Cyclin D1: A Prognostic Marker in Multiple Myeloma and its Association with CRP and β2-Microglobulin Level

Abstract

Introduction: Cyclin D1 is a protein encoded by the CCND1 (BCL-1) gene on chromosome 11q13 and it is an important regulator of G1 to S phase progression. Over expression of cyclin D1 protein releases cells from their normal controls when they need to exit from the cell cycle. This obstructs their maturation, and promotes transformation into a malignant phenotype. Aim: To study the role of cyclin D1 expression in trephine biopsies of multiple myeloma patients and its association with C-Reactive Protein (CRP), β2-microglobulin level and treatment response rate. Materials and Methods: This prospective observational study was conducted at Department of Pathology in collaboration with Department of Clinical Haematology, King George’s Medical University, Lucknow, India, from September 2018 to August 2019. Total 40 cases of multiple myeloma fulfilling inclusion and exclusion criteria were enrolled. Bone marrow aspiration and biopsy was done in all the cases. Immunohistochemical (IHC) expression of cyclin D1 on trephine biopsy was associated with CRP levels and β2-microglobulin expression. All investigations were repeated at six months follow-up and response was compared with expression of cyclin D1. The statistical tests applied were Chi-square test, Student t-test and paired t-test. Results: The age of cases ranged between 44 to 78 years and the mean age of the study subjects was 64.40±7.13 years. Total 67.5% of patients were males. On IHC, cyclin D1 expression was not observed in majority of cases (n=23), weak cyclin D1 expression was observed in 8 cases, while strong cyclin D1 expression was observed in 9 cases. Out of eight cases with weak cyclin D1 expression, five cases achieved partial response and two cases achieved complete response. One case was lost to follow-up. Among nine patients with strong cyclin D1 expression, six patients expired on six months follow-up and three patients achieved partial response. On comparison of two groups cyclin D1 positive and cyclin D1 negative cases it was found that cyclin D1 positive cases had an early age of onset, more than 50% plasma cells on marrow aspirate and were associated with plasmablastic morphology. Cyclin D1 positive cases also had increased CRP level as compared to cyclin D1 negative cases. Similarly, serum calcium, serum creatinine and β2-microglobulin levels were more in cyclin D1 positive group. Conclusion: Cases who have strong cyclin D1 expression at time of diagnosis showed poor response to treatment. This was also associated with increased serum CRP and β2-microglobulin levels. Hence, cyclin D1 can be used as a prognostic marker in multiple myeloma.

Keywords

• bone marrow
• c-reactive protein
• immunohistochemical expression
• trephine biopsy