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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.

Adenoma malignum (AM) is known to be one of the malignant tumors that is commonly associated with Peutz-Jeghers syndrome. Recently, the genetic locus of Peutz-Jeghers syndrome was mapped to the telomeric region of chromosome 19p. We analyzed nine sporadic cases of AM with high-density loss of heterozygosity to study the region of chromosome 19p13.2-13.3 using eight microsatellite markers. Our deletion mapping data revealed a distinct region with 100% loss of heterozygosity frequency at marker D19S216. This result indicates that a putative tumor suppressor gene for AM is located at D19S216 on chromosomal band 19p13.3 and plays an important role in AM tumorigenesis.

Biochanin A was studied for its capacity to inhibit benzo(a)pyrene (BP) induced neoplasia in female Swiss Webster mice. To investigate the effect of biochanin A on the initiation step, biochanin A (500 mg/kg) was administered orally 48 hours prior to BP (3 mg/mouse), which was also given orally. This sequence of biochanin A and BP administration was repeated once a week for a total of 4 weeks. At 26 weeks after the last treatment, all the mice were sacrificed. To investigate the effect of biochanin A on the promotion step, a single subcutaneous injection of 0.5 mg of BP was given within 24 hours after birth, and biochanin A (0.125 mg/mouse) was injected intraperitoneally 3 times a week for 6 weeks after weaning. In the initiation protocol, the concomitant administration of biochanin A showed significant inhibition of the mean number of lung tumors (P less than 0.001) and the incidence of carcinoma of the forestomach (P less than 0.02). In the promotion protocol, biochanin A significantly inhibited the incidence (P less than 0.01) and the multiplicity (P less than 0.001) of pulmonary adenoma, compared with the group treated with BP alone. These results suggest that biochanin A inhibitory potential in the initiation, as well as in the promotion step of BP carcinogenesis in female Swiss-Webster mice.