Evaluation of chromosomal abnormalities by cIg-FISH and association with proliferative and apoptotic indexes in multiple myeloma

Abstract

Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

Genetic aberrations in multiple myeloma characterized by cIg-FISH: a Brazilian context

“…In the present study, the frequencies of t(11;14), t(4;14) and del(13q) were in agreement with previous studies ( 3 , 11 12 13 14 ), whereas t(14;16) and del(17p) were observed in lower frequencies than in other series ( 3 , 11 , 15 ). In a previous study from Brazil ( 15 ), the frequencies of t(11;14), del(13q) and del(17p) were similar to the ones herein reported, while a higher frequency of t(4;14) was found in our study (14.1% vs 9.3% in the mentioned study) ( 15 ). The frequency of t(14;16) has not yet been reported for Brazilian patients.…”

Validation of interphase fluorescence in situ hybridization (iFISH) for multiple myeloma using CD138 positive cells

“… 15 This technique, which also requires a long time for training and does not have good reproducibility, was used in two Brazilian studies. 18 , 19 The third approach is by selecting cells either by flow cytometry or immunomagnetic bead-based PC sorting. 4 …”

“…1q amplification, t(4;14), t(14;16) and 17p13 deletion are associated with bad prognoses, 4 , 8 , 12 , 21 and the 13q deletion is still controversial. 18 In particular, t(4;14)(p16;q32) at diagnosis has been shown as a bad prognostic marker, 18 even in smoldering MM 22 , 23 and in patients with symptomatic MM treated with conventional chemotherapy, which may be ameliorated with bortezomib-based combinations. 2 …”

Clinical and epidemiological features of multiple myeloma patients from a low socio-economic region of Brazil

“…In the southern regions of Brazil, where genetic alterations have been studied in MM, no such bias was described. 7 …”