title: Chromosomal translocations t(4;14), t(11;14) and proliferation rate stratify patients with mature plasma cell myelomas into groups with different survival probabilities: a molecular epidemiologic study on tissue microarrays.
abstract: Plasma cell myelomas (PMs) exhibit clinical and molecular heterogeneity. To date, morphology and immunohistochemistry on bone marrow trephines are of limited value to stratify patients into different prognostic categories. However, some chromosomal translocations are of prognostic and/or of predictive importance in PMs. In this study, the prognostic significance of morphology, CyclinD1 expression, proliferation index (Mib1) and presence of the translocations FGFR3/IgH [t(4;14)] and CCND1/IgH [t(11;14)] are compared in 119 patients with PM. Immunohistochemistry and fluorescence in situ hybridization analysis were carried out on a tissue microarray containing bone marrow trephines. Hundred and one PMs showed a mature morphology whereas 10 were immature. All but one PM carrying a translocation showed a mature morphology. Patients with a t(4;14) (12%) had a statistically significant shorter 1-year survival (P=0.004), whereas those with a t(11;14) (21%) had a trend towards a better clinical outcome. CyclinD1 protein expression was not significantly associated with survival. Besides the t(4;14), an immature morphology (P<0.001) and a proliferation index (Mib1) of more than 10% (P=0.002) were associated with a significantly worse outcome. A high occurrence of strong CyclinD1 protein expression in the tumor cells was predictive of either a t(11;14) or of a low level amplification of the CCND1 gene, suggesting that different molecular mechanisms may have lead to an over-expression of the CyclinD1 protein in PMs. These findings demonstrate that a high proliferation rate and translocations involving the IgH locus can stratify mature PMs into groups with distinct survival probabilities.
authors: Institute of Surgical Pathology, University Zurich, Zurich, Switzerland. marianne.tinguely@usz.ch
authors: Marianne
authors: M
authors: Tinguely
authors: Bettina
authors: B
authors: Jenni
authors: Tanja
authors: T
authors: Reineke
authors: Dimitri
authors: D
authors: Korol
authors: Andreas
authors: A
authors: Kofler
authors: Valentin
authors: V
authors: Rousson
authors: Corina
authors: C
authors: Dommann-Scherrer
authors: Robert
authors: R
authors: Maurer
authors: Holger
authors: H
authors: Moch
authors: Nicole M
authors: NM
authors: Probst-Hensch
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013557:Switzerland / Q000453:epidemiology; D046888:Tissue Array Analysis; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019938:Cyclin D1