URI alleviates tyrosine kinase inhibitors-induced ferroptosis by reprogramming lipid metabolism in p53 wild-type liver cancers.

The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

Phosphotriesterase-related protein as a novel prognostic predictor for hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth incidence of cancer and the third leading cause of cancer mortality in the world. Facing the ever-increasing population of HCC patients, there is still an urgent need to find good diagnostic and prognostic markers to explore new therapeutic targets. Phosphotriesterase-related (PTER) protein, an expressed protein in the liver and injured or ploycystic kidneys, was reported to be correlated with serum aspartate aminotransferase (AST) and alanine transaminase (ALT). Our study aimed to investigate the expression of PTER protein in HCC patients and the association between PTER protein expression with clinicopathological features of HCC. METHODS: Western blot analysis and immunohistochemistry (IHC) were performed in paired para-tumor and liver tumor tissues and HCC tissue microarray (TMA) to detect PTER protein expression. Correlation between PTER protein and prognostic factors were analyzed through univariate and multivariate analysis. RESULTS: We identified that PTER protein was significantly up-regulated in HCC tumors. Our data revealed that high PTER protein expression was associated with aggressive clinicopathological features of HCC, such as advanced tumor staging, vascular invasion, recurrence, and shorter overall survival (OS) and disease-free survival (DFS) time. Besides, in multivariate analyses, PTER protein was an independent predictor for OS (P=0.004) and DFS (P=0.013) for HCC patients. Meanwhile, the prognosis of patients with high PTER protein is much worse than those with low PTER protein expression. CONCLUSIONS: PTER protein expression is raised in HCC tissues and may be a potential prognostic predictor for HCC patients.

Cytomorphology and immunocytochemical features of ovarian granulosa cell tumors in ascites or peritoneal washings: A retrospective review.

AIM: To summarize the cytomorphology and immunocytochemistry features of OGCT in ascites or peritoneal washings. METHODS: All cases of histology sections, cytology smears, cell block slides and immunohistochemical staining were reviewed. A panel of immunohistochemistry antibodies consisting of Inhibin, Calretinin, BerEP4 and MC was performed for diagnosis and differential diagnosis. RESULTS: Seven positive cases (21.2%) in ascites and peritoneal washings were identified in 33 patients with OGCT, which is higher than early studies with positive rate of 7.4%. Clinicopathologic features including tumor size and the incidence of endometrial atypical hyperplasia or carcinoma (EAH/EC) displayed no statistical difference between groups with positive and negative cytology. Immunocytochemical results usually showed typical staining pattern with α-inhibin, calretinin positive and BerEP4, MC negative. Features of granulosa cells, including nuclear hyperplasia and overlapping, can be observed in all seven positive cases. Nuclear grooves or small conspicuous nucleoli were occasionally observed in the smear. However, features of cell clusters mimicking Call-Exner bodies, cytoplasmic vacuoles or single cell necrosis were not found on smear. Call-Exner bodies and mitosis can only be found on cell blocks. All cases of follow-up information were available and three cases displayed progression and there was a statistical difference between groups with positive and negative cytology. CONCLUSION: OGCT with positive cytology in ascites and peritoneal washings tend to have a larger tumor size and higher rates of disease progression. A panel of complementary biomarkers can greatly increase the detection rate and help in differential diagnosis in ascites or peritoneal washings of OGCT.

Impact of antithrombotic drugs on the accuracy of fecal occult blood testing for advanced colorectal neoplasia screening: a meta-analysis and systematic review.

BACKGROUND: The current meta-analysis was conducted to determine whether antithrombotic drug use would affect the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia. METHODS: Articles published between 2000 and 2019 were systematically retrieved and screened according to the inclusion and exclusion criteria by two reviewers independently. Pooled analyses were conducted with a fixed-effect model if no apparent heterogeneity (I2 ≥ 50%) was found between studies; otherwise, the random effects model would be used. Sensitivity analysis and subgroup analysis were also conducted using Review Manager 5.3. RESULTS: Pooled analysis revealed that aspirin and nonsteroidal anti-inflammatory drugs were associated with a decrease in the positive predictive value of fecal occult blood testing for advanced colorectal neoplasia screening, with a RR of 0.89 (95% CI: 0.84-0.94) and 0.88 (95% CI: 0.84-0.93, p<0.001) respectively. Subgroup analysis based on data limited to high-quality studies, fecal immunochemical testing, or in Caucasians also showed that the use of aspirin/NSAID drugs decreased the accuracy for advanced colorectal neoplasia screening. CONCLUSION: Aspirin/NSAIDs and direct oral anticoagulants rather than warfarin may decrease the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia screening.

Using Silva pattern system to predict prognosis and plan treatment of invasive endocervical adenocarcinoma: a single-center retrospective analysis.

BACKGROUND: This study evaluated the prognostic value of the Silva pattern system for invasive endocervical adenocarcinoma (EAC) by analysing its association with clinical and pathological features to provide more appropriate clinical management. METHODS: A retrospective analysis including 63 patients with pathological diagnosis of invasive EAC was performed from March 2011 to December 2016 at our hospital. All pathological slides were reviewed by three senior pathologists, and cases were stratified into patterns A, B, or C by consensus according to the Silva pattern system criteria. Clinicopathological characteristics and follow-up of the three Silva subgroups were analysed. RESULTS: Silva A, B, and C EAC patients were compared based on tumour size, clinical stage, lymphovascular invasion (LVI), and depth of invasion (DOI). The differences were found to be statistically significant (p < 0.01). There was no statistically significant difference in the proportion of lymph node metastasis among the three groups (p > 0.05) or in the recurrence and mortality rates of patients with Silva A, B, and C EAC (p > 0.05). Single factor analysis showed that tumour size, clinical stage, lymph node metastasis, LVI, and DOI were related to postoperative recurrence, whereas age, Silva classification, and postoperative recurrence were not correlated. CONCLUSION: The Silva classification system can predict lymph node status and prognosis of invasive EAC, but it cannot be used as an independent indicator. Individualized treatment plans should be adopted for patients with EAC.

ELOVLs Predict Distinct Prognosis Value and Immunotherapy Efficacy In Patients With Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with high prevalence worldwide and poor prognosis. It has been verified that elongation of very-long-chain fatty acids gene family (ELOVLs), a group of genes that responsible for elongation of saturated and polyunsaturated fatty acids, participate in the pathogenesis and development of multiplex disease including cancers. However, the functions and prognosis of ELOVLs in HCC are still indistinguishable. Methods: First, we searched the mRNA expression and survival data of ELOVLs in patients with HCC via the data of The Cancer Genome Atlas (TCGA). The prognosis value of ELOVLs on HCC was assessed by Kaplan-Meier plotter and Cox regression analysis. reverse transcription quantitative- polymerase chain reaction (RT-qPCR), Western blot (WB), and immunohistochemistry were applied to assess the specific mRNA and protein expression of ELOVLs in HCC clinical specimens of our cohort. Then, the functional enrichment of ELOVL1 especially the pathways relating to the immune was conducted utilizing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analysis. Additionally, TIMER, CIBERSOR, and tumor immune dysfunction and exclusion (TIDE) were employed to evaluate the relationship between ELOVL1 and immune responses. Last, the correlation of ELOVL1 with genome heterogeneity [microsatellite instability (MSI), tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), homologous recombination deficiency (HRD), purity, ploidy, loss of heterozygosity (LOH), and neoantigens] and mutational landscape were also evaluated basing on the date in TCGA. Results: Significant expression alteration was observed in ELOVLs family at the pan-cancer level. In liver cancer, ELOVL1 and ELOVL3 were strongly associated with poor prognosis of HCC by survival analysis and differential expression analysis. Immunohistochemistry microarray, WB, and RT-qPCR confirmed that ELOVL1 but not ELOVL3 played an important role in HCC. Mechanistically, functional network analysis revealed that ELOVL1 might be involved in the immune response. ELOVL1 could affect immune cell infiltration and immune checkpoint markers such as PD-1 and CTLA4 in HCC. Meanwhile, high expression of ELOVL1 would be insensitive to immunotherapy. Correlation analysis of immunotherapy markers showed that ELOVL1 has been associated with MSI, TMB, and oncogene mutations such as TP53. Conclusion: ELOVLs play distinct prognostic value in HCC. ELOVL1 could predict the poor prognosis and might be a potential indicator of immunotherapy efficacy in HCC patients.

Screening of Hepatocellular Carcinoma Patients with High Risk of Early Recurrence After Radical Hepatectomy Using a Nomogram Model Based on the γ-Glutamyl Transpeptidase-to-Albumin Ratio.

BACKGROUND AND PURPOSE: The present study aimed to establish a γ-glutamyl transpeptidase-to-albumin ratio (GAR)-based nomogram model to predict early recurrence of hepatocellular carcinoma (HCC) after radical surgery. METHODS: Patients enrolled in this study were randomly allocated into a train and validation cohort in a ratio of 7:3. The Least Absolute Shrinkage and Selection Operator (LASSO) proportional hazards model and cox regression model were combined to identify independent risk factors related to HCC recurrence. Based on these risk factors, a predictive nomogram was constructed and validated in both inner and outer test cohorts. The performance of the nomogram was evaluated by C-index, the area under the receiver operating characteristic curve (AUC), the calibration curve and decision curve analysis. RESULTS: The tumor size, tumor number, BCLC stage, microvascular invasion (MVI) and GAR value were identified as independent risk factors related to HCC recurrence and used to construct the predictive nomogram. AUC of the nomogram showed satisfactory accuracy in predicting 1-, 3- and 5-year disease-free survival. The calibration curve showed agreement between the ideal and predicted values. The risk score more than 72 as calculated by the nomogram was related to early recurrence of HCC after radical surgery. DCA plots showed better clinical usability of the nomogram as compared with the BCLC staging system in all three included cohorts. CONCLUSION: The nomogram based on the GAR value may provide a new option for screening of the target HCC cohort of patients who need anti-recurrence therapy after surgery.

Dual-emission fluorescent nanoprobe based on Ag nanoclusters for sensitive detection of Cu(II).

Noble metal nanoclusters have attracted much attention because of their excellent fluorescence properties. In this work, we demonstrated a dual-emission fluorescent nanocomposite based on silver nanoclusters. First, we synthesized positively charged His-AgNCs, which emits intense blue light, and then Ag nanoclusters with stable red emission were synthesized using DHLA as the ligand. Thus a dual-emission fluorescent nanoprobe was successfully obtained through electrostatic self-assembly, with the advantages of good water solubility and excellent stability. Based on the intensity ratio of the two emission peaks, the nanoprobe can be used for selective and sensitive detection of copper ions, and presents a good linear relationship within a certain concentration range. In addition, we also designed a polymer film, and our dual-emission nanoprobe was successfully loaded onto it, which means that the visual detection of copper ions is possible. This indicates that our dual-emission fluorescent nanoprobe has potential application prospects in environmental analysis, medical diagnosis, biological detection, etc.

Integrated Bioinformatics Analysis and Validation of the Prognostic Value of RBM10 Expression in Hepatocellular Carcinoma.

Background: RBM10's function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study. Methods: Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein-protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test. Results: The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1. Conclusion: RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.

RPRD1A stabilizes NRF2 and aggravates HCC progression through competing with p62 for TRIM21 binding.

NRF2 is the master transcriptional activator of cytoprotective genes and Kelch-like ECH-associated protein 1 (Keap1), a biosensor for electrophiles and oxidation, promotes NRF2 degradation in unstressed conditions. SQSTM1/p62, an oncogenic protein aberrantly accumulated in hepatocellular carcinoma (HCC), binds and sequestrates Keap1, leading to the prevention of NRF2 degradation. Here, we show that p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A) is highly expressed in HCC tumors and correlated with aggressive clinicopathological features. RPRD1A competitively interacts with TRIM21, an E3 ubiquitin ligase of p62, resulting in the decrease of p62 ubiquitination and the increased sequestration for Keap1. Therefore, RPRD1A enhances the nuclear translocation of NRF2, which induces gene expression for counteracting oxidative stress, maintaining cancer cells survival, and promoting HCC development. Moreover, disturbing the redox homeostasis of cancer cells by genetic knockdown of RPRD1A sensitizes cancer cells to platinum-induced cell death. Our study reveals RPRD1A is involved in the oxidative stress defense program and highlights the therapeutic benefits of targeting pathways that support antioxidation.

Interactions between Pea Protein Isolate and Carboxymethylcellulose in Neutral and Acid Aqueous Systems.

Pea protein isolate (PPI), as an emerging plant protein, has gradually aroused the attention of the public, but the PPI, especially high-concentration PPI's low stability in the acidic aqueous system, was still a problem that limited its application. In this research, we investigated the interactions between relatively high concentrations of PPI (3.0%) and carboxymethylcellulose (CMC, 0-0.5%) in neutral and acid aqueous systems to explore the change of the phase behavior and stability of PPI as affected by CMC. It showed that the stability of PPI in the aqueous systems strongly depended on the CMC concentration, especially at the acidic aqueous systems. At neutral aqueous system, a certain amount addition of CMC into the PPI caused serious phase separation. While stable PPI solutions can be obtained at a narrow region around pH 4.5 to 5.5 by adding different amounts of CMC. The enhancement in the electrostatic repulsion and steric hindrance between the newly formed PPI-CMC biopolymers, as well as the increase in bulk viscosity with the adding of CMC at pH 4.5, contributed to the higher stability of PPI in acidic aqueous systems.

One-pot synthesis of folic acid modified carbonized polymer dots with red emittision for selective imaging of cancer cells.

Carbonized polymer dots (CPDs), as a novel fluorescent material, have broad application prospects in the fields of bio-imaging, bio-sensors, disease diagnosis and photovoltaic devices due to their low cost, low toxicity, easy modification and little environmental impact. In this paper, folic acid (FA) modified CPDs (FA-CPDs) are synthesized from p-Phenylenediamine (p-PD) and FA molecules using a traditional one pot hydrothermal reaction in order to detect cancer cells containing a folate receptor (FR). The synthesized FA-CPDs were characterized by transmission electron microscopy, Fourier transfrom infrared spectroscopy, x-ray photoelectron spectroscopy, x-ray diffraction, UV-vis and fluorescence techniques. The red fluorescence emission is realized by doping phosphorus atoms into the carbonized polymer. Upon excitation at 513 nm, the maximum emission wavelength of FA-CPDs aqueous solution was obtained at 613 nm. Moreover, the as-prepared FA-CPDs exhibit excellent excitation-independent behavior and good stability with high quantum yield (QY) at about 30.6%. The binding of FA-CPDs with FRs on cancer cells produces target recognition and enters the cells through endocytosis. Additionally, it is worth noting that FA-CPDs have good biocompatibility and imaging in HeLa cells has been successfully achieved. Therefore, our FA-CPDs have potential applications as biocompatibility probes for cancer diagnosis and treatment.

Safety and Efficacy of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma (3-5 cm): a Propensity Score Matching Cohort Study.

BACKGROUND: We aim to investigate the safety and efficacy of radiofrequency ablation in the treatment of solitary hepatocellular carcinoma (3-5 cm) in comparison with surgical resection. METHODS: Included in this study were 388 patients with primary and solitary hepatocellular carcinoma, of whom 196 patients underwent surgical resection and the other 192 patients received radiofrequency ablation. Clinicopathological characteristics, prognosis, post-treatment complications, hospital stay, and financial expenditures between the two groups were compared retrospectively. RESULTS: The result of propensity score matching and subgroup analysis showed that the 1-, 3-, and 5-year overall survival and disease-free survival were comparable in patients with tumors of 3-4 cm in diameter between surgical resection and radiofrequency ablation groups. However, when the tumor size exceeded 4 cm in diameter, surgical resection exhibited a superior long-term prognosis compared with radiofrequency ablation. Nevertheless, hepatectomy was associated with high occurrences of postoperative complications, long hospital stay, and high hospitalization cost as compared with radiofrequency ablation. Further analysis of the relationship between tumor size and pathological features of hepatocellular carcinoma showed that tumors larger than 4 cm were positively correlated with a high rate of microvascular invasion and satellite nodule formation. CONCLUSION: For solitary hepatocellular carcinoma of 3-4 cm in diameter, radiofrequency ablation could achieve a comparable prognosis with a low incidence of post-treatment complications and low hospitalization costs, while surgical resection is recommended for solitary hepatocellular carcinoma tumors of 4-5 cm in diameter when long-term prognosis is considered.

Specific risk factors contributing to early and late recurrences of intrahepatic cholangiocarcinoma after curative resection.

BACKGROUND: Most intrahepatic cholangiocarcinoma (ICC) patients experienced tumor recurrences even after curative resection, but the optimal cut-off time point and the specific risk factors for early and late recurrences of ICC have not been clearly defined. The objective of the current study was to define specific risk factors for early and late recurrences of ICC after radical hepatectomy. METHODS: Included in this study were 259 ICC patients who underwent curative surgery at our hospital between January 2005 and December 2009. Recurrences in these patients were followed-up prospectively. Piecewise regression model and the minimum P value approach were used to estimate the optimal cut-off time point for early and late recurrences. Then, Cox's proportional hazards regression model was used to identify specific independent risk factors for early and late recurrences. RESULTS: Early and late recurrences occurred in 130 and 74 patients, respectively, and the 12th month was confirmed as the optimal cut-off time point for early and late recurrences. Cox's proportional hazards regression model showed that microvascular invasion (HR = 2.084, 95% CI 1.115-3.897, P = 0.021), multiple tumors (HR = 2.071, 95% CI 1.185-3.616, P = 0.010), abnormal elevation of serum CA19-9 (HR = 1.619, 95% CI 1.076-2.437, P = 0.021), and the negative hepatitis B status (HR = 1.650, 95% CI 1.123-2.427, P = 0.011) were independent risk factors for early recurrence, and HBV-DNA level > 106 IU/mL (HR = 1.785, 95% CI 1.015-3.141, P = 0.044) and a hepatolithiasis history (HR = 2.538, 95% CI 1.165-5.533, P = 0.010) contributed to late recurrence independently. CONCLUSION: Specific risk factors and mechanisms may relate to early and late recurrences of ICC after curative resection.

Coherent Precipitation and Strengthening in Compositionally Complex Alloys: A Review.

High-performance conventional engineering materials (including Al alloys, Mg alloys, Cu alloys, stainless steels, Ni superalloys, etc.) and newly-developed high entropy alloys are all compositionally-complex alloys (CCAs). In these CCA systems, the second-phase particles are generally precipitated in their solid-solution matrix, in which the precipitates are diverse and can result in different strengthening effects. The present work aims at generalizing the precipitation behavior and precipitation strengthening in CCAs comprehensively. First of all, the morphology evolution of second-phase particles and precipitation strengthening mechanisms are introduced. Then, the precipitation behaviors in diverse CCA systems are illustrated, especially the coherent precipitation. The relationship between the particle morphology and strengthening effectiveness is discussed. It is addressed that the challenge in the future is to design the stable coherent microstructure in different solid-solution matrices, which will be the most effective approach for the enhancement of alloy strength.

In vitro responses of bone-forming MC3T3-E1 pre-osteoblasts to biodegradable Mg-based bulk metallic glasses.

In light of the superior property profile of favorable biocompatibility, proper corrosion/degradation behavior and good mechanical properties, Mg-based bulk metallic glasses (BMGs) are considered as potential biodegradable biomaterials. In the present study, in vitro responses of bone-forming MC3T3-E1 pre-osteoblasts to Mg-Zn-Ca-Sr BMGs were studied in order to assess their feasibility to serve as orthopedic implants. The Mg-Zn-Ca-Sr BMGs were much more capable of supporting cell adhesion and spreading in comparison with crystalline AZ31B Mg alloy. The Mg-Zn-Ca-Sr BMG extracts showed no cytotoxicity to and slightly stimulated the proliferation of pre-osteoblasts. The cells cultured in 100% BMG extracts exhibited lower alkaline phosphatase activity as compared with that in negative control, which could be mainly ascribed to the inhibition of high concentrations of Zn ions on cell differentiation. With decreasing the extract concentration, the inhibitory effect was diminished and the 5% BMG extract exhibited slight stimulation in cell differentiation and mineralization. The high corrosion resistance of BMGs contributed to smaller environmental variations, compared with AZ31B alloy, thus lowering the unfavorable influences on cellular responses. A comparison among the biodegradable Mg-, Ca- and Sr-based BMGs for their biomedical applications is presented.

Value of counting positive PHH3 cells in the diagnosis of uterine smooth muscle tumors.

The diagnosis of uterine smooth muscle tumors including leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), bizarre (atypical) leiomyoma (BLM), mitotically active leiomyoma (MAL) and leiomyoma (LM) depends on a combination of microscopic features, such as mitoses, cytologic atypia, and coagulative tumor cell necrosis. However, a small number of these tumors still pose difficult diagnostic challenges. The assessment of accurate mitotic figures (MF) is one of the major parameters in the proper classification of uterine smooth muscle tumors. This assessment can be hampered by the presence of increased number of apoptotic bodies or pyknotic nuclei, which frequently mimic mitoses. Phospho-histone H3 (PHH3) is a recently described immunomarker specific for cells undergoing mitoses. In our study, we collected 132 cases of uterine smooth muscle tumors, including 26 LMSs, 16 STUMPs, 30 BLMs, 30 MALs and 30 LMs. We used mitosis specific marker PHH3 to count mitotic indexes (MI) of uterine smooth muscle tumors and compared with the mitotic indexes of hematoxylin and eosin (H&E). There is a positive correlation with the number of mitotic figures in H&E-stained sections and PHH3-stained sections (r=0.944, P<0.05). The ratio of PHH3-MI to H&E-MI has no statistically significant difference in each group except for LMs (P>0.05). The counting value of PHH3 in LMSs have significantly higher than STUMPs, BLMs, MALs and LMs (P<0.001) and the counting value of PHH3 is 1.5±0.5 times of the number of mitotic indexes in H&E. To conclude, our results show that counting PHH3 is a useful index in the diagnosis of uterine smooth muscle tumors and it can provide a more accurate index instead of the time-honored mitotic figure counts at a certain ratio.

Unclassified mixed germ cell-sex cord-stromal tumor with multiple malignant cellular elements in a young woman: a case report and review of the literature.

Unclassified mixed germ cell-sex cord-stromal tumor composed of germ cells and sex cord derivatives is a rare neoplasm. Approximately 10% of such tumors have malignant germ cell components. We report the case of a 28 year-old female with a right adnexal mass measuring 8 cm in greatest dimension, containing areas with both germ cell and sex cord components. The germ cell portion contained multiple growth patterns with a malignant appearance, while the sex cord element consisted mainly of annular tubules. Within the malignant germ cell elements was a dysgerminoma that accounted for approximately 75% of the tumor volume. Other malignant germ cell elements included yolk sac tumor, embryonal carcinoma, and choriocarcinoma, which comprised about 15% of the tumor volume. The annular tubule structures comprised about 10% of the total tumor volume. To our knowledge, this is the first case reported in the literature of an unclassified mixed germ cell-sex cord-stromal tumor associated with embryonal carcinoma components. The patient had a 46XX karyotype, regular menstrual periods, and no evidence of gross abnormalities in the contralateral ovary. The patient remained clinically well and disease-free 2 years after surgery. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed.

Low-grade endometrioid carcinoma of the ovary associated with undifferentiated carcinoma: case report and review of the literature.

The association of low-grade endometrioid carcinoma with undifferentiated carcinoma (UC) was first reported in endometrium carcinoma, termed with dedifferentiated carcinoma (DC). However, the coexistence of low-grade endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received minimal attention in ovary, and the behavior of this kind of neoplasm remains at further discussion. In this study, we reported a case of low-grade ovarian endometrioid carcinoma associated with UC and reviewed another four cases previously reported. We found a histological continuity between the LGEC and UC components in H&E section, which suggested a dedifferentiation from LGEC to UC components. In summary, this kind of pathological type has aggressive behavior and these patients have very poor prognosis regardless of the amount of undifferentiated carcinoma.