A Comparison of Bone Marrow Morphology and Peripheral Blood Findings in Low and High Level JAK2 V617F Allele Burden.

Cases with low level JAK2 V617F mutations are increasingly detected; however, the clinical interpretation of the low allele JAK2 burden may be challenging. The aim of this study is to analyze and compare the bone marrow morphology and peripheral blood findings in the low level JAK2 V617F allele burden (≤15% of JAK2) and high JAK2 V617F mutation burden patients (>15% JAK2). In total, 122 JAK2 V617F positive cases with concomitant bone marrow biopsies and peripheral blood findings were re-evaluated (62 low and 60 high level JAK2 V617F positive). Within the low burden group, normal looking megakaryocytes (p = 0.0005) were more frequently found, compared with those with no atypia (p = 0.0003), their number was more frequently not increased (p = 0.009), and they did not form clusters (p = 0.001). We found statistically significant difference in the number of platelet (p = 0.0003) and hematocrit levels (p = 0.032) when comparing the JAK2 V617F <3% and ≥3% mutation burden. In the high-level burden, the megakaryocytes were more frequently atypical (p = 0.054), and more frequently formed clusters (p = 0.053) with nuclei with maturation defects (p ≤ 0.0001). In conclusion, the JAK2 V617F mutation burden is reflected by morphological changes in the bone marrow and careful follow up of each and every patient with a low JAK2 V617F positivity is mandatory.

The expression of calpain-1 and androgen receptor in breast cancer and their correlation with clinicopathological characteristics: An immunohistochemical retrospective study.

Breast cancer is a heterogeneous disease with different biological outcome and ability to acquire resistance to therapy. The calpain family of proteases and androgen receptor (AR) are implicated in breast cancer pathogenesis and progression and are potential targets for novel treatment regimens. The aim of this study was to investigate the expression of calpain-1 and AR in breast cancer and to correlate their expression with clinicopathological variables and prognosis of patients. In this study we enrolled 219 breast cancer patients with long term follow-up information available. Immunohistochemical methods on a tissue microarray were used to investigate expression of calpain-1 and AR in tumor cells. The expression of calpain-1 and AR both differed significantly between the tumor subtypes of patients (p = 0.002 and p = 0.042 respectively). High calpain-1 expression was associated with patient's age over 50 years (p = 0.005) and positive ER status (p = 0.009), but not with other clinicopathological variables. Women with AR negative breast cancers were more likely to be older (p = 0.016), to have bigger tumors (p = 0.032), higher stage of the disease (p = 0.026), presence of exulceration (p = 0.017), negative ER status (p = 0.007) and higher Ki-67 proliferative index (p = 0.027). Calpain-1 expression was not associated with breast cancer specific overall survival in the total cohort of patients, however low calpain-1 expression was associated with adverse survival (p = 0.018) in triple negative subgroup of patients. Low calpain-1 expression was also associated with significantly shorter 5-year disease-free survival in total cohort of patients (p = 0.03). AR status was not associated with overall and disease-free survival of patients. This study has demonstrated that the expression of calpain-1 and androgen receptors are associated with important clinicopathological variables. The expression of calpain-1 was associated with improved disease-free survival of all analyzed patients and with improved overall survival of triple negative breast cancer patients.