Nuclear Expression of BCL10 or Nuclear Factor Kappa B Predicts Helicobacter pylori–Independent Status of Early-Stage, High-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphomas

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Abstract
A high percentage of early-stage, high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori dependent. t(11;18)(q21;q21), a genetic aberration highly predictive of H pylori–independent status in low-grade gastric MALT lymphoma, is rarely detected in its high-grade counterpart. This study examined whether nuclear expression of BCL10 or nuclear factor kappa B (NF-κB) is useful in predicting H pylori–independent status in patients with stage IE high-grade gastric MALT lymphomas. Twenty-two patients who had participated in a prospective study of H pylori eradication for stage IE high-grade gastric MALT lymphomas were studied. The expression of BCL10 and NF-κB in pretreatment paraffin-embedded lymphoma tissues was evaluated by immunohistochemistry and confocal immunofluorescence microscopy. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. Aberrant nuclear expression of BCL10 was detected in seven (87.5%) of eight H pylori–independent and in none of 14 H pylori–dependent high-grade gastric MALT lymphomas (P < .001). All seven patients with nuclear BCL10 expression had nuclear expression of NF-κB, compared with only two of 15 patients without nuclear BCL10 expression (P = .002). As a single variable, the frequency of nuclear expression of NF-κB was also significantly higher in H pylori–independent tumors than in H pylori–dependent tumors (seven of eight [87.5%] v two of 15 [12.3%]; P = .002). The API2-MALT1 fusion transcript was detected in only one (12.5%) of eight H pylori–independent lymphomas. Nuclear expression of BCL10 or NF-κB is highly predictive of H pylori–independent status in high-grade gastric MALT lymphoma, and coexpression of these two markers in the nuclei is frequent.