Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis

<p>Abstract</p> <p>Background</p> <p>Immunohistochemical studies of lymphatic vessels have been limited by a lack of specific markers. Recently, the novel D2-40 antibody, which selectively marks endothelium of lymphatic vessels, was released. The aim of our study is to compare lymphatic and blood vessel invasion detected by hematoxylin and eosin (H&E) versus that detected by immunohistochemistry, relating them with morphologic and molecular prognostic factors.</p> <p>Methods</p> <p>We selected 123 cases of invasive mammary carcinomas stratified into three subgroups according to axillary lymph node status: macrometastases, micrometastases, and lymph node negative. Lymphatic (LVI) and blood (BVI) vessel invasion were evaluated by H&E and immunohistochemistry using the D2-40 and CD31 antibodies, and related to histologic tumor type and grade, estrogen and progesterone receptors, E-cadherin, Ki67, p53, and Her2/<it>neu </it>expression.</p> <p>Results</p> <p>LVI was detected in H&E-stained sections in 17/123 cases (13.8%), and in D2-40 sections in 35/123 cases (28.5%) (Kappa = 0.433). BVI was detected in H&E-stained sections in 5/123 cases (4.1%), and in CD31 stained sections in 19/123 cases (15.4%) (Kappa = 0.198). LVI is positively related to higher histologic grade (p = 0.013), higher Ki67 expression (p = 0.00013), and to the presence of macrometastases (p = 0.002), and inversely related to estrogen (p = 0.0016) and progesterone (p = 0.00017) receptors expression.</p> <p>Conclusion</p> <p>D2-40 is a reliable marker of lymphatic vessels and is a useful tool for lymphatic emboli identification in immunostained sections of breast carcinomas with higher identification rates than H&E. Lymphatic vessel invasion was related to other features (high combined histologic grade, high Ki67 score, negative hormone receptors expression) associated with worse prognosis, probable reflecting a potential for lymphatic metastatic spread and aggressive behavior.</p

Phosphorylation of Chromosome Core Components May Serve as Axis Marks for the Status of Chromosomal Events during Mammalian Meiosis

Meiotic recombination and chromosome synapsis between homologous chromosomes are essential for proper chromosome segregation at the first meiotic division. While recombination and synapsis, as well as checkpoints that monitor these two events, take place in the context of a prophase I-specific axial chromosome structure, it remains unclear how chromosome axis components contribute to these processes. We show here that many protein components of the meiotic chromosome axis, including SYCP2, SYCP3, HORMAD1, HORMAD2, SMC3, STAG3, and REC8, become post-translationally modified by phosphorylation during the prophase I stage. We found that HORMAD1 and SMC3 are phosphorylated at a consensus site for the ATM/ATR checkpoint kinase and that the phosphorylated forms of HORMAD1 and SMC3 localize preferentially to unsynapsed chromosomal regions where synapsis has not yet occurred, but not to synapsed or desynapsed regions. We investigated the genetic requirements for the phosphorylation events and revealed that the phosphorylation levels of HORMAD1, HORMAD2, and SMC3 are dramatically reduced in the absence of initiation of meiotic recombination, whereas BRCA1 and SYCP3 are required for normal levels of phosphorylation of HORMAD1 and HORMAD2, but not of SMC3. Interestingly, reduced HORMAD1 and HORMAD2 phosphorylation is associated with impaired targeting of the MSUC (meiotic silencing of unsynapsed chromatin) machinery to unsynapsed chromosomes, suggesting that these post-translational events contribute to the regulation of the synapsis surveillance system. We propose that modifications of chromosome axis components serve as signals that facilitate chromosomal events including recombination, checkpoint control, transcription, and synapsis regulation

Zircon from the East Orebody of the Bayan Obo Fe–Nb–REE deposit, China, and SHRIMP ages for carbonatite-related magmatism and REE mineralization events

Extremely U-depleted

Prograde and retrograde history of the Junction School eclogite, California, and an evaluation of garnet-phengite-clinopyroxene thermobarometry

Quantitative thermobarometry of inclusions in zoned garnet from a Franciscan eclogite block record a counter-clockwise P–T path from blueschist to eclogite and back. Garnet retains prograde zoning from inclusion-rich Alm52Grs30Pyp6Sps12 cores to inclusion-poor Alm62Grs25Pyp12Sps1 mantles, with overgrowths of highly variable composition. Barometry using the Waters–Martin version of the garnet–phengite–omphacite thermobarometer yields conditions of 7–15 kbar, 400–500°C (garnet cores), 18–22 kbar, ∼550°C (mantles), and 10–14 kbar, 350–450°C (overgrowths), in agreement with clinozoisite–sphene–rutile–garnet–quartz barometry. These pressures are ∼10–15 kbar less than those obtained using more recent, fully thermodynamic calibrations of the phengite–omphacite–garnet thermobarometer. Low early temperatures suggest that the block was subducted in a thermally mature subduction zone and not at the inception of subduction when prograde temperature is expected to be higher. Franciscan high-grade blocks likely represent crust subducted throughout the history of this convergent margin, rather than only at the inception of the subduction zone