Nuclear overexpression of bcl-2 oncoprotein during the progression of human stomach cancer.

We unexpectedly observed strong nuclear overexpression of bcl-2 protein in advanced stomach cancer. As far as we know, such expression has not yet been reported. To investigate the significance of nuclear expression of bcl-2 protein in gastric carcinoma, we immunohistochemically analyzed bcl-2 overexpression in a gastric carcinogenic sequence, including 19 tubular adenomas (TA), 20 early carcinomas (EGC), and 20 advanced carcinomas (AGC). While TA displayed a specific granular and supranuclear cytoplasmic staining pattern, adenocarcinomas showed a strong nuclear staining pattern. Nuclear staining of bcl-2 was observed in 50% of AGC, 30% of EGC, and 10% of TA; cytoplasmic staining, on the other hand, was observed in all TA, 5% of EGC, and 10% of AGC. Nuclear bcl-2 overexpression differed according to the histologic type of AGC, occurring in 67% of the diffuse type and 25% of the moderately-to-well differentiated type. In the diffuse type, nuclear bcl-2 positive AGC predominated. In metastatic lesions, the pattern of bcl-2 immunostaining was almost identical to that seen in primary tumor. These results suggest that nuclear expression of bcl-2 may be related to malignant transformation in the stomach and is frequently associated with diffuse type advanced gastric adenocarcinomas.