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Determinants of Signet Ring Cell Carcinoma in Hereditary Diffuse Gastric Cancer

Ophir Gilad, MD, CGA-IGC Communications Committee

Hereditary diffuse gastric cancer (HDGC), related to mutations in the CDH1 increases the risk of gastric cancer in those affected. While prophylactic total gastrectomy is an option to reduce the risk of cancer, endoscopy may be a screening option. One concern is that most individuals with HDGC have Signet Ring Carcinoma Cells (SRCC) in their stomach, but not all of them will go on to progressive, invasive cancer.

In an abstract presented at the presidential plenary at the 2023 CGA-IGC annual meeting, Dr. Ophir Gilad and colleagues at the University of Chicago looked into risk factors for invasive disease.

The study looked at 67 individuals with HDGC, 47 undergoing endoscopy and 20 who had gastrectomy. In the individuals undergoing endoscopic screening, no clinical or endoscopic findings were associated with finding SRCC. Under the microscope, intestinal metaplasia (IM) on biopsies was associated with finding SRCC. In the patients undergoing surgery, 2 patients had invasive disease and both had IM and SRCC found on the first endoscopy prior to surgery. Staining for p53 or Ki67, markers of disease risk, were not different between individuals.

In sum, the authors found that IM and SRCC on first endoscopy were associated with invasive disease. These findings haven’t been seen in other cohorts but most excitingly the authors have initiated a collaborative retrospective consortium to validate predictors of invasive disease to better risk stratify HDGC patients for surgery or endoscopic surveillance and invited other centers to join.

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