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The current World Health Organization classification considers myelodysplastic syndrome with isolated del(5q) a distinct entity owing to its characteristic clinical and pathologic features. Recently, several studies have examined survival, leukemic transformation, and various prognostic factors in these patients. However, there is a lack of detailed comparative pathologic analysis of myelodysplastic syndrome cases in which del(5q) is present in association with additional cytogenetic abnormalities. We studied 26 cases of myelodysplastic syndrome at initial diagnosis with 5q- alone, 5q- plus 1 additional abnormality, and 5q- as part of a complex karyotype. Four of 17 patients had evidence of JAK2 V617F mutation. In contrast to cases of myelodysplastic syndrome with isolated 5q-, patients with additional abnormalities had normal mean corpuscular volume and decreased platelet counts (P < .001). Based on bone marrow examination, they were significantly more likely to have increased cellularity, trilineage dysplasia, lower proportion of small hypolobated megakaryocytes, higher number of blasts, and fibrosis. The presence of these morphologic features can be used to distinguish these more aggressive cases from those with myelodysplastic syndrome with isolated 5q- and a more benign clinical course. [ABSTRACT FROM AUTHOR]

Background & Aims: The peroxisome proliferator-activated receptor γ (PPARG, PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. There is controversy over the pro-oncogenic or antioncogenic effects of PPARG, and little is known about its prognostic significance in colon cancer. Methods: Among 470 patients with colorectal cancer (stages I–IV) identified in 2 independent prospective cohorts, PPARG expression was detected in 102 tumors (22%) by immunohistochemistry. Cox proportional hazards models were used to compute hazard ratios (HRs) of colorectal cancer–specific and overall mortalities, adjusted for patient characteristics and molecular features including cyclooxygenase 2, fatty acid synthase, KRAS, BRAF, PIK3CA, p53, p21, β-catenin, LINE-1 hypomethylation, microsatellite instability (MSI), and the CpG island methylation phenotype (CIMP). Results: Compared with patients with PPARG-negative tumors, patients with PPARG-positive tumors had significantly lower overall mortality, determined by Kaplan–Meier analysis (P = .0047), univariate Cox regression (HR, 0.55; 95% confidence interval [CI], 0.37–0.84; P = .0053), and multivariate analysis (adjusted HR, 0.43; 95% CI, 0.27–0.69; P = .0004). Patients with PPARG-positive tumors experienced lower colorectal cancer–specific mortality (adjusted HR, 0.44; 95% CI, 0.25–0.79; P = .0054). The relationship between PPARG and lower mortality did not appear to be significantly modified by MSI, CIMP, LINE-1, or the other clinical and molecular variables examined (all P interaction > .05). Conclusions: Tumor expression of PPARG is independently associated with longer survival of patients. PPARG expression appears to mark an indolent subset of colorectal cancers. [Copyright &y& Elsevier]

Abstract: In a series of 105 patients with polycythemia vera, we retrospectively determined whether the JAK2 V617F mutation correlated with severity of disease phenotype. Higher JAK2 V617F allele burden correlated with more advanced myelofibrosis, greater splenomegaly, and higher white blood cell count, but not with age, gender, hematocrit level, or frequency of phlebotomy prior to cytoreductive therapy. Although a subgroup at increased risk for thrombosis was not clearly defined, there was a suggestion that frequency of thrombosis increased as the JAK2 V617F allele burden increased. The JAK2 V617F allele burden did not change significantly in treated patients with serial JAK2 analyses. [ABSTRACT FROM AUTHOR]