LAUSR

The interesting study by Ryoji Kushima and coauthors [1] adds new insights to the clinicobiological profiling of the pseudopyloric (PPM) transformation of the natively oxyntic gastric glands. In particular, the design of the study deals with the oxyntic glands’ metaplasia in the model of Helicobacter pylori (H. pylori) gastritis; the study also addresses the longterm outcome of PPM following H. pylori eradication. The importance of this study resides on its focus on two major issues. The first is the metaplastic phenotype and immunophenotype of the oxyntic glands and the changes of the native parietal cells into mucosecreting epithelia. The second, and more intriguing one, is the potential reversibility of the newly acquired cell commitment. Both issues require some additional considerations about the clinicopathological importance of including the evaluation of these metaplastic changes in the histological assessment of gastric mucosal atrophy and its related gastric cancer risk. To clarify the current knowledge, and what is still ignored, about PPM, I will outline a brief account of how the biology of pseudopyloric metaplasia has been viewed during the last four decades. In 1982, Takanori Hattori in his study titled “Morphology and cell kinetics of the pseudo-pyloric glands” addressed the subject of the mucosecreting metaplasia of the oxyntic glands and proposed to the international literature the “pseudo-pyloric” label [2]. This seminal study, that used cryosurgically damaged oxyntic mucosa of Wistar rats, provided experimental evidence to the hypothesis advanced by Ludwig Moszkowicz, who considered the metaplastic epithelium as “false regeneration” occurring in the biological setting that is currently defined as “repair” [2, 3]. Ten years later, Sir Nicholas Wrigth further reinforced the repair profile of the ulcer-associated cell lineage (UACL) as featured in the oxyntic gastric mucosa [4]. By using both immunohistochemistry and in situ hybridization in gastric mucosa from stomachs with ulcers, Wrigth and coworkers demonstrated the expression of trefoil peptides pS2 (currently defined as TFF1), human spasmolytic polypeptide (hSP, coded by the SP gene, later renamed TFF2) and hSP mRNA in gastric oxyntic glands. The study also emphasized the “intimate (topographical) relationship” of the mucosecreting foveolar-type epithelium with parietal cell [5]. In 2002, Farrell and coworkers showed an inverse association between the TFF2 concentration in gastric secretions and gastric acid output [4]. In particular, the model of TFF2-deficient mice suggested “a physiologic role for TFF2 to promote mucosal healing through the stimulation of proliferation and downregulation of gastric acid secretion” [4]. This last finding, initially interpreted as due to a parietal cell inhibition to promote wound healing, could be critically reinterpreted as resulting from the replacement of the native parietal cells population by TFF2promotedmetaplastic pseudopyloric epithelium, a condition currently included within the spectrum of gastric mucosal atrophy. On the whole, this body of data supports the reliability of TFF2 as marker and promoter of the pseudopyloric transformation of parietal cells, which ultimately results in impaired hydrochloric acid secretion. Such an interpretation is in keeping with the UACL-origin of PPM as triggered by any injury targeting the parietal cells, including both environmental agents (H. pylori) or host-related pathological conditions (autoimmunity). Most recently, within the spectrum of the mucosecreting metaplasia of the oxyntic glands, a new immunophenotype has been described as spasmolytic expressing metaplasia (SPEM). * Massimo Rugge [email protected]