Analysis Of Prognostic Value Of Biomarkers In Gastric Malt Lymphomas.

JOURNAL OF CLINICAL ONCOLOGY(2010)

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摘要
e14552 Background: 80% of MALT lymphomas regress in response to H. pylori eradication therapy. Molecular mechanisms of resistance to H. pylori eradication therapy and resistance to more aggressive therapies such as chemo- and radiotherapy remain unclear. To clarify this issue, we investigated H. pylori infection status, FOXP1 expression, microsatellite instability (MSI), and the t(11;18)-status in 29 patients with gastric low-grade MALT lymphoma. Methods: 29 gastric MALT lymphomas, diagnosed between 2003 and 2009, were retrieved from the archives of our Department of Pathology. All cases were clinically documented and further investigated by immunohistochemistry for the presence/absence of H. pylori, presence/absence of FOXP1 expression, presence/absence of BCL10 expression, and the presence/absence of MSI (MLH1, MSH2, MSH6), as well as by RT-PCR for the presence/absence of t(11;18). Results: 7/29 gastric MALT lymphomas (24%) were positive for t(11;18). The latter cases were positively associated with nuclear BCL10 expression. H. pylori was detected in 16/29 gastric MALT lymphomas (55%). No response to H. pylori eradication therapy was observed in 37.5% (6/16) of H pylori-positive cases : 3/3 or 100% in the t(11;18)-positive cases, compared to 3/13 or 23% in the t(11;18)-negative cases. In the group of H pylori-negative lymphomas, relapse or resistance to first line therapy was observed in 5 of 11 treated cases (45%) : 4/4 or 100% in the t(11;18)-positive cases, compared to 14% or 1/7 in the t(11;18)-negative cases. 10/29 gastric MALT lymphomas (34%) showed moderate to strong nuclear FOXP1 expression, 6 of them being H pylori positive. All 3 t(11;18)-negative lymphomas not responding to H. pylori eradication showed a strong nuclear FOXP1 expression, compared to only 1 of 10 cases (10%) in the responding group. Interestingly, 6/29 (20%) cases, all of them being t(11;18)-negative, showed absence for one or more of the DNA mismatch repair enzymes. Conclusions: In gastric MALT lymphoma the presence of t(11;18) predicts resistance to or relapse after first-line therapy. In t(11;18)-negative cases, FOXP1 expression predicts resistance to H. pylori eradication therapy. MSI may represent an alternative pathway for t(11;18)-negative MALT lymphomas. No significant financial relationships to disclose.
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gastric malt lymphomas,biomarkers,prognostic value
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