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From the Molecular Gastroenterology & Pancreatic Cancer Research
Unit*
and the Department of
Pathology,
The Department of Veterans Affairs
Medical Center, Kansas City, Missouri; and the Department of
Medicine,
University of Kansas Medical
Center, Kansas City, Kansas
Mucosa-associated lymphoid tissue (MALT) may accumulate within
gastric mucosa as a result of long standing Helicobacter
pylori infection, and this acquired MALT may eventually
develop into low-grade B-cell MALT lymphoma. To determine the possible
association of cell cycle regulatory proteins and apoptotic cell death
in the transformation of H. pylori gastritis to MALT
lymphoma, 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 undertaken. Control tissue was
obtained from H. pylori- negative patients
(n = 5). Proliferating cell nuclear antigen
(PCNA), Cdc2, and cyclin B1 were examined in paraffin
embedded tissue by immunohistochemistry, while the apoptotic
index (AI) was determined using the TUNEL assay. H&E staining for
histology and modified Giemsa staining for the detection of H.
pylori was conducted simultaneously. When compared to chronic
gastritis tissue, those with MALT 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 comparison. On the other
hand, the AI index of MALT lymphoma was 2.5-fold lower than
that for MALT tissues. The labeling scores for Cdc2/Cdk1 and cyclin B1
were significantly higher in the germinal center when compared to the
mantle and marginal zones of MALT tissues. Using 
2 and
Pearson/Spearman’s rho correlation coefficient with regression
analyses, there was an inverse correlation between the AI and
Cdc2/Cdk1 or cyclin B1 in MALT and MALT lymphoma tissues. There was no
correlation between AI and PCNA labeling in any of the tissues. These
results suggest that Cdc2/Cdk1 and cyclin B1 expression may be actively
associated in the modulation of cellular death by apoptosis, as
well as cellular proliferation and transformation during the evolution
of H. pylori-associated gastritis to MALT lymphoma.
Subclassification of high labeling score (
40) for Cdc2/Cdk1 and
cyclin B1 and low labeling index (<0.6) for apoptotic cells in
H. pylori-associated MALT may help in identifying a
population of patients with an increased risk of developing MALT
lymphoma.
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