Introduction: Endoscopic submucosal dissection is widely employed in early gastric cancer (EGC). Foveolar phenotypes should be distinguished from the other differentiated EGC (DEGC) types because of their increased malignant potential. The phenotypic classification could be useful not only for investigating EGC tumorigenesis but also for evaluating the tumor aggressiveness to guide treatment decision making. Methods: On surgical tissue specimens, we studied the mucin phenotype of EGC to distinguish cases with a worse prognosis dictating different therapeutic options or a very close surveillance program. DEGC in our series were classified as mucin foveolar (51%) or mucin intestinal (49%) phenotype. We evaluated correlations among foveolar and intestinal phenotypic markers, tumor patterns, clinicopathologic features and prognostic and therapeutic implications. Immunohistochemistry (IHC) for MUC5AC and CDX2 was performed on 63 EGC patient specimens. MUCA5C was employed as gastric foveolar phenotypic marker and CDX2 as intestinal phenotypic marker. Results: Foveolar DEGC was significantly associated with larger tumor size (p=0.01), high grade (G2-G3) (p=0.001), vessel permeation (p=0.05), lymph node metastasis (p=0.001) and ulceration (p=0.001), whereas intestinal type DEGC was associated with low grade (p=0.001). Conclusion: IHC determination of the mucin phenotype is an easy, inexpensive method that can provide useful, sensitive markers distinguishing the foveolar or intestinal phenotype in DEGC. The precise identification of the foveolar type, featuring a poorer prognosis, should sound a warning bell mandating very close study of the lesion before endoscopic treatment or contraindicating endoscopic resection in favor of the open surgery option.
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