Explore the vast range of titles available.

BackgroundAdjuvant therapy decisions may be partly based on the results of a multigene quantitative reverse transcription-polymerase chain reaction (RT-PCR)-based assay: the 21-gene recurrence score (RS) test of resection specimens. When necessary, core needle biopsy (CNB) may be considered as a surrogate. Here, we evaluated the concordance in gene expression according to results from RT-PCR-based RS testing between paired CNBs and resection specimens.MethodsCNBs and resection specimens from 50 breast cancer (BC) patients were tested to calculate RSs. First, we examined the concordance of the ER, PR and HER-2 status of tissue samples indicated by immunohistochemical (IHC) and RT-PCR analyses. Then, we compared the IHC findings of ER, PR, HER-2 and Ki-67 staining across paired samples. Ultimately, the RS and single-gene results for ER, PR, HER-2 and Ki-67 were explored between paired samples.ResultsThe concordance between IHC and RT-PCR was 100%, 80.0% and 100% for ER, PR and HER-2, respectively, in both resection specimens and CNBs. The concordance for IHC ER, PR, HER-2 and Ki-67 status was 100%, 94.0%, 52.0% and 82.0%, respectively, between paired samples. RS results from paired samples showed a strong correlation. The overall concordance in RS group classification between samples was 74%, 72% and 78% based on traditional cutoffs, TAILORx cutoffs and ASCO guidelines, respectively. ER, PR, HER-2 and Ki-67 were modestly- to- strongly correlated between paired samples according to the RT-PCR results.ConclusionA modest- to- strong correlation of ER, PR, HER-2 and Ki-67 gene expression and RS between CNBs and resection specimens was observed in the present study. The 21-gene RS test could be reliably performed on CNBs. ER, PR and HER-2 status showed remarkable concordance between the IHC and RT-PCR analyses. The concordance between paired samples was high for the IHC ER, PR and Ki-67 results and low for HER-2.

AimsHuman epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT.Methods527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers ≥6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0; group C: HER2/CEP17≥2.0 and HER2 copy numbers ≥6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups.ResultsAccording to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025).ConclusionsPatients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns.

Purpose Large B‐cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+. Methods The histopathology, immunophenotype, IRF4 status of the tumors, and clinical data were reviewed. Results Twenty‐one tumors were diagnosed as LBCL, IRF4+, which were more frequently associated with a follicular growth pattern, medium‐sized blastoid cytology, germinal center B‐cell‐like, and CD5+ phenotype, compared with IRF4− ones. While most of the patients received chemotherapy with or without radiation, eight IRF4+ patients received mere surgical resection of the tumor and exhibited excellent outcome. IRF4+ cases featured a significantly higher complete remission rate, and better survivals compared with IRF4− ones. Multivariate analysis confirmed IRF4+ correlates with a better survival. Conclusion Our work confirmed the unique clinicopathologic features of LBCL, IRF4+, and disclosed for the first time the independent favorable prognostic impact of IRF4+. These findings may further unravel the heterogeneity of LBCL occurring in youth, and aid in risk stratification and tailoring the therapeutic strategy. The rearrangement of IRF4 gene not only defines a group of LBCL with distinct clinicopathologic features, but also is of practical implications for prognosis prediction and therapeutic strategy decision.

This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.

The World Health Organization has updated their classification system for the diagnosis of gliomas, combining histological features with molecular data including isocitrate dehydrogenase 1 and codeletion of chromosomal arms 1p and 19q. 1p/19q codeletion analysis is commonly performed by fluorescence in situ hybridization (FISH). In this study, we developed a 57-gene targeted next-generation sequencing (NGS) panel including 1p/19q codeletion detection mainly to assess diagnosis and potential treatment response in melanoma, gastrointestinal stromal tumor, and glioma patients. Loss of heterozygosity analysis was performed using the NGS method on 37 formalin-fixed paraffin-embedded glioma tissues that showed 1p and/or 19q loss determined by FISH. Conventional methods were applied for the validation of some glioma-related gene mutations. In 81.1% (30 of 37) and 94.6% (35 of 37) of cases, 1p and 19q were found to be in agreement whereas concordance for 1p/19q codeletion and no 1p/19q codeletion was found in 94.7% (18 of 19) and 94.4% (17 of 18) of cases, respectively. Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of 1p/19q codeletion and mutation at the same time.

Purpose To better understand the clinicopathological characteristics and molecular alterations in different intratumoral components of colorectal cancer (CRC) with heterogeneity of mismatch repair (MMR) protein expression and microsatellite instability (MSI) status. Methods The histopathological features, MSI status, and other molecular alterations were analyzed in separately microdissected intratumoral regions and matched metastatic lymph nodes in four cases with intratumoral heterogenous MMR expression screened from 500 CRC patients, using PCR-based MSI testing, MLH1 promoter methylation, and targeted next-generation sequencing (NGS). Results High microsatellite instability (MSI-H) was identified in MLH1/PMS2-deficient regions in Cases 1 to 3 and in MSH2/MSH6-deficient regions in Case 4, while microsatellite stability (MSS) was detected in all the intratumoral regions and metastatic lymph nodes with proficient MMR expression (pMMR). Intratumoral heterogeneity of MLH1 promoter methylation and/or other common driving gene mutations of CRC, such as KRAS and PIK3CA mutations, was identified in all four CRCs. Further, three cases (75%) showed heterogeneous histomorphological features in intratumoral components and metastatic lymph nodes (Cases 1, 2, and 4), and the corresponding metastatic lymph nodes showed moderate differentiation with MSS/pMMR (Cases 2 and 3). Conclusions Intratumoral heterogeneous MSI status is highly correlated with intratumoral histomorphological heterogeneity, which is also an important clue for the intratumoral heterogeneity of drive gene mutations in CRC. Thus, it is essential to detect MMR protein expression and other gene mutations in metastases before treatment, especially for CRCs with intratumoral heterogenous MMR protein expression or heterogenous histomorphological features.

Long noncoding RNAs (lncRNAs) have been shown to play important regulatory roles in human cancer. We previously verified that the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is overexpressed in gastric cancer (GC) cells and closely correlated with cell proliferation and patient prognosis. However, whether aberrant LSINCT5 expression has an important effect on GC progression is unclear, and the potential mechanisms remain unknown. In GC, E2F1 expression is also aberrant, but the biological functions of E2F1 are controversial, and the correlation between E2F1 and lncRNAs remains unknown. Expression of LSINCT5 was analyzed in metastatic GC tissues compared with nonmetastatic tissues using quantitative real-time PCR (qRT-PCR) assays. Gain and loss of function approaches were used to investigate the biological role of LSINCT5 in GC cell migration and invasion. A computational screen of LSINCT5 promoter was conducted to search for transcription factor-binding sites. LSINCT5 promoter activities were examined by ChIP and luciferase reporter assays. qRT-PCR and western blotting assays were performed to detect the expression of multiple EMT markers in cells in which LSINCT5 was overexpressed or knocked down. An integrated quantitative analysis revealed that LSINCT5 was significantly over-expressed in metastatic GC tissues. Forced LSINCT5 expression promoted cell migration and invasion, whereas loss of LSINCT5 function decreased cell migration and invasion. Mechanistic investigations showed that LSINCT5 is a direct transcriptional target of E2F1. Moreover, LSINCT5 overexpression was found to play an important role in the epithelial-to-mesenchymal transition by regulating the expression of E-cadherin, N-cadherin, vimentin, and matrix metalloproteinase-2. These data suggest that E2F1-mediated activation of LSINCT5, a regulator of cell migration and invasion, constitute the mechanistic link between the E2F1-mediated pathway and lncRNA that regulates cell migration and invasion. Thus, LSINCT5 may be a target for new GC therapies.

The World Health Organization has updated their classification system for the diagnosis of gliomas, combining histological features with molecular data including isocitrate dehydrogenase 1 and codeletion of chromosomal arms 1p and 19q. 1p/19q codeletion analysis is commonly performed by fluorescence in situ hybridization (FISH). In this study, we developed a 57-gene targeted next-generation sequencing (NGS) panel including 1p/19q codeletion detection mainly to assess diagnosis and potential treatment response in melanoma, gastrointestinal stromal tumor, and glioma patients. Loss of heterozygosity analysis was performed using the NGS method on 37 formalin-fixed paraffinembedded glioma tissues that showed 1p and/or 19q loss determined by FISH. Conventional methods were applied for the validation of some glioma-related gene mutations. In 81.1% (30 of 37) and 94.6% (35 of 37) of cases, 1p and 19q were found to be in agreement whereas concordance for 1p/19q codeletion and no 1p/19q codeletion was found in 94.7% (18 of 19) and 94.4% (17 of 18) of cases, respectively. Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of f p/19q codeletion and mutation at the same time.

WRKY family proteins are a class of plant specific transcription factors that involve in many stress response pathways. It has been shown that one Arabidopsis WRKY protein, AtWRKY29/22, is activated by MAP kinase signaling cascade and confers resistance to both bacterial and fungal pathogens. However, little is known about the biological roles of WRKY proteins in rice. In this study, we investigated the expression patterns of rice AtWRKY29/22 homolog, OsWRKY03, under different conditions, and also its possible role involved in plant defense. Our results showed that OsWRKY03 was up-regulated by several defense signaling molecules or different treatments. Further analysis revealed that the expression of OsWRKY03 was light dependent. Transcriptional activation activity of OsWRKY03 was also demonstrated by yeast functional assay. Transient expression of OsWRKY03-GFP fusion protein in onion epidermis cells showed that OsWRKY03 was a nuclear localized protein. OsNPR1 as well as several other pathogenesis-related genes, such as OsPRlb, phenylalanine ammonia-lyase （ZB8） and peroxidase （POX22.3）, were induced in OsWRKYO3-overexpressing transgenic plants. These results indicated that OsWRKY03 is located upstream of OsNPR 1 as a transcriptional activator in salicylic acid （SA）-dependent or jasmonic acid （JA）-dependent defense signaling cascades.

Background：The injury of the triangular fibrocartilage complex （TFCC） is a common cause of ulnar-sided wrist pain.The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging （MRI） could demonstrate the detailed complex anatomy of TFCC in Chinese.Methods：Fourteen Chinese cadaveric wrists （from four men and three women;age range at death from 30 to 60 years;mean age at 46 years） and forty healthy Chinese wrists （from 20 healthy volunteers,male/female：10/10;age range from 21 to 53 years with a mean age of 32 years） in Beijing Jishuitan Hospital from March 2014 to March 2016 were included in this study.All cadavers and volunteers had magnetic resonance （MR） examination of the wrist with coronal T 1-weighted and proton density-weighted imaging with fat suppression in three planes,respectively.MR arthrography （MRAr） was performed on one of the cadaveric wrists.Subsequently,all 14 cadaveric wrists were sliced into 2 mm thick slab with band saw （six in coronal plane,four in sagittal plane,and four in axial plane）.The MRI features of normal TFCC were analyzed in these specimens and forty healthy wrists.Results：Triangular fibrocartilage,the ulnar collateral ligament,and the meniscal homolog could be best observed on images in coronal plane.The palmar and dorsal radioulnar ligaments were best evaluated in transverse plane.The ulnotriquetral and ulnolunate ligaments were best visualized in sagittal plane.The latter two structures and the volar and dorsal capsules were better demonstrated on MRAr.Conclusion：High-resolution 3T MRI is capable to show the detailed complex anatomy of the TFCC and can provide valuable information for the clinical diagnosis in Chinese.