title: Immunoreactivity for cyclin D3 is frequently detectable in high-grade primary gastric lymphomas in the absence of the t(6;14)(p21.1;q32.3) chromosomal translocation.
abstract: Cyclin D3 plays a pivotal role in controlling the physiological progression from the G1 to the S phase of the cell cycle. Recent data suggest that cyclin D3 may be deregulated in extranodal non-Hodgkin's lymphomas (NHLs) as a consequence of the t(6;14)(p21.1;q32.3) translocation. The present study investigated for the first time by dual-colour fluorescence in situ hybridization (FISH) on interphase nuclei and immunohistochemistry the prevalence of the t(6;14) translocation and cyclin D3 immunoreactivity (IR) in a series of 29 stage I-IIE primary gastric NHLs (PGLs). No case showed the t(6;14) translocation. However, in five (17.2%) cases (two extranodal marginal zone lymphomas of MALT type, LGM; one diffuse large-cell lymphoma with a MALT component, DLCLM; and two diffuse large-cell lymphomas without a MALT component, DLCL), three to four cyclin D3 signals were detected by FISH. Co-hybridization with probes specific for the centromeric region and long arm of chromosome 6 indicated trisomy in one case (DLCL), whereas in the remaining four cases the pattern was highly suggestive of the presence of an isochromosome 6p. One (12.5%) case of LGM, six (75%) cases of DLCLM, and seven (53.8%) cases of DLCL (p = 0.0378) were immunoreactive for cyclin D3. Cyclin D3 IR was detected in two (40%) of the five cases with extra cyclin D3 signals and in 12 of the remaining 24 cases (50%, p = 1.000). These results suggest that the t(6;14) may represent a rare event in the pathogenesis of PGL and that cyclin D3 deregulation is most likely the result of epigenetic mechanisms.
authors.affiliation: Divisions of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Roberta
authors.initials: R
authors.lastname: Fasani
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Curto
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.forename: Barbara
authors.initials: B
authors.lastname: Pozzi
authors.forename: Teresio
authors.initials: T
authors.lastname: Motta
authors.forename: Salvatore
authors.initials: S
authors.lastname: Andreola
authors.forename: Andres J M
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; D009363:Neoplasm Proteins