In the British Journal of Cancer this week, researchers in Switzerland and the UK report that PIM kinases in diffuse large B-cell lymphoma can serve as markers of progression. The team performed immunohistochemical staining for PIM kinases and CXCR4 on tissue microarrays from 101 DLBCL patients and found that the expression of PIM1 significantly correlated with cell proliferation. "Whereas most cases exhibited cytoplasmic or cytoplasmic and nuclear PIM1 and PIM2 expression, 12 cases (10 of the non-germinal centre DLBCL type) expressed PIM1 predominately in the nucleus," the authors write. "Interestingly, nuclear expression of PIM1 significantly correlated with disease stage." These results show that PIM expression in associated with proliferation, they add, and that a "modest" response to small-molecule inhibitors shows that PIM kinases are better used as progression markers than therapeutic targets.
Also in the British Journal of Cancer this week, researchers in Europe and Canada report their independent and functional validation of a multi-tumor-type proliferation signature. The team previously demonstrated that an mRNA signature reflecting cellular proliferation had strong prognostic value. For this study, the researchers aimed to improve the marker's clinical utility. To facilitate evaluation of the signature, they devised a novel computational procedure to reduce the number of signature genes and then validated these genes in different human cancer cell lines and in a xenograft panel. "Expression of the qPCR-based signature was dramatically decreased under starvation conditions and inversely correlated with tumor volume doubling time in xenografts," the authors write. "The signature validated in breast cancer and NSCLC adenocarcinoma microarray data sets. Lastly, qPCR in a node-negative, non-adjuvantly treated breast cancer cohort showed that patients assigned to the high-proliferation group had worse disease-free survival."
Finally, in the British Journal of Cancer this week, researchers in Germany and Australia report that serum markers lactate dehydrogenase and S100B can predict disease outcome in melanoma patients with distant metastases. The team analyzed overall survival data from 855 melanoma patients with distant metastases and found that levels of serum lactate dehydrogenases and S100B as well as the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases and the number of involved distant sites were all significant independent prognostic factors of outcome. "Visceral metastases other than lung, elevated S100B, and elevated LDH had the highest negative impact on survival," the team writes. "Furthermore, complete metastasectomy had an independent favorable prognostic impact in particular for the patient subgroup with normal LDH and S100B values."