Prognostic significance of receptor for hyaluronan acid-mediated motility (CD168) in acute pediatric leukemias - assessment of clinical outcome, post induction, end of treatment and minimal residual disease

ABSTRACT Introduction: The extracellular matrix protein hyaluronan acid plays an active in role in tumor cell proliferation and invasion. Hyaluronan acid receptors, namely CD168 or the receptor for hyaluronan acid-mediated motility (RHAMM) and CD44 have been implicated in promoting malignancy. There is a lacuna in data on the expression of the receptor in pediatric leukemias. Methods: Pediatric patients with acute leukemia who were diagnosed, treated and followed up in our center were enrolled. The bone marrow biopsies performed prior to treatment were subjected to immunohistochemical staining (54 biopsies: acute lymphoblastic leukemia - 45, acute myeloid leukemia - 9). Blast counts were carried out at diagnosis, end of the induction phase and end of chemotherapy, the minimal residual disease was assessed and follow up details were collected. Positivity was correlated with initial blast count, post-induction blast count, minimal residual disease and patient survival. Results: There was no correlation between the initial blast count and the percentage of blasts with RHAMM expression. The positive correlation between percentage of blasts expressing RHAMM and the post-induction blast count was moderate in acute myeloid leukemia (0.74) and mild in acute lymphoblastic leukemia (0.48). There was a statistically significant difference in RHAMM expression between the two minimal residual disease risk groups (p-value = 0.012) with a negative prognostic effect of RHAMM expression. Moreover, a negative prognostic effect of RHAMM expression was noted when patient survival was considered. Conclusion: This study shows that blasts in acute myeloid leukemia show more RHAMM positivity than those of acute lymphoblastic leukemia indicating the aggressive nature of this type of leukemia. In acute leukemias, patients with high percentages of RHAMM-positive blasts had more post-induction blasts, blasts in minimal residual disease and poorer prognosis.

Characterization of Invading Glioma Cells Using Molecular Analysis of Leading-Edge Tissue

OBJECTIVE: We have introduced a method of characterization of invading glioma cells by using molecular analysis of marginal invading tumor cells and molecular profiles of glioma tumor margin. METHODS: Each of tumor core and marginal tissues was obtained in 22 glioma patients. Tumor core cells and marginal cells from each glial tumor were collected by laser capture microdissection or intraoperative microdissection under the operating microscope. Expression of MMP-2, MMP-9, CD44 and RHAMM mRNA by invading glioma cells compared with tumor core was confirmed by realtime-PCR of twenty-four glioma specimens. Clinical data also were reviewed for invasion and recurrence pattern of the gliomas radiologically and invasive rim pattern microscopically. RESULTS: Overall results of the molecular analysis showed that relative overexpression of MMP-2, MMP-9 and RHAMM were noted at the invasive edge of human glioma specimens comparing to the tumor core but CD44 was highly expressed in the tumor core comparing to the margin. High marginal expression of MMP-2 and MMP-9 were noted in poorly ill-defined margin on the pathological finding. High marginal expression of CD44 and MMP-2 were demonstrated in the midline cross group on the radiological review, and that of RHAMM and MMP-2 were showed in the aggressive recurrence group. High expression of MMP-2 seems to be involved in the various invasion-related phenomenons. CONCLUSION: Up-regulation of MMP-2, MMP-9, CD44 and RHAMM was noted in invasive edge of gliomas according to the various clinical situations.