Differential diagnosis of atypical epithelium of biopsied gastric mucosa using immunostaining of Ki-67, p53, hMLH1 and MDM2 expression.

Gastric biopsy specimens were classified from category 1 (C1) to C5 according to the Vienna classification of gastrointestinal epithelial neoplasia. Fifty cases of C1, 40 cases of C2, 29 cases of C3, 19 cases of C4-1, 20 cases of C4-2+3, and 24 cases of C5 were selected and the expression of Ki-67, p53, hMLH1, and MDM2 was examined immunohistochemically to obtain useful data for the differential diagnosis of controversial cases of C2 and C4. The C2 cases, which did not show definitive neoplasia, were divided into two groups: one group had regenerative epithelium showing a relatively high degree of atypia (regenerative atypia: RA) and the other had carcinoma showing a mild degree of atypia (carcinoma of low grade atypia: CLGA). There were 0/23 RA and 12/17 CLGA cases that were positive for p53. Ki-67-positive cells were localized in the mitotic cell zone in RA, whereas they were irregularly distributed in CLGA. None of the cases of high-grade adenoma (C4-1) showed p53 expression, whereas 19 out of 44 well-differentiated adenocarcinoma cases (C4-2+3 and C5) were positive for p53. Ki-67-positive cells were localized in the mitotic cell zone in C4-1, whereas they were irregularly distributed in C4-2+3. hMLH1 was expressed in the proliferative cell zone of the normal foveolae, in all of the cases of adenoma (C3, C4-1) and in most cases of adenocarcinoma (C4-2,3 and C5). However, in 3 cases of C4-2+3, which showed a relatively mild degree of cellular atypia and were difficult to differentiate from high-grade adenoma (C4-1), the neoplastic cells were completely negative for hMLH1. MDM2 showed no characteristic expression in any gastric lesion. In conclusion, p53-positive cases of C2 and C4 were highly suggestive of carcinoma. Even if the case was negative for p53, the irregular distribution pattern of Ki-67-positive cells was highly suggestive of carcinoma. hMLH1-negativity in the C4 cases is strongly suggestive of carcinoma and this may be an useful marker for differentiating C4-2+3 from C4-1.