Identification of a proliferation signature related to survival in nodal peripheral T-cell lymphomas.
OBJECTIVE
Nodal peripheral T-cell lymphomas (PTCLs) constitute a heterogeneous group of neoplasms, suggesting the existence of molecular differences contributing to their histologic and clinical variability. Initial expression profiling studies of T-cell lymphomas have been inconclusive in yielding clinically relevant insights. We applied DNA microarrays to gain insight into the molecular signatures associated with prognosis.


METHODS
We analyzed the expression profiles of 35 nodal PTCLs (23 PTCLs unspecified and 12 angioimmunoblastic) using two different microarray platforms, the cDNA microarray developed at the Spanish National Cancer Centre and an oligonucleotide microarray.


RESULTS
We identified five clusters of genes, the expression of which varied significantly among the samples. Genes in these clusters seemed to be functionally related to different cellular processes such as proliferation, inflammatory response, and T-cell or B-cell lineages. Regardless of the microarray platform used, overexpression of genes in the proliferation signature was associated significantly with shorter survival of patients. This proliferation signature included genes commonly associated with the cell cycle, such as CCNA, CCNB, TOP2A, and PCNA. Moreover the PTCL proliferation signature showed a statistically significant inverse correlation with clusters of the inflammatory response (P < .0001), as well as with the percentage of CD68(+) cells.


CONCLUSIONS
Our findings indicate that proliferation could be an important factor in evaluating nodal PTCL outcome and may help to define a more aggressive phenotype.
Cuadros
Marta
M
Human Genetics Group and Genotyping Unit, Human Cancer Genetics Program, Spanish National Cancer Centre, Madrid, Spain.
Dave
Sandeep S
SS
Jaffe
Elaine S
ES
Honrado
Emiliano
E
Milne
Roger
R
Alves
Javier
J
Rodríguez
Jose
J
Zajac
Magdalena
M
Benitez
Javier
J
Staudt
Louis M
LM
Martinez-Delgado
Beatriz
B
D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000145:classification / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D016019:Survival Analysis