Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

Abstract

An abnormal expression of cyclin D3, a key regulator of the cell cycle, has been documented in a variety of human malignancies, and the cyclin D3 gene, mapping to 6p21, may be deregulated in plasma cell myeloma and non-Hodgkin's lymphoma as a result of the t(6;14)(p21.1;q32.3) translocation and/or gene amplification. In the current study, we for the first time investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) the prevalence of cyclin D3 abnormalities in follicular lymphomas (FLs), comparing the results with traditional clinicopathologic characteristics, p27 and skp2 immunoreactivity (IR) and Ki-67 labeling index (LI). Cyclin D3, skp2 and Ki-67 IR significantly increased from grade I to grade III FL (p ‫؍‬ 0.0003, p ‫؍‬ 0.0001 and p < 0.0001, respectively), while p27 IR was significantly (p < 0.0001) more prevalent in low-grade tumors. Cyclin D3 IR was directly correlated with the Ki-67 LI (p < 0.0001) and inversely correlated with p27 IR (p ‫؍‬ 0.050). None of the 13 cases analyzed by FISH showed the t(6;14) translocation, but in 2 (15.3%) grade I FLs 3 cyclin D3 signals were detected. Cohybridization with probes specific for the centromeric region and the long arm of the chromosome 6 indicated trisomy in one case and a pattern highly suggestive for the presence of an isochromosome 6p in the other case. Our data suggest that the t(6;14) translocation may be extremely uncommon in FL and that a deregulated expression of cyclin D3, possibly due to epigenetic mechanisms, may be involved in the pathogenesis of high-grade tumors.

Lymphomas of the head and neck in the pediatric population

“…Moreover, although surface staining with Ki-67 monoclonal antibody was significantly more frequent in high-grade lymphomas and associated with a negative prognostic factor in 29 patients with head and neck lymphomas [26], we did not observe a relationship between Ki-67 labeling index and survival outcomes. Because Ki-67 staining may be a marker for grade rather than an independent predictor of outcome, its significance as a prognostic indicator in pediatric head and neck lymphomas remains speculative [16,27,28].…”

Differential expression of cyclin D3 in ALK+ and ALK− anaplastic large cell lymphoma

“…Overexpression of cyclin D3 also has been associated with gene amplification and has been detected by immunohistochemistry in a subset of cases of plasma cell myeloma, follicular lymphoma, and diffuse large B-cell lymphoma, as well as in nonhematologic malignancies [15,[35][36][37][38][39][40][41].…”

Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine‐needle aspirates suspicious for Hurthle cell neoplasms

“…Cyclin D3 overexpression in human tumors is not restricted to the thyroid. Indeed, it is implicated in such solid and hematologic malignancies as high-grade non-Hodgkin lymphoma, 24,25 gastrointestinal stromal tumors, 26 laryngeal carcinomas, 27 and renal carcinomas. 28 The 6p21 locus, which harbors the cyclin D3 gene, may be amplified or involved in the t(6;14)(p21.1;q32.3) translocation.…”