Anatomic pathology selected abstracts

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Clinical impact of testing for biomarkers in gastric cancer patients

HER2 was the first biomarker for guided therapy registered for clinical use in gastric cancer. Considering the recent approvals of immune checkpoint blockade in gastro-oesophageal cancers, it is increasingly important to test for mismatch repair deficiency (dMMR), Epstein–Barr virus (EBV), and PD-L1 combined positive score (CPS). The authors conducted a study in which they assessed biomarker testing performed in daily clinical practice and its impact on therapeutic choices, with the intent of proposing a practical approach to assessing biomarkers in gastric cancer patients. The study included patients diagnosed with gastric cancer between 2017 and 2021. Biomarker results were retrieved from patients’ EMR files. PD-L1 CPS was determined retrospectively on dMMR and EBV-positive (EBV+) tumors. Data on genomic sequencing were analyzed separately. Of 363 patients identified, 45 percent had metastatic disease. At least one biomarker was tested in 335 (92 percent) patients. The prevalence of HER2+, dMMR, and EBV+ tumors was 10 percent (32 of 319), seven percent (20 of 294), and one percent (three of 235), respectively. Of the dMMR and EBV+ tumors, 95 percent had a PD-L1 CPS of five or more. Therapeutic strategy was adjusted in 31 of 55 (56 percent) patients and consisted of anti-HER2 therapies and immune checkpoint blockade in clinical trials. Genomic alterations were found in 44 of 60 (73 percent) of the patients. TP53 (73 percent) and PIK3CA (21 percent) were the most common mutations, followed by KRAS (11 percent) and amplification of the KRAS gene (11 percent). The authors concluded that in this real-world cohort, testing for HER2, dMMR, and EBV status affected treatment decisions in 56 percent of patients. Although most dMMR and EBV+ tumors had a PD-L1 CPS of five or more, not all patients with a high probability of treatment response were identified. Based on these results, the authors propose a stepwise diagnostic strategy.

Van der Sluis K, van Sandick JW, van Dieren JM, et al. The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort. Histopathology. 2023;82(6):826–836.

Correspondence: Dr. Liudmila L. Kodach at l.kodach@nki.nl

Fibrosis progression in nonalcoholic fatty liver disease among people with and without diabetes

Data are limited regarding progression of fibrosis in biopsy-proven nonalcoholic fatty liver disease among people with type 2 diabetes mellitus compared with people without the latter disease. The authors conducted a large, multi-center study to assess the time to fibrosis progression and regression in people with and without type 2 diabetes mellitus (T2DM) who had paired liver biopsies. The study included 447 adult participants (64 percent of whom were female) with nonalcoholic fatty liver disease who had paired liver biopsies more than one year apart. A central pathology committee blinded to clinical data systematically assessed liver histology. The primary outcome was the cumulative incidence of a one-stage or greater increase in fibrosis among participants with T2DM compared with participants without T2DM. The mean age of participants was 50.9 years (standard deviation [SD], 11.5 years) and mean body mass index (calculated as weight in kilograms divided by the square of the height in meters) was 34.7 (SD, 6.3). The median time between biopsies was 3.3 years (interquartile range, 1.8–6.1 years). The authors found that participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at four years (24 versus 20 percent), eight years (60 versus 50 percent), and 12 years (93 versus 76 percent) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95 percent confidence interval, 1.17–2.43; P = .005). The cumulative incidence of fibrosis regression by one stage or more was similar in participants with and without T2DM (P = .24). The authors concluded that fibrosis progressed faster in participants with versus without T2DM and that these findings have important implications for clinical practice and trial design.

Huang DQ, Wilson LA, Behling C, et al. Fibrosis progression rate in biopsy-proven nonalcoholic fatty liver disease among people with diabetes versus people without diabetes: A multicenter study. Gastroenterology. 2023;165(2):463–472.

Correspondence: Dr. Rohit Loomba at roloomba@ucsd.edu