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Sequential analysis of 43 patients with non-Hodgkin's lymphoma: clinical
correlations with cytogenetic, histologic, immunophenotyping, and molecular
studies
J Whang-Peng, T Knutsen, ES Jaffe, SM Steinberg, M Raffeld, WP Zhao, P Duffey, K Condron, T Yano and DL Longo
Medicine Branch, National Cancer Institute, National Institutes of Health,
Bethesda, MD 20892.
Few reports correlating specific cytogenetic abnormalities with distinct
subtypes of lymphoma have performed serial studies at diagnosis and at
tumor recurrence or progression. In our file of 325 cytogenetically
analyzed non-Hodgkin's lymphoma (NHL) patients studied over the past
decade, 43 had serial biopsies, 39 of whom had at least two successful
preparations; of the 43, nine had one and 32 had two or more
cytogenetically abnormal specimens. In this study, we correlated
cytogenetic, histopathologic, molecular, and clinical parameters. Patients
with low-grade lymphomas were as likely as patients with intermediate- or
high-grade lymphomas to acquire new chromosomal abnormalities with time (16
of 23 patients as compared with 7 of 16; P2 = .11, chi 2 test). In four
patients, originally diagnosed indolent disease progressed to aggressive
disease; all had t(14;18), all gained additional chromosomal abnormalities
with disease progression, and three of the four expressed abnormalities
associated with disease progression and/or short survival: der(18), +7,
and/or +12. Cytogenetic results from early disease were compared with those
obtained later in disease: in the t(14;18) group, the most common
abnormalities were +7 (eight patients) and der(18) (five patients), both
seen later in disease. The most common abnormalities in patients without
t(14;18) were 6q deletions; they were seen in both early and late disease
and were associated with significantly shorter survivals (P2 = .0014)
compared with all patients without 6q deletions. Secondary chromosomal
abnormalities, observed after at least one previous abnormal study, were
seen in 19 of 22 t(14;18) patients and in 11 of 21 patients without
t(14;18) and were associated with a poor survival (P2 = .13) compared with
patients without any secondary chromosomal abnormalities. Chromosome 1
abnormalities were seen in almost half of the patients and were observed in
initial specimens and early in disease as well as late in disease and as
secondary abnormalities; 1q involvement was more frequent than 1p (15
versus eight patients) and was significantly associated with poor survival
only in patients with intermediate-/high- grade disease; the most common
breakpoints were 1q21-q22 (nine patients) and 1p36 (six patients).
Breakpoints at 2q21 and 3q27-q29 were limited to patients with t(14;18) and
were almost exclusively secondary in nature. Molecular studies in 24 of our
patients showed discrepancies with the cytogenetic results in only three
patients: two had t(14;18) but no molecular rearrangements while two
patients had no visible t(14;18) but were positive for major breakpoint
region (MBR) rearrangement. The presence of MBR or minor breakpoint cluster
(MCR) rearrangement had no apparent effect on survival.(ABSTRACT TRUNCATED
AT 400 WORDS)
Volume 85,
Issue 1,
pp. 203-216,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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