Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome

Abstract

IntroductionSeveral studies evaluated the prevalence of Lynch Syndrome (LS) in young onset colorectal cancer (CRC) patients and the results were extremely variable (5%-20%). Immunohistochemistry (IHC) for MMR proteins and/or MSI analysis are screening tests that are done, either by themselves or in conjunction, on colon cancer tissue to identify individuals at risk for LS. The primary aim of our study was to evaluate the prevalence of LS in a large series of early-onset CRC without family history compared with those with family history. The secondary aim was to assess the diagnostic accuracy of IHC and MSI analysis as pre-screening tools for LS.MethodsEarly-onset CRC patients (≤ 50 years) were prospectively recruited in the study. IHC and MSI analysis were performed in all the patients. Germ-line mutation analysis (GMA) was carried out in all MMR deficient tumors. A logistic regression model was performed to identify clinical features predictive of MSI-H.Results117 early onset CRC cases were categorized in three groups (A, B, C) according with family history of CRC. IHC and MSI analysis showed MMR deficiency in 6/70 patients (8.6%) of group A, 24/40 patients (60%) of group B and none of group C. GMA showed a deleterious mutation in 19 (47.5%) patients of group B. MSI analysis had a diagnostic accuracy of 95.7% (CI 92.1-99.4) and IHC of 83.8% (CI 77.1-90.4). The logistic regression model revealed that by using a combination of the two features “No Amsterdam Criteria” and ”left sided CRC” to exclude MSI-H, accuracy was 89.7% (84.2-95.2).ConclusionsEarly-onset CRC patients, with left sided CRC and without family history are “at very low risk” for Lynch syndrome. The two simple criteria of family history and CRC site could be used as a pre-screening tool to evaluate whether or not patients should undergo tissue molecular screening. In the few cases of suspected LS (right sided CRC and/or Amsterdam Criteria), a reasonable approach could be to perform MSI analysis first and IHC afterwards only in MSI-H patients.

Rising Incidence of Colorectal Cancer Among Young Hispanics in Texas

“…While inherited predisposition should always be considered in young patients with CRC, only a minority of young-onset CRC cases can be attributed to a recognized genetic syndrome, and there are no data to suggest that the frequency of any genetic syndrome associated with young-onset CRC is rising 22–24 . Investigation into potential etiologies underlying the rising incidence of young-onset CRC has therefore shifted towards environmental factors – either a single factor or a combination of factors, with or without concomitant genetic predisposition.…”

Induction of active demethylation and 5hmC formation by 5-azacytidine is TET2 dependent and suggests new treatment strategies against hepatocellular carcinoma

“…Scoring for immunohistochemical staining was performed by SAS and BS. All specimens were evaluated according to the 0–4 grading criteria (based on the percentage of 5hmC positive cells) and 0–3 grading criteria (based on the staining intensity) [ 33 ]. The intensity score was multiplied with percentage of positive cells of three different high power fields for each section.…”

Checkpoint inhibition and melanoma: Considerations in treating the older adult

“…[22] The efficacy of the PD-1 blocking antibodies in older adults with advanced melanoma was also assessed in a number of randomized clinical trials. In CheckMate 066, when compared to dacarbazine, treatment with nivolumab was associated with a HR of 0.44 (0.24 – −0.81) in adults aged 65–75 and a HR of 0.25 (0.10 – −0.61) in adults aged >75 years.…”