Clinicopathological and molecular markers associated with prognosis and treatment effectiveness of endometrial stromal sarcoma: a retrospective study in China

PURPOSE: To evaluate the clinicopathological and immunophenotypic characteristics of endometrial stromal sarcoma (ESS) in China. METHODS AND MATERIALS: Seventy-two consecutive ESS cases treated between 1995 and 2009 were retrospectively reviewed. RESULTS: Sixty-three patients received surgical treatment. Forty-one patients underwent pelvic lymphadenectomy. In paraffin-embedded specimens, expression of the following molecular markers was detected: CD10 (27/36), vimentin (37/38), HHF35 (3/32), S-100 (0/25), desmin (2/29), CD117 (0/23), CD34 (2/24), alpha-inhibin (0/17), CK (1/34), CD99 (4/9), smooth muscle actin (5/25), EMA (0/7), estrogen receptor (13/16) and progesterone receptor (13/16). CD10 and vimentin were expressed more frequently in these specimens. Tumor classification, CD10 and surgical procedures were significantly associated with disease-free survival (DFS). Surgical procedures were significantly associated with overall survival (OS). Tumor stage (P = 0.024) and surgical procedure (P = 0.042) were found to be significant independent prognostic factors for DFS. No complete or partial response was observed among patients who received radiotherapy or chemotherapy. CONCLUSIONS: Our results indicate that total hysterectomy with bilateral salpingo-oophorectomy followed by pelvic lymphadenectomy is associated with an improved treatment outcome. CD10-negative expression may contribute to the malignant characteristics and recurrence associated with ESS

Negative flat band magnetism in a spin-orbit coupled correlated kagome magnet

It has long been speculated that electronic flat band systems can be a fertile ground for hosting novel emergent phenomena including unconventional magnetism and superconductivity. Although flat bands are known to exist in a few systems such as heavy fermion materials and twisted bilayer graphene, their microscopic roles and underlying mechanisms in generating emergent behavior remain elusive. Here we use scanning tunneling microscopy to elucidate the atomically resolved electronic states and their magnetic response in the kagome magnet Co3Sn2S2. We observe a pronounced peak at the Fermi level, which is identified to arise from the kinetically frustrated kagome flat band. Increasing magnetic field up to +-8T, this state exhibits an anomalous magnetization-polarized Zeeman shift, dominated by an orbital moment in opposite to the field direction. Such negative magnetism can be understood as spin-orbit coupling induced quantum phase effects tied to non-trivial flat band systems. We image the flat band peak, resolve the associated negative magnetism, and provide its connection to the Berry curvature field, showing that Co3Sn2S2 is a rare example of kagome magnet where the low energy physics can be dominated by the spin-orbit coupled flat band. Our methodology of probing band-resolved ordering phenomena such as spin-orbit magnetism can also be applied in future experiments to elucidate other exotic phenomena including flat band superconductivity and anomalous quantum transport.Comment: Nature Physics onlin

Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility.

Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation

Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others. By contrast, the majority of truncal and clonal driver mutations occurred in tumor-suppressor genes, including TP53, KMT2D and ZNF750, among others. Interestingly, phyloepigenetic trees robustly recapitulated the topological structures of the phylogenetic trees, indicating a possible relationship between genetic and epigenetic alterations. Our integrated investigations of spatial ITH and clonal evolution provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ESCC