Departments of 1 Internal Medicine, 2 Oncology; 3 Pathology, National Taiwan University Hospital, Taipei, Taiwan
*Correspondence to: Dr H.-F. Tien, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. Tel: +886-2-23123456; Fax: +886-2-23959583;Email: hftd{at}ha.mc.ntu.edu.tw
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Abstract |
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Patients and methods: We analyzed the chromosomal abnormalities of 200 adult patients with NHL in Taiwan and correlated the non-random aberrations with the histological subtypes.
Results: One hundred and thirty-eight patients (69%) had B-cell lymphoma. The incidence of the t(14;18) in total lymphoma was lower in Taiwan (12%) than in the West (2030%), but its incidence in follicular lymphoma was comparable between the two areas (17 of 28 patients, 61% versus 5060%). Sixty-two patients (31%) had T-cell lymphoma, including 11 angiocentric T/natural killer (NK)-cell lymphoma and only two angioimmunoblastic T-cell lymphoma (AILD). The recurrent chromosomal abnormalities in T-cell lymphoma comprised 6q deletion (30%), 11q deletion (20%), 17p deletion (16%), 17 (16%), Y (14%) and + 8 (11%). Angiocentric T/NK-cell lymphoma had a significantly higher frequency of 1q duplication (P=0.001), 6p duplication (P <0.001) and 11q deletion (P=0.011) than other T-cell lymphoma. The incidences of +3 and +5, two common abnormalities in AILD, were quite low in T-cell lymphoma in Taiwan (4% and 2%, respectively), compared with those in the West (1632% and
15%, respectively). The 11q deletion, not a common aberration in T-cell lymphoma in western countries, occurred quite frequently in Taiwan.
Conclusions: The chromosomal aberrations of NHL are quite different among various geographical areas, which may reflect the differences in the distribution of the histological subtypes of lymphoma among various areas.
Key words: chromosomal abnormalities, non-Hodgkin's lymphoma, T-cell lymphoma
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Introduction |
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In this study, we analyzed the cytogenetic abnormalities in 200 consecutive Chinese patients with NHL in Taiwan. We found that though the incidence of the chromosomal abnormality t(14;18) among all NHL is lower in this area than in western countries (12% versus 2030%), the frequency of t(14;18) in follicular lymphoma in Taiwan is comparable with that in the West (61% versus 5060%). In addition, some geographical differences in the chromosomal aberrations in T-cell lymphoma were found which might reflect the difference in the distribution of the histopathological subtypes between this area and the West.
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Patients and methods |
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Statistics
The cytogenetic findings in different groups of patients were compared with Fisher's test. The survival curves were plotted using the KaplanMeier method; differences between curves were analyzed by the log-rank test. All statistical analyses were performed using the SPSS 8.0 for Windows (SPSS, Chicago, IL, USA). P <0.05 means a significant difference.
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Results |
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Cytogenetic results of T-cell NHL and their correlation with histopathological subtypes and clinical outcomes
Sixty-two patients (31%) were diagnosed as having T-cell lymphoma. The distribution of the histopathological subtypes is shown in Table 1. Eleven patients had nasal (six patients) or nasal-type (five patients) angiocentric T/NK-cell lymphoma, nine had adult T-cell lymphoma/leukemia (ATLL) and only two had angioimmunoblastic T-cell lymphoma (AILD). Fifty patients (81%) had clonal chromosomal abnormalities; 27 of them showed complex changes with more than four abnormalities. The modal chromosome number ranged from 40 to 96, most commonly pseudodiploidy (20 patients) and hyperdiploidy between 47 and 50 (12 patients). The distribution of chromosome gain and loss among the 44 patients with near- or pseudodiploidy is shown in Figure 1
. The most common recurrent numerical aberrations were monosomy 17 (16%), Y (14%), trisomy 8 (11%), trisomy 7 (9%), 6 (9%), X (9%) and monosomy 13 (7%). Trisomy 3 and 5 were demonstrated in only two and one case, respectively. The distribution of the structural chromosomal abnormalities among the 50 patients with clonal abnormalities is shown in Figure 2
. Deletion of the chromosome 6q was found in 15 patients (30%, Table 3
), most commonly involving 6q2125 (12 patients). Other structural aberrations included 11q deletion (20%), 17p deletion (16%), 1q duplication (14%), 1p deletion (14%), 4q deletion (10%), 9q deletion (10%) and 6p duplication (8%) (Table 3
). Duplication of 8q was found in three patients and deletion of 13q in none.
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All 11 patients with angiocentric nasal or nasal-type T/NK-cell lymphoma had clonal chromosomal aberrations. Six had complex changes with more than four abnormalities and two, three abnormalities. The non-random abnormalities included isochromosome of 7q (two patients), duplication of 1q (five patients, two with isochromosome of 1q and three with unbalanced translocation of duplicated segment distal to 1q21 to other chromosomes), deletion of 6q (four patients), and deletion of 11q23 (five patients, with 11q2325 involvement in four of them). Three patients, all having nasal lesions, showed duplication of 6p; two presented as i(6) (p10) and one, der(6) t(6;6) (q23;p11). Compared with other subtypes of T-cell lymphoma, the patients with angiocentric T/NK-cell lymphoma had a significantly higher frequency of 1q duplication (45% versus 4%, P=0.001), 6p duplication (27% versus 2%, P <0.001) and 11q deletion (45% versus 10%, P=0.011) than others (Table 3). Nine patients had adult T-cell leukemia/lymphoma (ATLL) and positive serologic tests for human T-cell leukemia virus type I (HTLV-1). Five patients had complex chromosomal changes with more than four abnormalities and two patients, three abnormalities. There were no specific aberrations.
The median overall survival in the patients with T-cell lymphoma was 10 months (range 1172 months). There was no prognostic implication of the most common recurrent chromosomal aberrations, including deletion of 6q, 17p deletion/monosomy 17, deletion of 11q, duplication of 1q and deletion of 1p.
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Discussion |
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In this study, 62 patients (31%) had T-cell lymphoma, an incidence similar to those reported previously in Asia [4], but much higher than in western countries (
10%) [21
]. The frequency of AILD in T-cell lymphoma was lower and that of ATLL and angiocentric T/NK-cell lymphoma was higher in this area (Table 1
) than in the West [21
]. It is not easy to compare the chromosomal abnormalities of T-cell lymphoma among different geographical areas because the reports are few and various histological classifications were used [13
, 14
, 22
]. In this study, the patients with T-cell lymphoma had low incidences of trisomy 3 and trisomy 5 [two patients (4%) and one patient (2%), respectively], compared with those in the West (1632% and
15%, respectively) [13
, 14
, 23
]. These two numerical abnormalities are closely correlated with AILD [13
], a subtype of T-cell lymphoma very common in western countries [14
, 21
], but rare in Taiwan. Trisomy 3 has also been detected frequently in ATLL patients in endemic areas; however, only one of the nine patients with ATLL in this area, a non-endemic area, showed this change. None of the three NHL patients with antibody to ATLL-associated antigen in Saitama, a non-endemic area, had trisomy 3, either [24
].
On the other hand, 10 patients (16%) with T-cell lymphoma in this study had deletion of 11q, which was an uncommon structural aberration of T-cell lymphoma in previous reports [13, 23
]. This chromosomal aberration is also rare in B-cell lymphoma other than small lymphocytic lymphoma [25
]. It was only found in seven (5%) of 138 patients with B-cell lymphoma in this study (data not shown). Interestingly, patients with angiocentric T/NK-cell lymphoma had a significantly higher incidence of 11q deletion than other subtypes of T-cell lymphoma (Table 3
). Most patients with this subtype of lymphoma and deletion of 11q involved 11q2325. If the finding is confirmed by further studies on a large number of patients, search for a suppressor gene in 11q2325 may be helpful for understanding the pathogenesis of angiocentric T/NK-cell lymphoma.
Duplication of 6p was found to be associated with mycosis fungoides and Sezary syndrome [13, 23
], but was uncommon in other subtypes of lymphoma [9
, 13
, 20
]. In this study, 6p duplication was highly correlated with nasal angiocentric T/NK-cell lymphoma. Three of the six patients with this subtype of lymphoma showed 6p duplication; two presented as i(6) (p10) and one of them as the sole aberration [15
]. For comparison, only one patient (2%) with other T-cell lymphoma and five patients (4%) with B-cell lymphoma (data not shown) had this change. Although the patients with T-cell lymphoma in this study had a high incidence of monosomy 17 and deletion of 17p, which was not shown in previous reports, the abnormalities did not show subtype propensity.
In summary, the incidence of follicular lymphoma is lower and T-cell lymphoma is higher in Taiwan than in the West, and among T-cell lymphoma there are fewer AILD but more angiocentric T/NK-cell lymphoma in Taiwan. Although the frequency of t(14;18) among total NHL is low in Taiwan, the occurrence of the aberration among follicular lymphoma here is similar to that in the West. In T-cell lymphoma, the incidences of trisomy 3 and trisomy 5, two common abnormalities in AILD, are quite low, but deletion of 11q, a chromosomal change significantly more frequent in angiocentric T/NK-cell lymphoma than other T-cell NHL, is high in this area, compared with western countries. These findings suggest that the geographical differences in the chromosomal aberrations of NHL reflect the differences in the distribution of histological subtypes of lymphoma among various areas. The pathogenesis of each subtype of lymphoma may be similar worldwide.
Received for publication October 25, 2003. Revision received February 11, 2004. Accepted for publication February 24, 2004.
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