BackgroundEnhancer of zest homolog 2 (EZH2), a histone 3 methyltransferase, is associated with aggressive behavior of many tumors and is a promising target of molecular therapy.MethodsTo better elucidate the relevance of EZH2 in breast cancer subtypes, we evaluated EZH2 expression in 226 invasive breast carcinomas with four distinct immunophenotypes and in association with clinicopathological features.ResultsOf these cases, 138 (61.1 %) were defined as EZH2-overexpressing with a multiplicative score > 3. EZH2 expression was inversely related to the status of ER and PR (Chi-square, p < 0.001), and it was significantly associated with HER2 positivity, high proliferative index, and high histologic grade (Chi-square, p < 0.05). ER-positive breast carcinoma with low proliferative index (Ki67 < 14 %) showed the lowest expression and triple-negative breast carcinoma showed the highest overexpression of EZH2, 18.5 % (10/54) versus 90.9 % (50/55) (Chi-square, p < 0.001). Intriguingly, 88 % (44/50) cases of grade 3 triple-negative breast carcinoma showed uniformly strong EZH2 expression with a multiplicative score of 9. The percentage of EZH2 overexpression in ER-positive breast carcinoma with a high proliferative index or HER2-positive cases were 61.2 and 74 %, respectively. Furthermore, EZH2 expression was significantly elevated in high-grade DCIS compared to benign lesions (90 % versus 0, p < 0.001). However, there is no association between EZH2 expression and the status of histone 3 lysine 27 trimethylation or other clinicopathologic features.ConclusionIn summary, triple-negative breast carcinoma showed the highest overexpression of EZH2. EZH2 overexpression is associated aggressive pathologic features including high nuclear grade, high proliferative index, and positivity of HER2 of breast carcinoma.
Plants of the genus Kobresia are alpine grass species of high ecological and economic importance. Vegetative growth is the dominant means of reproduction for the Kobresia. Studies suggest that substantial vegetative growth can reduce genetic diversity and renders populations less able to buffer changing and extreme conditions. Kobresia are dominant species in the Qinghai-Tibet plateau in China where they face harsh conditions and frequent disturbance. The genetic diversity of five Kobresia species (K. humilis, K. royleana, K. kansuensis , K. tibetica and K. setchwanensis) from the Qinghai-Tibet plateau was assessed. The results reveal high genetic diversity at the population level for all of the species and there does not appear to be a relationship between altitude and genetic diversity. AMOVA analysis shows that most genetic variability resides among individuals within populations, whereas only a minor portion is found among populations. Of the five species, K. royleana and K. kansuensis have the highest levels of gene flow and the lowest genetic differentiation. While K. setchwanensis has the lowest gene flow and the greatest genetic differentiation. The level of gene flow between populations and the mating system play a critical role in the genetic structure of these Kobresia populations. Despite the predominance of vegetative growth enough sexual reproduction occurs to maintain the relatively high genetic diversity in Kobresia populations.
Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands Aims: Pleomorphic adenoma (PA) of the breast, and especially its malignant transformation, is extremely rare and represents a diagnostic pitfall. Molecular alterations in this entity have not been investigated. We aimed to examine the clinicopathological features of our breast PAs and perform molecular analysis. Methods and results: Seven cases of breast PA, including two cases of carcinoma ex PA, were analysed. PLAG1 and HMGA2 gene rearrangements were assayed by fluorescence in-situ hybridisation (FISH) and RNA sequencing (RNA-Seq), respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to verify RNA sequencing results. All seven cases of breast PA occurred in women. The histological features were similar to the analogous tumour in salivary glands, including a dual epithelial-myoepithelial component and negativity of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry. Of the two cases with carcinoma ex PA, one demonstrated minimal invasion and one was extensively invasive. PLAG1 rearrangements were identified in two cases (28.6%), but no rearrangements of HMG2A were found. A novel fusion product in PAs, TRPS1-PLAG1, was identified in one case. No patients had recurrence or metastasis with a follow-up period of 6-158 months. Conclusions: Breast PA is rare, but it is an important differential diagnosis of breast pathology with the potential to develop carcinoma ex PA. We report a novel TRPS1-PLAG1 fusion gene in breast PA.
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