cases were stage II (the prevalence of stage I was 22%, that of stage II was 43%, that of stage III was 30%, and that of stage IV was 5%). Most of the lesions were located in the antrum (49%), followed by the cardia (25%). PMS2 and MLH1 (57%) deficiency was most common. Kaplan–Meier analysis showed that factors related to OS were family history (P = 0.048), number of lymph node (LN) metastases (P < 0.001), vascular tumor thrombus (P < 0.001), HER2 expression status (P = 0.025), and clinical stage (P < 0.001). The factors related to RFS included vascular tumor thrombus (P < 0.001), number of LN metastases (P < 0.001), and clinical stage (P < 0.001).

In this study, dMMR GC was more common in men, and the median age was 63.5 years. Most of the lesions were in the antrum and showed the combined deletion of MLH1 and PMS2. dMMR GC patients tended to be early stage, and the prognosis of those with early-stage GC was better. dMMR GC patients with vascular tumor thrombus or >6 LN metastases had a high recurrence rate and poor survival outcome.

• Adenocarcinoma
• Cost-effectiveness
• DNA mismatch repair
• Immunochemistry
• Microsatellite instability
• Monoclonal antibody

Lynch syndrome (LS) is the commonest inherited cancer syndrome caused by pathogenic variants of germline DNA mismatch repair (g.MMR) genes. Genome‐wide sequencing is now increasingly applied for tumor characterization, but not for g.MMR. The aim of this study was to evaluate the incidence and pathogenicity of g.MMR variants in Japanese cancer patients.

Four g.MMR genes (MLH1, MSH2, MSH6, and PMS2) were analyzed by next generation sequencing in 1058 cancer patients (614 male, 444 female; mean age 65.6 years) without past diagnosis of LS. The g.MMR variant pathogenicity was classified based on the ClinVar 2015 database. Tumor MMR immunohistochemistry, microsatellite instability (MSI), and BRAF sequencing were also investigated in specific cases.

Overall, 46 g.MMR variants were detected in 167 (15.8%) patients, 17 likely benign variants in 119 patients, 24 variants of uncertain significance (VUSs) in 68 patients, two likely pathogenic variants in two patients, and three pathogenic variants in three (0.3%) patients. The three pathogenic variants included two colorectal cancers with MLH1 loss and high MSI and one endometrial cancer with MSH6 loss and microsatellite stability. Two likely pathogenic variants were shifted to VUSs by ClinVar (2018). One colon cancer with a likely benign variant demonstrated MLH1 loss and BRAF mutation, but other nonpathogenic variants showed sustained MMR and microsatellite stability.

Universal sequencing of g.MMR genes demonstrated sundry benign variants, but only a small proportion of cancer patients had pathogenic variants. Pathogenicity evaluation using the ClinVar database agreed with MSI, MMR immunohistochemistry, and BRAF sequencing.

• Lynch syndrome
• exome sequencing
• mismatch repair gene
• next generation sequencing
• pathogenicity
• variant of uncertain significance

• Lynch syndrome
• endometrial cancer
• gynecologic oncology
• immunohistochemistry
• microsatellite instability
• mutL homolog 1 (MLH1) methylation

The study objective was to assess US physicians’ Mismatch Repair/Microsatellite Instability (MMR/MSI) testing practices for metastatic colorectal cancer (mCRC) patients. A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC patients in the US. Eligible physicians were US-based with at least 5 years of experience treating CRC patients, had at least one mCRC patient in their routine care in the past 6 months, and had ordered at least one MMR/MSI test for CRC in the past 6 months. Descriptive and logistic regression analyses were performed. Awareness of specific MMR/MSI testing guidelines was high (n = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of National Comprehensive Cancer Network (NCCN) guidelines. Universal testing for all CRC patients was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively order the test for some CRC patients. Key barriers for testing included insufficient tissue sample (48.3%, 73/151), patient declined to have the test done (35.8%, 54/151) and insurance cost concerns for patients (31.1%, 47/151), while 27.2% (41/151) reported no barriers. The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal.

• colorectal cancer
• mismatch repair/microsatellite instability testing
• survey

• Lynch syndrome
• colorectal cancer
• ethnic diversity
• universal screening

• Lynch syndrome
• MLH1
• MSH2
• MSH6
• PMS2
• immunohistochemistry
• mutation screening
• universal testing

• Family communication
• Lynch syndrome
• Patient education

• Adult
• Aged
• Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis
• Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
• Communication
• Communication Barriers
• Family/psychology
• Female
• Genetic Testing/methods
• Health Knowledge, Attitudes, Practice
• Humans
• Information Dissemination
• Interviews as Topic
• Male
• Middle Aged
• Patient Education as Topic/methods

• K07 CA196985 NCI NIH HHS
• P30 CA042014 NCI NIH HHS
• UL1 RR025764 NCRR NIH HHS
• UL1 TR002538 NCATS NIH HHS

• Colorectal cancer
• Genetic testing
• HBOC
• Lynch syndrome
• Pancreatic cancer

• Adult
• Aged
• Breast Neoplasms/genetics
• Colorectal Neoplasms/genetics
• Female
• Genetic Predisposition to Disease
• Genetic Testing
• Humans
• Male
• Middle Aged
• Ovarian Neoplasms/genetics
• Pancreatic Neoplasms/genetics

• UL1 TR002538 NCATS NIH HHS
• R01 CA164138 NCI NIH HHS
• R01CA164138 NCI NIH HHS
• T32 HG008962 NHGRI NIH HHS
• P30CA042014 NCI NIH HHS
• 1T32HG008962-01 NIH HHS
• P30 CA042014 NCI NIH HHS
• National Cancer Institute
• Utah Genome Project
• Canadian Institutes of Health Research
• Huntsman Cancer Foundation
• National Institutes of Health
• Genome Canada

Due to its epidemiological relevance, several studies have been performed to assess the cost-effectiveness of diagnostic tests and treatments in colorectal cancer (CRC) patients.

We reviewed economic evaluations on diagnosis of inherited CRC-syndromes and genetic tests for the detection of mutations associated with response to therapeutics.

A systematic literature review was performed by searching the main literature databases for relevant papers on the field, published in the last 5 years.

20 studies were included in the final analysis: 14 investigating the cost-effectiveness of hereditary-CRC screening; 5 evaluating the cost-effectiveness of KRAS mutation assessment before treatment; and 1 study analysing the cost-effectiveness of genetic tests for early-stage CRC patients prognosis. Overall, we found that: (a) screening strategies among CRC patients were more effective than no screening; (b) all the evaluated interventions were cost-saving for certain willingness-to-pay (WTP) threshold; and (c) all new CRC patients diagnosed at age 70 or below should be screened. Regarding patients treatment, we found that KRAS testing is economically sustainable only if anticipated in patients with non-metastatic CRC (mCRC), while becoming unsustainable, due to an incremental cost-effectiveness ratio (ICER) beyond the levels of WTP-threshold, in all others evaluated scenarios.

The poor evidence in the field, combined to the number of assumptions done to perform the models, lead us to a high level of uncertainty on the cost-effectiveness of genetic evaluations in CRC, suggesting that major research is required in order to assess the best combination among detection tests, type of genetic test screening and targeted-therapy.

The online version of this article (10.1186/s12962-018-0085-z) contains supplementary material, which is available to authorized users.

• CRC
• Colorectal cancer
• Cost-effectiveness analysis
• Economic evaluation
• Personalized medicine

• Colorectal carcinoma
• Cost analysis
• Lynch syndrome
• System dynamics
• Universal screening

• Colorectal and Endometrial cancers
• DNA mismatch repair gene
• Lynch syndrome
• Microsatellite instability

Varying estimates of the cost-effectiveness of genomic testing applications can reflect differences in study questions, settings, methods and assumptions. This review compares recently published cost-effectiveness analyses of testing strategies for Lynch Syndrome (LS) in tumors from patients newly diagnosed with colorectal cancer (CRC) for either all adult patients or patients up to age 70 along with cascade testing of relatives of probands. Seven studies published from 2010 through 2015 were identified and summarized. Five studies analyzed the universal offer of testing to adult patients with CRC and two others analyzed testing patients up to age 70; all except one reported incremental cost-effectiveness ratios (ICERs) < $ 100,000 per life-year or quality-adjusted life-year gained. Three studies found lower ICERs for selective testing strategies using family history-based predictive models compared with universal testing. However, those calculations were based on estimates of sensitivity of predictive models derived from research studies, and it is unclear how sensitive such models are in routine clinical practice. Key model parameters that are influential in ICER estimates included 1) the number of first-degree relatives tested per proband identified with LS and 2) the cost of gene sequencing. Others include the frequency of intensive colonoscopic surveillance, the cost of colonoscopy, and the inclusion of extracolonic surveillance and prevention options.

• Lynch syndrome
• colorectal cancer
• cost-effectiveness
• genetic testing
• genomics
• health economics
• hereditary cancer

• CC999999 Intramural CDC HHS

• CMMR-D
• Lynch syndrome
• Lynch-like syndrome
• MMR IHC
• Microsatellite instability
• Sporadic MSI cancer