OA: Clinicopathologic Characteristics of Microsatellite Instable Gastric Carcinomas

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Clinicopathologic Characteristics of Microsatellite Instable Gastric Carcinomas Revisited: Urgent Need for Standardization  Applied Immunohistochemistry & Molecular Morphology

 Study Population
From the archive of the Institute of Pathology, University Hospital Kiel, we identified all patients who had undergone either total or partial gastrectomy for adenocarcinomas of the stomach or esophagogastric junction between 1997 and 2009 (GC cohort)....

 ...However, the youngest patient of our cohort with MSI-GC was 58 years old, making GC as first presenting tumor of a Lynch syndrome less likely. GC as first and only presenting tumor of a Lynch syndrome occurs in <1% of Lynch syndrome patients.⁵¹

 As for other tumor types, the reasons for better survival remain ill defined. It has been suggested that MSI leads to the attraction of tumor-infiltrating lymphocytes, and a tumor-suppressive immune response.22,3

Abstract
Microsatellite instable gastric cancer (MSI-GC) is a specific molecular subtype of GC. We studied the phenotypes, genotypes, and clinicopathologic characteristics of MSI-GC in a white GC cohort and compared our findings with an extended literature review. The study cohort consisted of 482 patients. Specimens were available from 452 cases and were used for immunostaining (MLH1, PMS2, MSH2, MSH6) and molecular biological analyses (BAT-25, BAT-26, NR-21, NR-24, NR-27; Epstein-Barr virus in situ hybridization). Thirty-four (7.5%) GCs were MSI. Loss of MLH1 and/or PMS2 was found in 30 (88%) MSI-GC, 3 (9%) showed loss of MSH2 and/or MSH6. One (3%) MSI-GC was identified only by molecular biological testing. A single case was heterogeneous and contained microsatellite-stable and instable tumor areas. Twenty-one (62%) MSI-GCs showed unusual histologic features. MSI-GC was not found in diffuse-type or Epstein-Barr virus-positive GC. MSI-GC was significantly more prevalent in elderly patients, distal stomach, and was associated with a significantly lower number of lymph node metastases and a significantly better overall and tumor-specific survival. MSI-GC constitutes a small but relevant subgroup of GC with distinct clinicopathologic characteristics. Our literature review illustrates the shortcomings of missing standardized testing algorithms with prevalences of MSI-GC ranging from 0% to 44.5%. Future studies should test the hypothesis that patients with MSI-GCs may not need adjuvant/perioperative chemotherapy. However, this will require a standardized, quality-controlled diagnostic algorithm of MSI for GC.