Expression of Cdc2 and cyclin B1 in Helicobacter pylori-associated gastricMALT and MALT lymphoma - Relationship to cell death, proliferation, and transformation

Mucosa-associated lymphoid tissue (MALT) may accumulate within gastric muco sa as a result of long standing Helicobacter pylori infection, and this acq uired MALT may eventually develop into low-grade B-cell MALT lymphoma, To d etermine the possible association of cell cycle regulatory proteins and apo ptotic cell death in the transformation of H, pylori gastritis to MALT lymp homa, the extent of cell proliferation, cell viability, expression of Cdc2/ Cdk1 and cyclin B in gastric mucosal from patients with H. pylori-positive chronic gastritis (n = 7), MALT (n = 12), or MALT lymphoma(n = 12) were und ertaken. Control tissue was obtained from H, pylori negative patients (n = 5) Proliferating cell nuclear antigen (PCNA), Cdc2, and cyclin B1 were exam ined in paraffin embedded tissue by immunohistochemistry, while the apoptot ic index (AI) was determined using the TUNEL assay. H&E staining for histol ogy and modified Giemsa staining for the detection of H. pylori was conduct ed simultaneously. When compared to chronic gastritis tissue, those with MA LT or MALT lymphoma had an increase in PCNA. labeling index of 3.3- and 2.7 -fold, while that for Cdc2/Cdk1 increased 2.3- and 3.1-fold, respectively. cyclin B1 labeling was 1.9 and 3.0 fold, while the AI was 3.4- and 1.4-fold higher in MALT and MALT lymphoma tissue, respectively, in the same compari son. On the other hand, the AT index of MALT lymphoma was 2.5-fold lower th an that for MALT tissues. The labeling scores for Cdc2/Cdk1 and cyclin B1 m ere significantly higher in the germinal center when compared to the mantle and marginal zones of MALT tissues. Using chi(2) and Pearson/Spearman's rh o correlation coefficient with regression analyses, there was an inverse co rrelation between the Al and Cdc2/Cdk1 or cyclin B1 in MALT and MALT lympho ma tissues. There was no correlation between AI and PCNA labeling in ally o f the tissues. These results suggest that Cdc2/Cdk1 and cyclin B1 expressio n may be actively associated in the modulation of cellular death by apoptos is, as well as cellular proliferation and transformation during the evoluti on of H. pylori-associated gastritis to MALT lymphoma. Subclassification of high labeling score (greater than or equal to 40) for Cdc2/Cdk1 and cyclin B1 and low labeling index (<0.6) for apoptotic cells in H. pylori-associat ed MALT may help in identifying a population of patients with an increased risk of developing MALT lymphoma.