Clinical Implication of CDH1 Mutations in Genetic Testing for Diffuse Gastric Cancer Patients.

INTRODUCTION: The objective of this study was to reclassify published germline CDH1 variants identified in gastric cancer (GC) in accordance with the latest ClinVar definition and to correlate their pathogenicity with the established international clinical criteria for genetic testing. METHODS: The relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations in accord with PRISMA guidelines. The collected variants were classified according to the latest ClinVar definition into the following classes: benign (B), likely benign (LB), pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS). The McNemar test was used to compare the adequacy of current versus previous International GC Linkage Consortium (IGCLC) criteria. RESULTS: We reclassified a total of 247 CDH1 variants, and we identified that about 70% of B/LB variant carriers were not fulfilling the defined clinical criteria. Instead, all P/LP variants (100%) were associated with the hereditary diffuse gastric cancer (HDGC) phenotype fulfilling the 2020 ILGCC criteria, with a significant improvement (p = 0.025) compared to previous version. CONCLUSIONS: We conclude that germline CDH1 genetic testing is indicated only in families meeting the clinical criteria for the HDGC syndrome. This observation suggests that clinical phenotypes that do not clearly fulfill these criteria should not be considered for CDH1 genetic testing.

Advances in breast cancer risk modeling: integrating clinics, imaging, pathology and artificial intelligence for personalized risk assessment.

Breast cancer risk models represent the likelihood of developing breast cancer based on risk factors. They enable personalized interventions to improve screening programs. Radiologists identify mammographic density as a significant risk factor and test new imaging techniques. Pathologists provide data for risk assessment. Clinicians conduct individual risk assessments and adopt prevention strategies for high-risk subjects. Tumor genetic testing guides personalized screening and treatment decisions. Artificial intelligence in mammography integrates imaging, clinical, genetic and pathological data to develop risk models. Emerging imaging technologies, genetic testing and molecular profiling improve risk model accuracy. The complexity of the disease, limited data availability and model inputs are discussed. A multidisciplinary approach is essential for earlier detection and improved outcomes.

Germline CDH1 variants in hereditary diffuse gastric cancer syndrome with focus on younger women.

PURPOSE: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome. METHODS: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant. RESULTS: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021). CONCLUSIONS: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC.

Do Preoperative Transfusions Impact Prognosis in Moderate to Severe Anaemic Surgical Patients with Colon Cancer?

(1) Background: Anaemia is a common finding in patients with colon cancer and is commonly corrected by blood transfusion prior to surgery. However, the prognostic role of perioperative transfusions is still debated. The aim of the present study was to investigate the role of preoperative anaemia and preoperative blood transfusion in influencing the prognosis in colon cancer. (2) Patients and Methods: Patients undergoing elective surgery for colon cancer at a tertiary referral university hospital between January 2010 and December 2018 were included in a retrospective review of a prospectively collected database. Univariate and regression analyses were performed to identify the prognostic role of preoperative anaemia and preoperative transfusions in this homogeneous cohort of patients. (3) Results: A total of 780 patients were included in the final analysis. The estimated five-year overall survival rate was significantly worse in the anaemic group (83.8% in non-anaemic patients, 60.6% in mild anaemic patients, 61.3% in moderate anaemic patients and 58.4% in severe anaemic patients; log-rank < 0.001 vs. non-anaemic patients). Anaemic status was found to be an independent adverse prognostic factor (hazard ratio (HR): 1.46; 95% confidence interval (CI): 1.02-2.07) during multivariate analysis. Among moderate to severe anaemic patients, no significant association was found between preoperative transfusions and the risk of mortality or recurrence. (4) Conclusions: Preoperative anaemia, regardless of its severity, and not preoperative blood transfusion, was independently associated with a worse prognosis after surgery in patients with colonic cancer.