Background/Purpose: miR200b
miRNAs (miR200b-3p and miR200b-5p) are critical regulators of the expression of
oncogenes and tumour suppressor genes. Herein, we sought to investigate whether
their expression in salivary gland tissues (SG) is related to SS-related
lymphoma development.

Methods: miR200b-3p
and miR200b-5p expression in SG tissues was analyzed by real-time PCR in total
RNA from 30 SS patients (all women), including 20 patients that did not develop
SS-lymphoma during follow up (lymphoma(-); median follow up time since biopsy
performance, range: 3.8yrs, 3.4-10yrs), 6 patients that develop MALT-lymphoma
in the future (prelymphoma; median follow up time till lymphoma diagnosis, range:
4.0yrs, 1.0-5yrs) and 4 patients that had MALT-lymphoma at the time of biopsy (lymphoma).
Significant differences in miR expression between SS subgroups were analysed by
Tukey’s multiple comparison test, whereas associations with other histologic
futures by Mann-Whitney test.

Results: miR200b-5p,
but not miR200b-3p, was significantly down-regulated in SG tissues of
prelymphoma (p≤0.01) and lymphoma (p≤0.01) SS patients compared to
lymphoma(-) SS patients (mean relative expression±SE: 2.97±1.09, 2.24±0.75 and 14.67±1.76,
respectively) (Figure). On the contrary, miR200b-3p levels in SGs were
significantly reduced in SS patients with SG infiltrates that organize into
ectopic germinal centres (GC) compared to those without (1883±682 vs 51090±28330,
p=0.05, respectively).

Conclusion: The
significantly lower expression of miR200b-5p in SS patients that had or
developed SS-related MALT lymphoma in the future implicates it in
lymphomagenesis, whereas its significant downregulation in prelymphoma SGs
possibly suggests that miR200b-5p represents a potential prognostic marker for
future lymphoma development. Evaluation of its expression in a larger cohort is
needed. Finally, considering that GC formation has been linked to
lymphomagenesis, the deregulated expression of its paired miRNA, miR200b-3p, in
SS patients with GCs could represent a continuum of lymphomagenesis.