Decrease of serum total ghrelin in extensive atrophic gastritis: comparison with pepsinogens in histological reference.

OBJECTIVE: Ghrelin is mainly secreted by the gastric oxyntic mucosa and its production is impaired in chronic atrophic gastritis. This study aimed at evaluating how serum total ghrelin correlates with the extent of atrophy, and to compare its performance as a serologic marker with that of pepsinogen (PG). MATERIAL AND METHODS: Data were collected from 154 patients with atrophic gastritis. The histological extent of atrophy was assessed by three paired biopsies from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Fasting serum concentrations of total ghrelin, pepsinogen I and II were measured. Regression analysis was performed to evaluate the factors associated with serum total ghrelin. The serologic performance was compared with that of pepsinogen using receiver-operating characteristic (ROC) curves. RESULTS: The Helicobacter pylori infection rate was 85%, and extensive atrophic gastritis involving CGC was found in 24%. Serum total ghrelin was significantly decreased in patients with extensive CGC atrophy (median: 170.4 pg/mL, vs 201.1 pg/mL in patients without atrophy; p < 0.001), and its levels correlated with those of pepsinogen I and I/II ratio. The decrease of serum total ghrelin was independent of age, gender, body mass index (BMI), and H. pylori infection status. The sensitivity and specificity of serum total ghrelin in predicting extensive atrophy were 57% and 79%, respectively. The discriminatory ability was similar to that of pepsinogen I/II ratio (p = 0.612), and lower than that of pepsinogen I (p = 0.040). CONCLUSIONS: Serum total ghrelin is decreased during extensive atrophy involving CGC. The serologic performance is lower than that of pepsinogen I.

Clinicopathologic and genomic features of high-grade pattern and their subclasses in lung adenocarcinoma.

INTRODUCTION: Recent lung adenocarcinoma (LUAD) grading system proposed by the International Association for the Study of Lung Cancer (IASLC) has emphasized the proportion of high-grade patterns (HGPs). We aimed to evaluate the clinicopathologic and genomic characteristics associated with HGP which has not yet been fully investigated. METHODS: Tissue samples from 174 patients who underwent surgical resection of LUAD from January to December 2015 were histologically evaluated. Proportions of HGPs, including solid, micropapillary, cribriform, and complex glandular patterns, were individually quantified. Prognostic implications of HGP proportion, both as a continuous variable and as subclasses divided by cutoffs of 20%, 50%, and 90% (low-intermediate grade [LIG], HGP <20%; high grade 1 [HG1], 20-<50%, HG2, 50-<90%; HG3, ≥90%) were evaluated. Different clinicopathologic factors and genomic alterations according to the HGP subclasses were assessed. RESULTS: Relative hazards of the HGP gradually elevated as its proportion increased over 20%, the cut-off value established by the IASLC grading system, and the cancer-specific overall survival (OS) of HG1 subclass was not significantly decreased compared to the LIG subclass on univariate analysis. However, further subgrouping showed significantly increased frequencies of male, advanced stage tumors, lymphovascular invasion, and spread through alveolar space in higher HGP subclasses. Also, common LUAD driver mutations, particularly EGFR mutations, were less frequent, whereas alterations in TP53 and cell cycle pathway-related genes were more frequent. Higher HGP subclasses and TP53 gene alteration were associated with shorter cancer-specific OS and RFS in multivariate survival analysis. CONCLUSIONS: HGP subclasses of LUAD displayed distinct clinicopathological characteristics and genomic alterations, including TP53 and cell cycle pathway, emphasizing the clinical value of these subclasses in LUAD. Higher HGP subclass and alteration in TP53 may be markers of poor post-operative survival.