Nuclear Mitosis Research Articles

From Trypomastigotes to Trypomastigotes: Analyzing the One-Way Intracellular Journey of Trypanosoma cruzi by Ultrastructure Expansion Microscopy.

The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, also called American trypanosomiasis. This neglected tropical disease affects millions of individuals across the Americas. To complete its life cycle, T. cruzi parasitizes both vertebrate hosts and its vector, commonly known as the 'kissing bug'. The parasite's survival and proliferation strategies are driven by the diverse environments it encounters. Despite being described by Carlos Chagas in 1909, significant knowledge gaps persist regarding the parasite's various life forms and adaptive capabilities in response to environmental cues. In this study, we employed Ultrastructure Expansion Microscopy to explore the intricate journey of T. cruzi within the host cell. Upon entry into the host cell, trypomastigotes undergo folding, resulting in intermediate forms characterized by a rounded cell body, anterior positioning of basal bodies, and a shortened flagellum. The repositioning of basal bodies and the kinetoplast and the shortening of the flagella mark the culmination of intracellular amastigogenesis. Furthermore, we analyzed intracellular trypomastigogenesis, identifying discrete intermediate forms, including leaf-shaped stages and epimastigote-like forms, which suggests a complex differentiation process. Notably, we did not observe any dividing intracellular epimastigotes, indicating that these may be non-replicative forms within the host cell. Our detailed examination of amastigote cell division revealed semi-closed nuclear mitosis, with mitotic spindle formation independent of basal bodies. This study provides new insights into the morphological and cytoskeletal changes during the intracellular stages of T. cruzi, providing a model for understanding the dynamics of intracellular amastigogenesis and trypomastigogenesis.

Exploring the biological basis of CT imaging features in pancreatic neuroendocrine tumors: a two-center study

Objective. Medical imaging offered a non-invasive window to visualize tumors, with radiomics transforming these images into quantitative data for tumor phenotyping. However, the intricate web linking imaging features, clinical endpoints, and tumor biology was mostly uncharted. This study aimed to unravel the connections between CT imaging features and clinical characteristics, including tumor histopathological grading, clinical stage, and endocrine symptoms, alongside immunohistochemical markers of tumor cell growth, such as the Ki-67 index and nuclear mitosis rate. Approach. We conducted a retrospective analysis of data from 137 patients with pancreatic neuroendocrine tumors who had undergone contrast-enhanced CT scans across two institutions. Our study focused on three clinical factors: pathological grade, clinical stage, and endocrine symptom status, in addition to two immunohistochemical markers: the Ki-67 index and the rate of nuclear mitosis. We computed both predefined (2D and 3D) and learning-based features (via sparse autoencoder, or SAE) from the scans. To unearth the relationships between imaging features, clinical factors, and immunohistochemical markers, we employed the Spearman rank correlation along with the Benjamini-Hochberg method. Furthermore, we developed and validated radiomics signatures to foresee these clinical factors. Main results. The 3D imaging features showed the strongest relationships with clinical factors and immunohistochemical markers. For the association with pathological grade, the mean absolute value of the correlation coefficient (CC) of 2D, SAE, and 3D features was 0.3318 ± 0.1196, 0.2149 ± 0.0361, and 0.4189 ± 0.0882, respectively. While for the association with Ki-67 index and rate of nuclear mitosis, the 3D features also showed higher correlations, with CC as 0.4053 ± 0.0786 and 0.4061 ± 0.0806. In addition, the 3D feature-based signatures showed optimal performance in clinical factor prediction. Significance. We found relationships between imaging features, clinical factors, and immunohistochemical markers. The 3D features showed higher relationships with clinical factors and immunohistochemical markers.

High-volume, label-free imaging for quantifying single-cell dynamics in induced pluripotent stem cell colonies.

To facilitate the characterization of unlabeled induced pluripotent stem cells (iPSCs) during culture and expansion, we developed an AI pipeline for nuclear segmentation and mitosis detection from phase contrast images of individual cells within iPSC colonies. The analysis uses a 2D convolutional neural network (U-Net) plus a 3D U-Net applied on time lapse images to detect and segment nuclei, mitotic events, and daughter nuclei to enable tracking of large numbers of individual cells over long times in culture. The analysis uses fluorescence data to train models for segmenting nuclei in phase contrast images. The use of classical image processing routines to segment fluorescent nuclei precludes the need for manual annotation. We optimize and evaluate the accuracy of automated annotation to assure the reliability of the training. The model is generalizable in that it performs well on different datasets with an average F1 score of 0.94, on cells at different densities, and on cells from different pluripotent cell lines. The method allows us to assess, in a non-invasive manner, rates of mitosis and cell division which serve as indicators of cell state and cell health. We assess these parameters in up to hundreds of thousands of cells in culture for more than 36 hours, at different locations in the colonies, and as a function of excitation light exposure.

Ki-67 Proliferation Index Is Associated With Tumor Grade and Survival in Pleural Epithelioid Mesotheliomas.

Pleural epithelioid mesothelioma (PEM) is divided into low and high grades based on nuclear atypia, mitoses, and necrosis in the tumor. Assessing mitoses and nuclear atypia tend to be labor-intensive with limited reproducibility. Ki-67 proliferation index was shown to be a prognostic factor in PEM, but its performance has not been directly correlated with tumor grade or mitotic score. This study evaluated the potential of Ki-67 index as a surrogate of tumor grade. We also compared the predictability of mitoses and Ki-67 index for overall survival (OS). Ninety-six PEM samples from 85 patients were identified from the surgical pathology file during 2000-2021 at our institution, and all glass slides were reviewed by 2 pulmonary pathologists to confirm the diagnosis and assign the tumor grade. Digital image analysis (DIA) was done for Ki-67 index. The agreement on tumor grading between 2 reviewers was moderate (kappa value = 0.47). The correlation between mitotic count (average count by 2 reviewers) and Ki-67 index was 0.65. The areas under the curve for predicting tumor grade by mitotic score and Ki-67 index were 0.84 and 0.74 (reviewer 1) and 0.85 and 0.81 (reviewer 2), respectively. High Ki-67 index and mitoses were significantly associated with poor OS ( P =0.03 and 0.0005, using 30% and 10/2mm 2 as cutoffs, respectively). In conclusion, Ki-67 index by DIA was associated with tumor grade as well as mitotic count, and its predictability for OS was comparable to that of mitotic score, thus being a potential surrogate for tumor grade.

Jejunal gastrointestinal stromal tumor that developed in a patient with neurofibromatosis type 1: a case report

BackgroundNeurofibromatosis type 1 (NF1) is known to be associated with the frequent occurrence of unique gastrointestinal stromal tumors (GISTs), preferably occurring in the small intestine, with no mutations in the c-kit proto-oncogene or platelet-derived growth factor receptor-alpha (PDGFRA), with a high tendency for multifocal development, indolent nature, with low proliferation activity and favorable prognosis.Case presentationA woman in her forties visited her local doctor complaining of menstrual pain; a large mass was detected in her lower abdomen, and she was referred to our hospital. The patient had hundreds of skin warts and café au lait spots. The patient’s mother had been diagnosed with type 1 neurofibromatosis. The patient met the diagnostic criteria for NF1 and was diagnosed with NF1. Ultrasonography showed a large heterogeneous cystic mass with various echo patterns, solid compartments and multiple septations. Magnetic resonance imaging showed a multilocular cystic mass with liquid content exhibiting various intensities, including that of blood. A small round solid mass was also observed close to the cystic tumor. Contrast-enhanced computed tomography showed that the round solid mass showed strong enhancement in the early phase, unlike the cystic tumor component. Open laparotomy revealed a multicystic exophytic tumor measuring 11.5 cm originating from the jejunal wall, 20 cm distal to the duodenojejunal flexure. A solid tumor measuring 2.1 cm was also found on the anal side of the large tumor. We resected the short segment of the jejunum, including the two lesions. Microscopic findings revealed that the cystic and solid tumors consisted of spindle-shaped tumor cells showing little atypia with a fascicular or bundle arrangement. Nuclear mitosis was scarce. Immunostaining of the tumor cells showed positive staining for KIT and DOG1 and negative staining for S100 and desmin. The NF1 patient was diagnosed with multiple GISTs accompanied by intratumoral hemorrhagic denaturation arising from the jejunum. The TNM staging was pT4N0M0, stage IIIA.ConclusionWe report a case of GISTs associated with NF1 that showed a jejunal origin, multifocal development and few mitotic figures. The recurrence risk, survival prognosis and need for adjuvant chemotherapy, particularly in cases where the initial GIST exhibits a very indolent pathology in NF1-related GISTs, remain to be elucidated.

Long-term outcomes and predictors of recurrence in node-negative early stage breast cancer patients.

We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study. Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient's demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test. A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence. Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

Endometrium Kanseri Alt Tiplerinde Mikrosatellit İnstabilite (MSI) ve p16/p53 Gen Durumu: Tümör Saldırganlığı ile İlişkisi

Aim: Microsatellite instability (MSI) has recently emerged as one of the most important pathways in endometrial carcinogenesis, especially in endometrioid subtype (type I). However, non-endometrioid subtypes, like serous, papillary or mucinous tumors, have long been known to overexpress p16 and/or p53 genes. In the present study, we investigated the immunohistochemical (IHC) panel in all subtypes of endometrial cancer (EC), and correlated the results with nuclear mitosis index (Ki-67) as a marker of tumoral mitosis rate. Methods: Medical records of patients admitted with EC and underwent surgery between 2010 and 2022 were reviewed. IHC panel results of estrogen and progesterone receptors (ER, PR), mismatch repair (MMR) proteins MLH1, PMS2, MSH2, MSH6, Ki-67 and p16/p53 status were recorded. Chi square test was used for statistical analysis. Results: Total of 44 female patients (with pathology reports including all of IHC panel markers) were included. Mean age was 64.1±12.51 years. Type I EC was the most common pathology (72%). ER and PR positivity were very prominent in type I tumors in comparison with non-endometrioid (type II) tumors (84% vs 16%, respectively; p

Abstract P2-11-16: Computerized Measurements of Nuclear Morphology Features, Mitosis Rate, and Tubule Formation from H&E Images Predicts Disease-Free Survival in Patients with HR+ & LN+ Invasive Breast Cancer from SWOG S8814

Abstract Background: Lymph node (LN) involvement is a strong indicator of poor prognosis for breast cancer (BC), with adjuvant chemotherapy remaining fundamental to management of these patients. SWOG S8814 was a Phase III randomized trial of postmenopausal patients with pathologic LN-positive BC who were hormone receptor positive (HR+). The objectives of the clinical trial were to compare disease free survival (DFS) and overall survival (OS) of 1) these postoperative patients treated with a combination of cyclophosphamide, doxorubicin, fluorouracil (CAF) plus tamoxifen versus tamoxifen alone; and 2) patients treated with CAF followed by tamoxifen versus CAF plus concurrent tamoxifen. In this study we sought to evaluate the potential of applying computational image analysis on whole slide images (WSI) for predicting DFS and OS in SWOG S8814. Methods: A cohort of 135 patients (N=53 DFS event) diagnosed with HR+ & LN+ BC from clinical trial ECOG 2197 was utilized as training set D1. Validation set D2 comprised 630 patients (N=260 DFS event, N=195 death) with HR+& LN+ BC from SWOG S8814. Three deep learning models were employed to respectively detect nuclei, mitosis, and tubules in WSIs. Subsequently, a total of 1,810 features relating to nuclear morphology (e.g., spatial distribution, shape, texture, orientation), mitotic activity (e.g., mitosis hotspot, mitotic rates) and tubule formation (e.g., tubular nuclei distribution, ratio of tubule to non-tubule area) were extracted from each WSI. A lasso regularized Cox regression model (IbRiS) was trained on D1 to respectively identify four features from each of the feature categories (nuclei morphology, mitotic activity, and tubule formation) most strongly associated with DFS, a continuous risk score based on the selected features was then constructed. An optimal risk threshold was identified on D1 to dichotomize the risk scores into high vs. low risk of recurrence categories. Blinded validation of the machine learning model on SWOG S8814 using Cox regression was performed by SWOG to evaluate its performance in terms of DFS and OS. Results: In D2, patients identified as high risk of recurrence by IbRiS had a significantly worse prognosis in terms of DFS with hazard ratio=1.30 (p=0.039, 95% CI=1.01-1.66). IbRiS was also found to be significantly prognostic of OS with hazard ratio=1.38 (p=0.026, 95% CI=1.04-1.83). IbRiS was however, neither prognostic of DFS (HR = 1.20; 95% CI 0.93-1.54) nor OS (HR = 1.28; 95% CI 0.96-1.71) in multivariable analysis adjusting for treatment, tumor size, and number of positive nodes. IbRiS was also not a significant predictor of chemotherapy benefit (DFS p=0.45; OS p=0.25). Conclusion: We developed a prognostic model (IbRiS) based on the combined features of nuclear morphology, mitosis count, and tubule formation that can help further risk stratify HR+ & LN+ BC patients by only using H&E slides. Citation Format: Yuli Chen, William E. Barlow, Haojia Li, Cheng Lu, Andrew Janowczyk, German Corredor, Shridar Ganesan, Michael Feldman, Pingfu Fu, Hannah Gilmore, Kathy S. Albain, Lajos Pusztai, James Rae, Daniel Hayes, Andrew K. Godwin, Alastair M. Thompson, Anant Madabhushi. Computerized Measurements of Nuclear Morphology Features, Mitosis Rate, and Tubule Formation from H&E Images Predicts Disease-Free Survival in Patients with HR+ & LN+ Invasive Breast Cancer from SWOG S8814 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-16.

Sinonasal myxoma/fibromyxoma: case report and literature review

Sinonasal myxoma/fibromyxoma is a rare benign neoplasm of uncertain histogenesis which can be locally aggressive. Surgical resection is the preferred management. We present a rare case of sinonasal fibromyxoma in a 30-year-old male who presented with a frontal sinus tumour. Histopathological examination showed a hypocellular spindle to stellate cell neoplasm with a myxoid to collagenous background, without nuclear atypia, mitoses or necrosis. The tumour expressed vimentin, SMA, h-caldesmon and b-catenin (focal).

Ahctf1 and kras mutations combine to amplify oncogenic stress and restrict liver overgrowth in a zebrafish model of hepatocellular carcinoma.

The nucleoporin (NUP) ELYS, encoded by AHCTF1, is a large multifunctional protein with essential roles in nuclear pore assembly and mitosis. Using both larval and adult zebrafish models of hepatocellular carcinoma (HCC), in which the expression of an inducible mutant kras transgene (krasG12V) drives hepatocyte-specific hyperplasia and liver enlargement, we show that reducing ahctf1 gene dosage by 50% markedly decreases liver volume, while non-hyperplastic tissues are unaffected. We demonstrate that in the context of cancer, ahctf1 heterozygosity impairs nuclear pore formation, mitotic spindle assembly, and chromosome segregation, leading to DNA damage and activation of a Tp53-dependent transcriptional programme that induces cell death and cell cycle arrest. Heterozygous expression of both ahctf1 and ranbp2 (encoding a second nucleoporin), or treatment of heterozygous ahctf1 larvae with the nucleocytoplasmic transport inhibitor, Selinexor, completely blocks krasG12V-driven hepatocyte hyperplasia. Gene expression analysis of patient samples in the liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas shows that high expression of one or more of the transcripts encoding the 10 components of the NUP107-160 subcomplex, which includes AHCTF1, is positively correlated with worse overall survival. These results provide a strong and feasible rationale for the development of novel cancer therapeutics that target ELYS function and suggest potential avenues for effective combinatorial treatments.

Geometric tumor embolic budding characterizes inflammatory breast cancer.

Inflammatory breast cancer (IBC) is characterized by numerous tumor emboli especially within dermal lymphatics. The explanation remains a mystery. This study combines experimental studies with two different IBC xenografts with image algorithmic studies utilizing human tissue microarrays (TMAs) of IBC vs non-IBC cases to support a novel hypothesis to explain IBC's sina qua non signature of florid lymphovascular emboli. In the human TMAs, compared to tumor features like nuclear grade (size), mitosis and Ki-67 immunoreactivity which show that IBC is only modestly more proliferative with larger nuclei than non-IBC, what really sets IBC apart is the markedly greater number of tumor emboli and distinctly smaller emboli whose numbers indicate geometric or exponential differences between IBC and non-IBC. In the experimental xenograft studies, Mary-X gives rise to tight spheroids in vitro which exhibit dynamic budding into smaller daughter spheroids whereas Karen-X exhibits only loose non-budding aggregates. Furthermore Mary-X emboli also bud dramatically into smaller daughter emboli in vivo. The mechanism that regulates this involves the generation of E-cad/NTF1, a calpain-mediated cleavage 100kDa product of 120kDa full length membrane E-cadherin. Inhibiting this calpain-mediated cleavage of E-cadherin by blocking either the calpain site of cleavage (SC) or the site of binding (SB) with specific decapeptides that both penetrate the cell membrane and mimic either the cleavage site or the binding site on E-cadherin, inhibits the generation of E-cad/NTF1 in a dose-dependent manner, reduces spheroid compactness and decreases budding. Since E-cad/NFT1 retains the p120ctn binding site but loses the α-and β-catenin sites, promoting its 360° distribution around the cell's membrane, the vacilating levels of this molecule trigger budding of both the spheroids as well as the emboli. Recurrent and geometric budding of parental emboli into daughter emboli then would account for the plethora of emboli seen in IBC.

A Rare Case of Paratesticular Cystadenoma with Ovarian Stroma Found by Scrotal Ultrasound on a Cirrhotic Patient with Elevated Alpha-fetoprotein

Abstract Introduction/Objective Paratesticular cystadenoma with ovarian stroma is a rare benign cyst-forming neoplasm with less than 10 cases reported in the literature. Typically, it presents in men aged 11 to 68 years (average 30) and is asymptomatic. The tumor is hypothesized to represent the efferent ductulus undergoing metaplastic change, the vestigial remnants of Mullerian duct, or mesothelium of the tunica vaginalis. Most tumors are considered benign, but a few cases of malignant transformation have been reported. Methods/Case Report We present a case of a 54-year-old male with a history of cirrhosis and elevated alpha-fetoprotein (17.85 ng/ML) who was found to have a paratesticular mass by scrotal ultrasound. Clinical history was obtained from review of electronic medical record. CD10 (Novocastra Clone 56C6) and progesterone receptor (PR) (Leica Clone 16) Immunoperoxidase stains were performed following the vendor recommendations. Surgical excision revealed a 0.6-cm polypoid nodule on tunica albuginea that was entirely submitted. Microscopically, the tumor was comprised of cystic spaces lined by cuboidal epithelium identical to that of the Fallopian tubes. There was a sparse spindle-shaped stroma underlying the epithelium similar to ovarian stroma. No nuclear atypia or mitosis was found. Immunoperoxidase stains showed the epithelium was positive for PR, and the stroma was positive for CD10. No evidence of germ cell tumor was identified. Results (if a Case Study enter NA) NA. Conclusion Characteristic histologic and immunophenotypic findings can aid in the diagnosis of paratesticular cystadenoma with ovarian stroma. Surgical resection for histological confirmation and long-term monitoring for the potential recurrence and metastatic spread are required.

S2406 A Case of Cervical Esophageal Adenocarcinoma Arising From Gastric Inlet Patch: A Benign Lesion With Malignant Potential

Introduction: Esophageal adenocarcinoma is typically localized to the distal third of the esophagus. It is associated with long-standing acid reflux and resultant Barrett’s esophagus. In contrast, adenocarcinoma in the proximal esophagus without Barrett’s metaplasia is extremely rare. A gastric inlet patch (GIP) is a lesion of ectopic gastric mucosa usually found in the cervical esophagus and is considered a benign lesion. However, albeit rare, malignant transformation of GIP can occur. Here, we present a case of cervical esophageal adenocarcinoma arising from gastric inlet patch. Case Description/Methods: A 50-year-old male with GERD presented with a 6-month history of progressive dysphagia to solids and liquids and 20-pound weight loss. He reported a 1 pack-year smoking history but quit 30 years prior and consumed alcohol socially. Family history was negative for esophageal cancer. Upper endoscopy (HQ190F) showed a malignant stricture (2 cm long, 6mm diameter) at 18 cm from the incisors and a gastric inlet patch adjacent to the stricture. The endoscope was downsized (XP190N), and the stricture was dilated (24F) and traversed. The Z-line was at 40 cm with Barrett’s esophagus extending from 36 cm to 40 cm. Pathology of biopsies from the stricture showed acute and chronic inflammation with increased intraepithelial eosinophils suggestive of acid reflux. CT scan of the neck with contrast showed a heterogeneously enhancing ill-defined mass involving the cervical esophagus below the cricoid cartilage indenting the posterior margin of the trachea. Bronchoscopy was negative for bronchogenic cancer. Endoscopic ultrasound showed a non-circumferential hypoechoic mass in the cervical esophagus 18 cm from the incisors extending to 20 cm. The mass was predominantly extrinsic but was also noted to have a luminal component and poorly defined endosonographic borders. Pathology of FNAB showed moderately differentiated adenocarcinoma (Figure). Discussion: Proximal esophageal adenocarcinoma is extremely rare, making up less than 1% of esophageal cancers. Case studies have been published associating GIP and esophageal adenocarcinoma, but the pathogenesis of malignant transformation remains unclear. There are no established screening guidelines for ectopic gastric mucosa and routine biopsies are not recommended as dysplasia within GIP is rare. GIP may be overlooked during EGD and NBI exam may improve detection rates. Our case re-emphasizes careful examination of GIP and to strongly consider biopsy if abnormal.Figure 1.: A) Endoscopic view of malignant stricture 18 cm from incisors. Gastric inlet patch (arrow) adjacent to stricture. B) Endoscopic ultrasound image at the level of esophageal stricture showing irregular hypodensity suggestive of malignancy. C) Pathology of biopsy performed through fine needle aspiration (EUS) of upper esophageal mass demonstrating moderately differentiated adenocarcinoma, cribriform pattern, with mild nuclear pleomorphism, abundant mitoses, and apoptosis (H&E, 10x).

Nuclear envelope protein lamin B receptor protects the genome from chromosomal instability and tumorigenesis.

Lamin B Receptor (LBR) is an inner nuclear membrane protein that assembles the nuclear envelope post mitosis. Here we show that LBR depletion induces mitotic defects accompanied by recurrent chromosomal losses. In addition, LBR knockdown results in nuclear aberrations such as nuclear blebs and micronuclei, with chromosomes showing higher frequency of losses, being enriched within the micronucleus. Furthermore, doxycycline-induced conditional depletion of LBR significantly increased tumor volumes that form within the subcutaneous xenografts of mice. Of note, the tumor-derived primary cells recapitulated chromosomal losses and gains, revealing a novel role for LBR as a tumor suppressor. Co-immunoprecipitation of LBR uncovered an association of LBR with telomere-associated factors. Interestingly, qPCR array-based gene expression profiling showed a significant upregulation of telomere repeat-binding factor 1 (TRF1) upon LBR depletion. Remarkably, TRF1 knockdown in the background of LBR depletion maintains chromosomal stability, unraveling a novel mechanism involving LBR and TRF in the maintenance of chromosomal stability in colorectal cancer cells.

Dermoscopy of trichoblastic carcinoma

Trichoblastic carcinoma is a rare malignant adnexal tumor deriving from the hair follicle. It is clinically highly similar to basal cell carcinoma (BCC), with a greater malignant potential and a higher metastatic risk [1,2]. Histopathology reveals lobules of small, basaloid cells, cytonuclear pleiomorphism, and numerous mitoses with follicular differentiation [1]. It is important to differentiate these two entities as they follow different clinical courses and, therefore, require different treatments [2]. To our knowledge, dermoscopy of this tumor has only been described once, showing scattered specks of brown pigment in a trichoblastic carcinoma of the scalp [3]. Herein, we present a dermoscopic description of a recurrent trichoblastic carcinoma. A 93-year-old patient, who underwent an excision of a lesion of the left nasolabial fold two years previously with no record of histopathology, presented to our dermatology department with a lesion on the same site of excision evolving for the lasts six months. A clinical examination revealed a well-limited ulceration surrounded by a bluish, peripheric halo with an infiltrated base. Pigmented papules and telangiectasias were also observed along the scar of the nasolabial fold (Fig. 1). Dermoscopy showed blue, ovoid nests, brown and blue globules, telangiectasias, and a central ulceration (Fig. 2). A biopsy revealed a dermal tumor proliferation made from lobules and trabeculae of basaloid cells with nuclear atypia and numerous mitoses, which was more in favor of a trichoblastic carcinoma than a BCC. A radiological assessment revealed no regional or distant metastasis. The patient was referred to the plastic surgery department for further management.

NUP153 promotes HCC cells proliferation via c-Myc-mediated downregulation of P15INK4b

Background and aimNucleoporin NUP153 (NUP153) is involved in the regulation of nuclear transportation, mitosis, and tumor progression in various cancer cells. we aimed to investigate the roles of NUP153 in hepatocellular carcinoma (HCC). MethodsNUP153 expression level and its relationship with clinical prognosis were analyzed based on The Cancer Genome Atlas (TCGA). Quantitative real-time PCR (qRT-PCR), Western Blot (WB), and Immunohistochemistry (IHC) were used to assess NUP153 expression in tissues and cell lines. Loss-of-function experiments were implemented for exploring the roles of NUP153 in HCC cells. Ultimately, how NUP153 exerted biological functions was plumbed by performing rescue assays in HCC. ResultsNUP153 expressed highly in HCC tissues and cell lines. Silencing NUP153 inhibited cellular multiplication, G1/S transition, migration, and triggered cytoskeletal rearrangement of Huh7 and HepG2 cells. Knockdown NUP153 caused up-regulation of mRNA and protein levels of P15, and siRNA deprivation of P15 partially reversed the function of low-level NUP153 in HCC. Meanwhile, silencing NUP153 caused down-regulation of mRNA and protein levels of c-Myc. Furthermore, the up-regulation of P15 and cell G1/S phase arrest induced by silencing NUP153 were partially reversed by overexpression of c-Myc. ConclusionsNUP153 increases the proliferation ability of cells via the c-Myc/P15 axis in HCC.

Fine needle aspiration cytology of metastatic carcinomas with papillary architecture: A systemic assessment of clinical, cytological and immunohistochemical parameters.

Papillary structures are frequently encountered in metastatic carcinomas from various organs and tumours of different histotypes. This study aims to investigate the predictive value of fine needle aspiration cytology (FNAC), immunohistochemistry (IHC) and the clinical parameters which can be examined in the assessment of the primary sites of metastatic carcinomas with papillary architecture. FNAC samples of metastatic carcinomas with papillary architecture were evaluated for overall cellularity, epithelial cohesion, background features, papillary architecture, cytology and IHC. The corresponding clinical information was also reviewed. A total of 130 cases were included. The most common primary sites were thyroid (38.5%), lung (30.8%) and gynecological organs (22.3%); the others were pancreaticobiliary, urothelial, colorectal, and esophageal. Age (P=0.039), biopsy site (P<0.001) and laterality (P=0.006) correlated with primary site. Papillary structures were confirmed on biopsy/excision of most cases (n=85/87, 97.7%). Thyroid primaries exhibited broad papillary stalks, thin lining epithelium, fewer epithelial polymorphs, and the presence of background giant cells and histiocytes (P=0.021- < 0.001). Low-grade cytological features, nuclear grooves and inclusions (P<0.001) were seen in thyroid primaries. High-grade features (P<0.001-0.49), multinucleated tumour cells, apoptotic bodies and mitoses (P<0.001-0.49) were more common in lung/gynecological primaries. Multivariate analysis identified nuclear/cytoplasmic ratio, chromatin character, the presence of nuclear grooves and mitosis as independent features (P=0.001-0.024). TTF1/TGB/PAX8 panel results showed good agreement with the cytological assessment and site of primary. Papillary structures and cytological features are reproducible in FNAC assessment of metastases and their corresponding primary sites. Cytological features, IHC and clinical information are invaluable in determining the primary site.

Screening of Differentially Expressed Genes and Localization Analysis of Female Gametophyte at the Free Nuclear Mitosis Stage in Pinus tabuliformis Carr.

Female sterility is a common phenomenon in the plant world, and systematic research has not been carried out in gymnosperms. In this study, the ovules of No. 28 sterile line and No. 15 fertile line Pinus tabuliformis were used as materials, and a total of 18 cDNA libraries were sequenced by the HiSeqTM 4000 platform to analyze the differentially expressed genes (DEGs) and simple sequence repeats (SSRs) between the two lines. In addition, this study further analyzed the DEGs involved in the signal transduction of plant hormones, revealing that the signal pathways related to auxin, cytokinin, and gibberellin were blocked in the sterile ovule. Additionally, real-time fluorescent quantitative PCR verified that the expression trend of DEGs related to plant hormones was consistent with the results of high-throughput sequencing. Frozen sections and fluorescence in situ hybridization (FISH) were used to study the temporal and spatial expression patterns of PtRab in the ovules of P. tabuliformis. It was found that PtRab was significantly expressed in female gametophytes and rarely expressed in the surrounding diploid tissues. This study further explained the molecular regulation mechanism of female sterility in P. tabuliformis, preliminarily mining the key factors of ovule abortion in gymnosperms at the transcriptional level.

An Immunohistochemical Study of Epidermal Growth Factor Receptor in Sebaceous Carcinoma of the Eyelid: A Potential Therapeutic Target.

To investigate the relationship between epidermal growth factor receptor (EGFR) expression and clinicopathological characteristics in sebaceous carcinoma (SbC) of the eyelid. Clinical records and microscopic slides of 102 cases of SbC in the eyelid were reviewed. An immunohistochemical antibody for EGFR was employed. Differentiation, pagetoid spread, and mitosis were evaluated. Of the 102 patients, 46 (45.1%) cases were male and 56 (54.9%) cases were female (male:female, 1:1.2). The mean age of the patients was 57.32 ± 13.23 years (range, 26-85 years). Fifty-two (51%) cases occurred in the right eye and 50 (49%) cases in the left eye. The stage T1 and stage T2 cases were 71 (69.6%) and 31 (30.4%), respectively. There were 69 (67.6%) cases with pagetoid spread and 33 (32.4%) cases without pagetoid spread. There were 15 (14.7%) well-differentiated cases, 33 (32.4%) moderately differentiated cases, and 54 (52.9%) poorly differentiated cases. There was 1 (1%) case of 0 to 1/ high power field (HPF) mitosis, 46 (45.1%) cases of 2 to 5/HPF mitoses, and 55 (53.9%) cases of >5/HPF mitoses, respectively. The EGFR positivity of SbCs was 97.1% (99 cases) with 2% (2 cases) weak expression, 46.1% (47 cases) moderate expression, and 49% (50 cases) strong expression. While EGFR was weakly positive only in a few conjunctival epithelial cells and basal cells of the sebaceous glands. The EGFR expression of SbCs was related to the clinic T category statistically ( P = 0.048) but not related to age, gender, differentiation, nuclear mitosis, and pagetoid spread of these tumors statistically ( P > 0.05). And the differentiation of these SbCs was related to the mitosis of these tumors statistically ( P < 0.001). The EGFR expression of SbCs was related to the tumor stage statistically, which implied that EGFR might be used as a prognostic marker of SbCs. EGFR is expressed in most SbC cases, which implied that it might act in the tumorigenesis mechanisms of SbC and could be a therapeutic target in the treatment of SbC for some metastatic cases.

Malignant giant solitary fibrous tumour of the mediastinum; masquerading Triton tumour

BackgroundMalignant Solitary fibrous tumour (SFT) is an uncommon mesenchymal tumour with aggressive clinical behaviour as compared to its benign counterpart. There are only a handful of reports of extra-pleural malignant SFT arising from the mediastinum.Case presentationA 68-year-old male, presented with a history of cough and breathlessness for 2 weeks. Computed tomography (CT) scan revealed a large 11.6 × 11.3x18cm anterior mediastinal mass with extension to right hemithorax. The patient underwent excision of the mass after a biopsy confirmation of mesenchymal tumour. Histological examination of resection specimen revealed a spindle cell tumour with hypo and hypercellular areas, arranged in fascicular, focal storiform and hemangio-pericytomatous vasculature pattern. Moderate to marked nuclear atypia, frequent mitosis and areas of necrosis were noted. On immunohistochemistry (IHC), the tumour cells were positive for CD34, Bcl2, MIC2 (dot-like) and focally for S100 and Desmin. Although, the possibility of a malignant peripheral nerve sheath tumour with heterologous rhadomyosarcomatous differentiation (Triton tumour) was considered, however IHC for STAT6 confirmed it to be a malignant SFT. The patient developed recurrence within 1 year after surgery and despite multi-modality treatment (Re-excision, Chemotherapy and Radiotherapy) succumbed within 14 months from point of presentation.ConclusionMalignant SFT is a rare aggressive tumour that should be considered as a differential diagnosis in the mediastinum and a broad panel of IHC markers including STAT6 may be required to confirm the diagnosis.