Significance of CAL2 by Immunohistochemistry in Detecting CALR Mutation in Egyptian Patients with BCR- ABL Negative Myeloproliferative Neoplasms

Abstract

Background: Essential thrombocythemia (ET) with Primary Myelofibrosis (PMF) and finally Polycythaemia Vera (PV), are considered the  three main entities of the Philadelphia-negative MPNs. Mutations in JAKII, together with CALR and Myeloproliferative Leukemia Protein  (MPL) genes can be detected in most of cases with Philadelphia-negative MPNs. The discovery of CALR mutations was implicated in better  understanding of the molecular mechanisms involved in the pathogenesis of MPNs patients who had no mutations in JAKII or MPL  genes. 

Patients and methods: The current study included 56 participants diagnosed with MPNs. Bone marrow trephine biopsy  (BMB) was the sample of choice in our study. CALR specific monoclonal antibody (CAL2) by IHC was done for all MPN patients on BMB  specimens. 

Results: Nearly 82 % of our cases (46/56) were positive for CALR mutation by IHC with sensitivity of 96.4%, and specificity of  88.9%, with positive predictive value of 94.7%, while negative predictive value was 92.3%, and total accuracy of CALR was 93.9%. We found  a significant association between JAKII mutation and CALR positive patients (p=0.004) hyper cellular marrow was prevailing in CALR  positive patients (p= 0.004). In addition, CALR mutant patients were associated significantly with higher degrees of fibrosis grade III & IV  (p= 0.044). However, no significant relation between splenomegaly and CALR positivity was detected in our study. 

Conclusion: CAL2 by  IHC was a sensitive and specific marker in detecting CALR mutation in patients diagnosed as MPN. Moreover, it was readily available and  cost effective than other routine molecular techniques used in detecting such mutation