EXTRAMEDULLARY ORGAN MYELOMA MANIFESTATIONS AND SOFT TISSUE INVOLVEMENT GROWING PER CONTINUITATEM FROM BONE OSTEOLYSES IN PATIENTS WITH MULTIPLE MYELOMA SHOW SIMILAR INCIDENCES OF TP53 DELETION

• Published in: Anticancer research Vol. 31; no. 5; p. 1963
• Main Authors: Billecke, L, Murga Penas, EM, May, A M, Engelhardt, M, Nagler, A, Leiba, M, Schiby, G, Kroeger, N, Zustin, J, Marx, A, Matschke, J, Tiemann, M, Goekkurt, E, Bokemeyer, C, Schilling, G
• Format: Journal Article
• Language: English
• Published: 01.05.2011
• ISSN: 0250-7005

Extramedullary (EM) organ impairment is a rare and late event in the course of multiple myeloma (MM) disease. It is associated with a very rapid clinical progression and an unfavourable outcome, due to refractoriness to chemotherapy. Recent studies suggest a correlation between the clinical course of patients with EM organ impairment and specific genetic aberrations, especially deletion of the tumor suppressor gene TP53 on 17p13. In this context one FISH study of 9 MM patients reported that the incidence of TP53 deletions in the bone marrow of MM patients with central nervous system (CNS) involvement was about 75% higher than in the MM patient without CNS involvement. However, there is a lack of genetic data for extramedullary manifestations. Methods: We herein report the first cytogenetic investigation of diverse EM-organ manifestations with a new technique of clg-FISH on paraffin sections, developed in our laboratory. We analysed 17 MM patients with EM-organ impairment and 14 MM patients with bone or soft tissue involvement originating from bone lesions (control group). Extramedullary organ involvements comprised biopsies from skin, pleura, pleural effusion, uterus, liver, CNS, subcutaneous soft tissue, lymph node and thyroid gland, attained at different stages of the disease. The second group consisted of bone lesions or surrounding soft tissue, like muscle, which was infiltrated per continuitatem, which is frequently seen already at initial diagnosis. We compared the incidences of aberrations of the most important prognostic chromosomal regions in MM. Results and Discussion: We showed a deletion of TP53 in 29% vs. 21%, c-mycoverrepresentation in 25% vs. 29%, deletion of 13q14 in 25% vs. 29% and translocation t(4; 14) in 41% vs. 23%. Interestingly, this is in contrast to detection of a higher incidence of TP53 deletions in MM patients with CNS-involvement, supporting the hypothesis described above. Further investigations on a larger patient cohort are needed to prove our surprising findings.