Recent identification of somatic MED12 mutations in most uterine leiomyomas brings a new venue for the study of the tumorigenesis of leiomyomas. We are particularly interested in the correlation of MED12 and HMGA2 gene products in leiomyomas and leiomyosarcomas with and without MED12 mutations. To address these issues, in this study we examined MED12 mutations in a large cohort of usual type leiomyomas (178 cases) and uterine leiomyosarcomas (32 cases). We found that 74.7% (133/178) of leiomyomas had MED12 mutations, which was consistent with several independent studies. In contrast, only 9.7% (3/32) of leiomyosarcomas harbored MED12 mutations. Expression analysis by Western blot and immunohistochemistry revealed that those leiomyomas with complex MED12 mutations had significantly lower protein products than matched myometrium. Interestingly, most leiomyosarcomas without MED12 mutations also had very low levels of MED12 expression in comparison to the matched myometrium. These findings suggest a potential functional role of MED12 in both benign and malignant uterine smooth muscle tumors. When we further examined HMGA2 expression in all leiomyomas and leiomyosarcomas, we found HMGA2 overexpression was exclusively present in those leiomyomas with no MED12 mutation, accounting for 10.1 % (18/178) of total leiomyomas and 40 % (18/45) of non-MED12 mutant leiomyomas. Twenty-five % (8/32) of leiomyosarcomas had HMGA2 overexpression and no MED12 mutations were found in HMGA2 positive leiomyosarcoma. These findings strongly suggest that MED12 mutations and HMGA2 overexpression are independent genetic events that occur in leiomyomas, and they may act differently in the tumorigenesis of uterine leiomyomas.

When applied, the PD has a stronger correlation to the SD, particularly when the biopsies are from the lower urinary tract. Further study with more cases is required to support this significant association.

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It is well established that the combined del(1)(p36) and del(19)(q13) is a positive prognostic molecular event in oligodendroglial tumors. However, very little is known about the frequency or impact of polysomy status for chromosomes 1/19. We examined 84consecutive pure oligodendrogliomas (68 World Health Organization [WHO] grade II and 16 WHO grade III) and analyzed them for del(1)(p36) and del(19)(q13) by fluorescent in situ hybridization. Polysomy status was recorded with accompanying deletion status, WHO grade, recurrence-free survival, and overall survival. Codeletion of 1p/19q was detected in 48% of cases and correlated with superior patient survival (p < 0.01), as expected. Of 84 cases, 36 (43%) showed polysomy of chromosome 1, 30 (36%) demonstrated polysomy of chromosome 19, and 28 (33%) had copolysomies of chromosomes 1/19. The presence of polysomy of either/or both chromosomes, regardless of deletion status, correlated with younger patient age at initial diagnosis (p < 0.01). Combined polysomy was associated with higher histologic tumor grade (p = 0.04) and conferred poor survival likelihood (p = 0.03). We conclude that polysomy of 1 and/or 19 is a relatively frequent occurrence in oligodendrogliomas and usually confers an unfavorable outcome.

Context.-Metastatic breast cancer to the central nervous system (CNS) is second only to lung cancer metastasis to the CNS in frequency. Patients with triple-negative primary breast cancer and those with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer are at an increased risk for metastasis. Very little is known about predictive or prognostic variables once patients develop CNS metastases. Currently, therapeutic options are limited, with surgery generally offered primarily to those with solitary lesions.Objectives.-To determine the influence of molecular subtypes of metastatic breast cancer on survival from the time of CNS metastasis and to aid in the prognostic stratification of these patients.Design.-We identified 59 cases of metastatic breast cancer to the CNS and analyzed them for various demographic and clinicopathologic parameters. Tumors were categorized into molecular subtypes using immunohistochemical methods: luminal A [estrogen receptor, and triple-negative. Survival after CNS metastasis for each group was plotted using a KaplanMeier curve, and multivariate analysis was performed.Results.-Patients with metastases from luminal tumors had a statistically significant survival advantage when compared with those of the triple-negative phenotype. Importantly, survival among patients with luminal A and luminal B tumors was not significantly different. Similarly, patient's age, histologic grade, and number of lesions did not contribute to determining outcomes.Conclusions.-Estrogen receptor positivity (ie, luminal phenotype) of tumors appears to determine outcomes after development of metastases. In contrast, proliferation rate had little or no effect on the long-term survival. Understanding the biology of metastases can help stratify patients into prognostically meaningful categories and tailor treatment regimens for individual patients.