Interphase Fluorescence in Situ Hybridization Analysis of Cytogenetic Abnormalities in Egyptian Patients with Plasma Cell Myeloma

Title: Interphase Fluorescence in Situ Hybridization Analysis of Cytogenetic Abnormalities in Egyptian Patients with Plasma Cell Myeloma

Authors: Azza E Hashem, Noha H Boshnak

DOI: http://dx.doi.org/10.18535/jmscr/v4i5.13

Abstract

Background: Cytogenetic abnormalities are ubiquitous in plasma cell myeloma representing the hallmark of the disease. These abnormalities have been used as the foundation to establish prognostic factors for accurate risk stratification in plasma cell myeloma. The present study aimed to detect the incidence 14q32 IgH rearrangements, t(11;14), t(4;14), 13q del and 17p del by Interphase Fluorescence in Situ Hybridization (iFISH) and their relation to the standard prognostic factors and patients’ outcome .

Method: Thirty one newly diagnosed Egyptian myeloma patients were tested for the expression of 14q32 IgH rearrangements by using the locus specific identifier (LSI) IGH Dual Color FISH break apart rearrangement probe, we also used the LSI IGH/CCND1 Dual Color Dual Fusion Probe for detection of t(11;14)(q13;q32), LSI IGH/FGFR3 Dual Fusion Probe for detection of t(4;14)(p16;q32), LSI D13S319 (13q14.3) probe for detection of 13q del and LSI TP53 Probe for detection of 17p del on bone marrow samples collected from the patients at diagnosis.

Results: Abnormal iFISH results were found in 21 patients (67.7%) of the 31 examined patients. Ten patients (32.3%) exhibited 14q IgH rearrangement. Both t(11;14) and t(4;14) were found in 4 patients (12.9%). 17p13 del was detected in 3 patients (9.7%) while 8 patients (25.8%) showed positive results for 13q del. There were statistical significant decrease in mean total leucocytic count (P= 0.030) and mean serum albumin level (P= 0.008) in patients showing positive genetic abnormalities detected by iFISH whereas a significant increase in β2-microglobulin level (>5.5mg/dL) (P= 0.052) and kappa light chain (P= 0.015) were found in those patients. A statistically significant lower serum calcium (<10 mg/dL) (P= 0.050) and better outcome (P= 0.012) were detected in patients with positive t(11;14) while patients who didn't exhibit t(11:14) had higher serum lactate dehydrogenase (LDH) levels (>300 IU/L) (P= 0.003). Patients with positive t(4;14) had significantly older age (over 60 years) (P= 0.018) and lower platelet counts (<150x10⁹/L) (P=0.030). There was statistical significant decrease found in patients with positive t(4;14) as regards to mean of each of calcium (P= 0.020), LDH (P= 0.007) and blood urea nitrogen (BUN) serum levels (P= 0.047). A strong association has been detected between positive 17p13 del and high mean value of β2-microglobulin serum level (P= 0.000). Patients who lacked 17p13 del had significantly higher total leucocytic count (>4x10⁹/L) (P= 0.002). Patients with positive 13q del had significantly lower mean albumin level (P= 0.022) and poor outcome (P= 0.005).

Conclusion: Genetic abnormalities in patients with plasma cell myeloma are important risk factors in terms of outcome. Patients with positive t(11;14) exhibit a better outcome while patients with positive 13q del had poor outcome. 14q IgH rearrangements was the most common genetic abnormality detected however it wasn't associated with any of the standard prognostic factors.

Keywords: Plasma Cell Myeloma, Fluorescence in Situ Hybridization, Cytogenetic Abnormalities.

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Corresponding Author

Noha H Boshnak

MD, Lecturer of Clinical Pathology, Faculty of Medicine

Ain Shams University, Cairo, Egypt

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