C-myc Expression Of Protein And Genetic Alterations In Anaplastic Large Cell Lymphoma

Objective:To investigate the protein expression and genetic alterations of c-myc in primary systemic anaplastic large cell lymphoma(ALCL) and discuss its relationship with clinicopathologic features, immunophenotypes and prognosis.Methods:87 cases of ALCL were selected from a database of patients from 2006 to 2011 in Shanxi Tumor Hospital, and 21 cases of lymph node reactive hyperplasia specimens were taken as control.(1) Immunohistochemical method was used to detect the protein expression of c-myc, ALK, CD3, CD10, CD20, CD30, EMA and Ki-67 and to make immunophenotyping.(2) c-myc and ALK genetic alterations were detected using fluorescence in situ hybridization(Fl SH).(3) The interrelationships between protein expression, genetic alterations and clinicopathological parameters were analysed statistically.Results:(1) Immunohistochemical results: Of 87 cases, c-myc protein was expressed in 27cases(31%), ALK protein was expressed in 54 cases(62.1%). Compared with the control group, the differences were statistically significant(P <0.05); c-myc and ALK were co-expressed in 20 cases(23%); the differences of c-myc protein expression in ALK positive and ALK negative groups were statistically insignificant(P >0.05).(2) c-myc protein expression rate, c-myc and ALK co-expression rate increased with the upgrade of ALCL clinical stages, and the expression was higher in IPI(International Prognostic Index) high-risk groups than in low-risk groups(P <0.05).They were not statistically significant with patients’ gender, age, with or without B symptom, Extranodal sites and number, bone marrow infiltration.(3) FISH test results: Of 87 ALCL cases, most displayed genetic abnormality(64.4%).ALK rearrangements were most common(57.5%); c-myc rearrangement was rare; c-myc aneuploidy accounts for 21.8%.(4) The differences of c-myc aneuploidy in ALK positive and ALK negative groups were statistically insignificant(P >0.05), while they were statistically significant in c-myc groups(P <0.05) and in different International Prognostic Index(IPI) groups(P <0.05).(5) Kaplan-Meier single factor analysis: the PFS and OS of ALCL patients whose c-myc protein expression were positive and had c-myc aneuploidy were shorter than those with negative expression, and the differences were statistically significant(P <0.05).(6) Multiariable Cox Regression model parameter prognostic analysis: IPI score, ALK protein expression and c-myc aneuploidy were the risk factors affecting the survival of ALCL patients(P <0.05).Conclusion:(1) c-myc protein expression of ALCL is higher than the control group, which means it involved in the pathogenesis and progression of ALCL.(2) c-myc protein expression, genetic abnormality, the co-expression of c-myc and ALK protein and aneuploidy are related with ALCL clinical stages and International Prognostic Index, which could be used as an indicator of estimating ALCL malignant degree.(3) The IPI score, ALK protein expression and c-myc aneuploidy are risk factors affecting survival in ALCL patients, which could be used as an independent indicator of prognosis of ALCL.