Abstract
Background: Several studies have evaluated various histologic predictors of invasion in breast and colon cancer biopsies. However, possible predictive factors of submucosal invasion in early gastric carcinomas have not been investigated. Identifying pathologic factors to predict submucosa invasion from pretreatment gastric biopsies would help select patients who may benefit from endoscopic mucosal resection (EMR). Methods: Pretreatment gastric biopsies from 60 patients with early gastric carcinomas with submucosal invasion who underwent EMR between 2002 and 2007 were reviewed. As a control, biopsies from 58 patients with intramucosal gastric carcinomas taken during the same period were evaluated. For validation of the results, another 702 gastric biopsies treated and confirmed as pT1 gastric carcinomas were also reviewed. For statistical analyses, Chi-square test, Fisher's exact test using permutation method for multiple testing, and multiple logistic progression tests were used. Results: The depth of submucosa invasion varied from 50 μm to 3000 μm (mean 949 μm). In the biopsy specimens of carcinoma with submucosa invasion, differentiated histology, histologic heterogeneity, islands of muscularis mucosa, cribriform pattern, papillary feature, desmoplastic reaction, and intraglndular eosinophilic necrotic debris (IEND) were observed in 96.7%, 36.7%, 16.7%, 16.7%, 23.3%, 40%, and 46.7% of cases, respectively, compared to 100%, 5.2%, 0%, 1.7%, 5.2%, 19%, and 22.4% of intramucosal carcinoma biopsies. In multivariable analyses, histologic heterogeneity [odds ratio (OR), 9.59, p=0.002], IEND [OR, 6.23, p= 0.012], cribriform pattern [OR, 4.66, p=0.03], and papillary feature [OR, 5.52, p=0.018] were significantly associated with submucosal invasion in EMR specimens. In the validation cohort, histologic heterogeneity remained significant (p=0.003) with 48.7% sensitivity and 72.2% specificity, with positive predictive value of 43.5% [95% confidence interval (36.9%, 50.1%)] and negative predictive value of 75.3% [95% confidence interval (71.1%, 79.5%)]. Conclusion: In pretreatment gastric biopsies, histologic heterogeneity is a significant pathologic predictor of submucosal invasion. Additional prospective studies are warranted to find more sensitive and specific markers.
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