Abstract
Dear Editor
I read with great interest the recent systematic review and meta-analysis by Benites-Goñi et al., 1 which provides valuable insight into the utility of the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) staging systems in predicting gastric cancer (GC) risk. However, this study also highlights a broader and ongoing challenge in the study of gastric precancerous lesions: the inconsistent and often conflated reporting of gastric atrophy (GA) and gastric intestinal metaplasia (GIM). This diagnostic ambiguity hinders accurate GC risk estimation, particularly for GA, which may represent a reversible stage in the Correa cascade, unlike GIM, which is widely considered irreversible.
Several studies in the literature do not clearly distinguish between GA and GIM. For instance, Zhang et al., 2 Lahner et al., 3 and Vannella et al. 4 report GA based on histological findings which do not adequately exclude coexisting GIM. This lack of diagnostic precision complicates risk stratification and may obscure true associations between GA and the development of GC.
A critical contributing factor lies in the histopathological framework underpinning these assessments. The Updated Sydney System, foundational to OLGA and OLGIM staging, includes GIM within the definition of atrophy severity. 5 While this may be practical in clinical settings, it creates significant limitations in research contexts where the distinct biological behavior of GA and GIM must be clarified. Without strict separation between these lesions, the natural history and progression risk of each remain poorly defined.
To address this, a revised diagnostic system could be considered, particularly for research purposes, in which GA and GIM are categorically distinguished. A promising approach involves the routine use of mucin immunohistochemistry. This method leverages the differential expression of mucin core proteins: gastric-type mucins such as MUC5AC (surface foveolar cells) and MUC6 (deep glandular mucous cells) are preserved in pure GA, while intestinal-type mucins, particularly MUC2, are characteristically expressed in GIM. 6 The presence of CD10 may also help identify absorptive brush-border enterocyte-like features in GIM. Incorporating these markers into histopathological evaluation can facilitate more confident identification of “pure” GA versus intestinal metaplasia.
Such refinements are especially important in Western populations, where data on GA’s distribution and its independent risk of progression to GC remain limited. Current evidence, drawn from studies that inadequately distinguish GA from GIM, may misrepresent the cancer risk posed by extensive or antral-predominant GA.
Ultimately, improving the precision of GA diagnosis is fundamental to more accurate GC risk modeling. Clearer classification can help identify reversible disease stages, guide surveillance more effectively, and deepen understanding of gastric carcinogenesis.
