Primary leptomeningeal melanocytic neoplasms: A clinicopathologic, immunohistochemical, and molecular study of 12 cases.

This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence in-situ hybridization (including a 4-probe FISH assay with CDKN2A and MYC assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0-1%, IMC 0-3%, LMM 3-10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in GNAQ, GNA11, or PLCB4. Additional mutations of EIF1AX, SF3B1, or BAP1 were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. SF3B1 mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with SF3B1 mutation might be related to poor prognosis in LMN.

A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Prognostic value of the number of biopsied sentinel lymph nodes for Chinese patients with melanoma: A single-center retrospective study.

BACKGROUND: Sentinel lymph node biopsy (SLNB) helps to determine accurate pathological stages and facilitates strategies for regional disease control in melanoma. However, whether the number of biopsied sentinel lymph nodes (SLNs) influences the patients' survival is rarely investigated. METHODS: Acral or cutaneous melanoma patients with no history of nodal disease who received SLNB in Fudan University Shanghai Cancer Center (FUSCC) from January 1, 2017, to December 31, 2021 were retrospectively enrolled. Clinicopathological variables including Breslow index, ulceration, number of positive SLNs, SLN/non-SLN status were analyzed. The pathologic nodal (pN) stage and pathological stage were defined. RESULTS: A total of 381 eligible patients were enrolled in this study, of whom 132 (34.7%) patients were diagnosed with SLN-positive. The median number of biopsied SLNs was 2 (range: 1 to 20). Different numbers of biopsied SLNs did not influence the release-free survival (RFS) of the general patients. However, patients with >2 SLNs had a longer RFS than those with 1-2 SLNs in T4, N1a group and those who rejected complete lymph node dissection (CLND). CONCLUSIONS: In patients with T4 melanomas, N1a melanomas and those that did not undergo a CLND, the prognosis of those with three or more SLNs retrieved seemed to be improved.

Whole-exome sequencing reveals mutational profiles of anorectal and gynecological melanoma.

Mucosal melanoma is a rare and highly malignant type of melanoma. Among the sites that mucosal melanoma arises, anorectal and gynecological melanoma has more aggressive behavior and worse prognosis. There was no effective therapy for mucosal melanoma at present. Only a small number of mucosal melanoma patients which harbor mutations in BRAF or KIT benefit from targeted therapy. So it's an urgent need to identify more actionable mutations in mucosal melanoma. To identify more potential therapeutic targets in mucosal melanoma, 48 samples were collected from 44 patients with anorectal or gynecological melanoma and subjected to whole-exome sequencing. The tumor mutation burden was low with a median of 1.75 mutations per Mb. In chromosomal level, 1q, 6p and 8q of mucosal melanoma were significantly amplified while 9p, 10p, 10q, 16p and 16q were significantly deleted. Muc16 was the most frequently mutated oncogene in our samples(25%). The mutation frequency of KIT(20%) was comparable to the "triple-wild" genes-NRAS(20%), NF1(20%), and BRAF(11%). KMT2D mutation was found in 18.18% patients, which is previously unidentified. MAPK signaling pathway and lysine degradation were the most frequently mutated pathways. Moreover, patients with TP53 mutations tend to have worse clinical outcome (median survival time 19 vs. 50 months, log-rank P = 0.006). 2000 ore mutated genes involved in MAPK signaling pathway were identified, which expand the patients potentially benefit from ample MAPK inhibitors. KMT2D could be a potential therapeutic target. Moreover, TP53 could be a potential prognosis marker for mucosal melanoma.

Prediction of nonsentinel lymph node metastasis in acral melanoma with positive sentinel lymph nodes.

BACKGROUND: Metastasis in a nonsentinel lymph node (non-SLN) is an unfavorable independent prognostic factor in cutaneous melanoma (CM). Recent data did suggest potential value of completion lymph node dissection (CLND) in CM patients with non-SLN metastasis. Prediction of non-SLN metastasis assists clinicians in deciding on adjuvant therapy without CLND. We analyzed risk factors and developed a prediction model for non-SLN status in acral melanoma (AM). METHODS: This retrospective study enrolled 656 cases of melanoma who underwent sentinel lymph node biopsy at Fudan University Shanghai Cancer Center from 2009 to 2017. We identified 81 SLN + AM patients who underwent CLND. Clinicopathologic data, including SLN tumor burden and non-SLN status were examined with Cox and Logistics regression models. RESULTS: Ulceration, Clark level, number of deposits in the SLN (NumDep) and maximum size of deposits (MaxSize) are independent risk factors associated with non-SLN metastases. We developed a scoring system that combines ulceration, the cutoff values of Clark level V, MaxSize of 2 mm, and NumDep of 5 to predict non-SLN metastasis with an efficiency of 85.2% and 100% positive predictive value in the high-rank group (scores of 17-24). CONCLUSIONS: A scoring system that included ulceration, Clark level, MaxSize, and NumDep is reliable and effective for predicting non-SLN metastasis in SLN-positive AM.

Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi-institutional study.

PURPOSE: Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established. MATERIALS AND METHODS: We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022. RESULTS: Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first-line treatment was 18%. Three of the four patients with BRAF-mutated CM responded to dabrafenib and trametinib treatment. The median progression-free survival (PFS) and overall survival (OS) of first-line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver-directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites. CONCLUSION: CM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases.

Evaluation of the immunogenicity of a Crimean-Congo hemorrhagic fever virus vaccine candidate in mice developed based on a baculovirus Zera nanoparticle delivery system.

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease caused by Crimean-Congo hemorrhagic fever virus (CCHFV), which can cause severe clinical disease and even death in humans. In recent years, the disease has spread to a wider area, posing a major public health threat to China as well as the Middle East, Europe and Africa, and there is no safe and effective vaccine to prevent the disease. Recently, it has been shown that using the Zera fusion to target proteins can enhance immunogenicity and improve the potential for developing viral vaccines. Based on this finding, in this study, two vaccine candidates, Zera-Gn and Zera-Np, were prepared using an insect baculovirus system expressing CCHFV glycoprotein (Gn) and nucleocapsid protein (Np) fused with Zera tags, and evaluated for immunogenicity in BALB/c mice. The obtainedresults showed that both Zera-Gn and Zera-Np recombinant nanoparticles were successfully expressed, and Zera-Gn had good induction of humoral and cellular immunity in mice, and its immunogenicity was significantly higher than that of Zera-Np. The results indicated that Zera-Gn self-assembled nanoparticles prepared by fusing Zera tags with CCHFV spike-in protein Gn have the potential to be a candidate vaccine for CCHF, and this study provides a reference for the development of Zera self-assembled nanoparticle vaccine for CCHF.

Effects of different laying periods on airborne bacterial diversity and antibiotic resistance genes in layer hen houses.

Poultry farms are a complex environment for close contact between humans and animals. Accumulating evidence has indicated that pathogens and drug resistance genes in chicken houses may pose a serious threat to public health and economic concerns. However, insufficient knowledge of the indoor aerosol microbiome and resistome profiles of layer hen houses hampers the understanding of their health effects. Environmental surveillance of antibiotic resistance may contribute to a better understanding and management of the human exposure risk of bioaerosols under the environmental conditions of chicken houses. In addition, the chicken house has a long operation cycle, and the bacterial diversity and antibiotic resistance genes of aerosols in different periods may be different. In this study, air samples were collected from 18 chicken houses on three farms, including the early laying period (EL), peak laying period (PL), and late laying period (LL). 16S rRNA gene sequencing and metagenomics were used to study the composition of the bacteria and resistome in aerosols of layer hen houses and the results showed that they varied with laying period. The highest alpha diversity of bacteria was observed in PL bioaerosols. The dominant bacterial phyla included Firmicutes, Bacteroidetes and Proteobacteria. Three potential pathogenic bacterial genera (Bacteroides, Corynebacterium and Fusobacterium) were found. The most abundant ARG type was aminoglycosides in all laying periods. In total, 22 possible ARG host genera were detected. ARG subtypes and abundance were both higher in LL. Network analysis also showed higher co-occurrence patterns between the bacteria and resistome in bioaerosols. The laying period plays an important role in the bacterial community and resistome in layer house aerosols.

Pathogenicity and Transmissibility of Clade 2.3.4.4h H5N6 Avian Influenza Viruses in Mammals.

Avian influenza viruses (AIVs) have the potential for cross-species transmission and pandemics. In recent years, clade 2.3.4.4 H5N6 AIVs are prevalent in domestic poultry, posing a threat to the domestic poultry industry and public health. In this study, two strains of H5N6 AIVs were isolated from chickens in Hebei, China, in 2019: A/chicken/Hebei/HB1907/2019(H5N6) and A/chicken/Hebei/HB1905/2019(H5N6). Phylogenetic analysis showed that both viral HA genes clustered in the 2.3.4.4h clade. Receptor binding analysis showed that the HB1905 strain preferentially binds to α-2,3-linked sialic acid (SA) receptors, while the HB1907 strain preferentially binds to α-2,3- and α-2,6-linked sialic acid (SA) receptors. During early infection, the HB1907 strain is highly replicable in MDCK cells, more so than the HB1905 strain. Pathogenicity assays in mice showed that both viruses could replicate in the lungs without prior adaptation, with HB1907 being more highly pathogenic in mice than the HB1905 strain. Significantly, both the HB1905 and HB1907 strains can be transmitted through direct contact among guinea pigs, but the transmission efficiency of the HB1907 strain through contact between guinea pigs is much greater than that of the HB1905 strain. These results strengthen the need for ongoing surveillance and early warning of H5N6 AIVs in poultry.

Pathogenicity and Transmissibility of Goose-Origin H5N6 Avian Influenza Virus Clade 2.3.4.4h in Mammals.

Throughout the last decade, H5N6 avian influenza viruses (AIVs) circulating in poultry and infecting humans have caused increasing global concerns that they might become a pandemic threat to global health. Since AIVs could occasionally cause asymptomatic infections in geese, virus monitoring in such a host should be critical to the control of cross-species infection. In addition, previous studies showed that clade 2.3.4.4h H5N6 AIVs could infect mammals without adaptation. However, the pathogenicity and transmissibility of goose-origin clade 2.3.4.4h H5N6 AIVs in mammals remain unknown. In this study, two H5N6 AIVs were isolated from a domestic chicken (A/chicken/Hebei CK05/2019 (H5N6)) and a goose (A/goose/Hebei/GD07/2019(H5N6)). This study is the first to evaluate the pathogenicity and transmissibility of goose-origin clade 2.3.4.4h H5N6 AIVs in mammals by comparison with chicken-origin 2.3.4.4h H5N6 AIVs. The CK05 virus had an affinity for α-2,3-receptors, while the GD07 virus had an affinity for both α-2,3-and α-2,6-receptors. The GD07 virus had a higher replication capacity in vitro and more severe pathogenicity in mice than the CK05 virus. The CK05 virus could not be transmitted effectively among guinea pigs, whereas the GD07 virus could be transmitted through direct contact among guinea pigs. The results of this study indicated the potential health threat of clade 2.3.4.4h H5N6 AIVs to mammals and emphasized the importance of continuous monitoring of H5N6 AIVs, especially in waterfowl.

Metatranscriptomics Reveals the Diversity of the Tick Virome in Northwest China.

Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious diseases in humans or animals, potentially imposing significant public health burdens and threats to the husbandry industry. Therefore, identifying the profiles of tick-borne viruses will provide valuable information about the evolution and pathogen ecology of tick-borne viruses. In this study, we investigated the viromes of parasitic ticks collected from the body surfaces of herbivores in Xinjiang Uyghur Autonomous Region and Inner Mongolia Autonomous Region of China, two regions in northwest China. By using a metatranscriptomic approach, 17 RNA viruses with high diversity in genomic organization and evolution were identified. Among them, nine are proposed to be novel species. The classified viruses belonged to six viral families, including Phenuiviridae, Rhabdoviridae, Peribunyaviridae, Lispiviridae, Chuviridae, and Reoviridae, and unclassified viruses were also identified. In addition, although some viruses from different sampling locations shared significant similarities, the abundance and diversity of viruses notably varied among the different collection locations. This study demonstrates the diversity of tick-borne viruses in Xinjiang and Inner Mongolia and provides informative data for further study of the evolution and pathogenicity of these RNA viruses. IMPORTANCE Ticks are widely distributed in pastoral areas in northwestern China and act as vectors that carry and transmit a variety of pathogens, especially viruses. Our study revealed the diversity of tick viruses in Xinjiang and Inner Mongolia and uncovered the phylogenetic relationships of some RNA viruses, especially the important zoonotic tick-borne severe fever with thrombocytopenia syndrome virus in Inner Mongolia. These data suggest a complex and diverse evolutionary history and potential ecological factors associated with pathogenic viruses. The pathogenicity of these tick-borne viruses currently remains unclear. Therefore, future research should focus on evaluating the transmissability and pathogenicity of these tick-borne viruses.

Combination of Androgen Deprivation Therapy with Radical Local Therapy Versus Androgen Deprivation Therapy Alone for Newly Diagnosed Oligometastatic Prostate Cancer: A Phase II Randomized Controlled Trial.

BACKGROUND: Previous studies suggested that men with metastatic prostate cancer might benefit from local treatment of the primary tumor. OBJECTIVE: To determine whether radical local therapy (RLT) improves survival for men with oligometastatic prostate cancer (OMPCa). DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized controlled trial included patients with newly diagnosed OMPCa defined as five or fewer bone or extrapelvic lymph node metastases and no visceral metastases. INTERVENTION: Patients were randomly allocated to androgen deprivation therapy (ADT) or ADT and RLT. Men allocated RLT received either cytoreductive radical prostatectomy (RP) or prostate radiation therapy (RT) with a radical dose schedule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was radiographic progression-free survival (rPFS). Secondary outcomes were overall survival (OS) and prostate-specific antigen (PSA) progression-free survival. RESULTS AND LIMITATIONS: Between September 2015 and March 2019, 200 patients were randomized, with 100 men allocated to each group. The median age was 68 yr and the median PSA at diagnosis was 99 ng/ml. In the study group, 96 patients underwent RLT (85 RP and 11 RT). In the control group, 17 patients eventually received RLT (15 RP and two RT). All patients were included for an intention-to-treat analysis. After a median follow-up of -48 mo, the median rPFS was not reached in the study group and was 40 mo in the control group (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.27-0.70; p = 0.001). The 3-yr OS rate was 88% for the study group and 70% for the control group (HR 0.44, 95% CI 0.24-0.81; p = 0.008). CONCLUSIONS: Men with newly diagnosed OMPCa who received ADT plus RLT (mainly prostatectomy) had significantly higher rates of rPFS and OS than those who received ADT alone. PATIENT SUMMARY: This study investigated the effect of radical local therapy (RLT) of the primary tumor on survival in patents with oligometastatic prostate cancer. In our group, RLT improved radiographic progression-free and overall survival.

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center.

Background: Discrepancies in genetic alterations found in melanoma are conspicuous between different ethnic groups. With the approval of BRAF- and MEK-targeted inhibitors in China, it is necessary to further elucidate the landscape of gene mutation in Chinese melanoma patients. Methods: The frequency and distribution of BRAF, C-KIT, and NRAS mutations in 691 melanoma patients was determined, and the statistical significance of correlations between different gene mutations and clinicopathological features was analyzed. Results: Among a total of 691 patients, BRAF mutation was found in 166 patients (24.0%), and V600E was the prominent genetic alteration (145/166, 87.3%). Statistical analyses showed that younger patients (<60) had a higher BRAF mutation rate than older patients (≥60, P=0.000), and the frequency of BRAF mutation was more likely to be lower in patients with the following: melanoma located in an extremity (P=0.000), acral-lentiginous melanoma subtype (P=0.000), thinner melanoma thickness (P=0.047), and no ulceration (P=0.030). The frequency of NRAS mutation was 12.6% (38/302), and primarily involved codon 61 in exon 3 and codon 12 in exon 2. Mutation of C-KIT was detected in 65 patients (9.4%), and the most common site of mutations was L576 in exon 11 (29/65, 44.6%). Patients with NRAS or C-KIT mutation had higher Clark level (P=0.035 and 0.047, respectively) and were more likely to have melanoma located in an extremity (P=0.003 and 0.009, respectively) than those without such mutation. The concordance of gene mutations between paired primary and metastatic lesions was 89.6% (60/67), and visceral metastases showed the highest distribution of gene mutations versus primary melanomas (100.0%) compared with lymph nodes (90.9%) and cutaneous metastases (83.3%). Conclusions: In this large cohort of Chinese melanoma patients, the frequencies of BRAF and NRAS mutations were lower than those observed in Caucasian cohorts, but the clinicopathological features of BRAF, C-KIT, and NRAS mutation were consistent. Paired primary and metastatic lesions showed high concordance of gene mutations.

Presence of CD133-positive circulating tumor cells predicts worse progression-free survival in patients with metastatic castration-sensitive prostate cancer.

OBJECTIVE: To investigate the clinical significance of the expression of the stemness marker CD133 in circulating tumor cells of newly diagnosed metastatic castration-sensitive prostate cancer patients. METHODS: For this study, 104 metastatic castration-sensitive prostate cancer patients treated at the Fudan University Shanghai Cancer Center from September 2015 to February 2017 were considered. After enrollment, the patients received androgen deprivation therapy (bicalutamide + goserelin). Circulating tumor cells were isolated and identified using the CanPatrol system, which can identify not only traditional epithelial markers but also mesenchymal markers in cells that have undergone epithelial mesenchymal transition. CD133 was used to characterize the circulating tumor cells. The primary endpoint of this research was to evaluate progression to castration resistance. RESULTS: Among the 104 patients enrolled, 89 patients were circulating tumor cell positive at baseline, and the median circulating tumor cell count was four. The median follow-up was 24 months, and at the end of follow-up, the proportion of patients who progressed to castration-resistant prostate cancer in the CTC+CD133+ group was 93.3%, which was significantly higher than that of the circulating tumor cell negative group (73.3%) and the CTC+CD133- group (75.0%), with P = 0.043. After follow-up, progression-free survival for CTC+CD133+, CTC+CD133-, and circulating tumor cell patients was 10.0, 13.0, and 14.0 months, respectively, with P = 0.022. Univariate and multivariate analyses also confirmed that the characterization of circulating tumor cells using CD133 can independently predict progression-free survival in metastatic castration-sensitive prostate cancer patients after receiving androgen deprivation therapy (P = 0.042; hazard ratio 1.396). CONCLUSION: Baseline CTC+CD133+ was a poor independent prognostic factor for metastatic castration-sensitive prostate cancer patients to progress to castration-resistant prostate cancer after receiving androgen deprivation therapy.

Rapid detection of influenza A viruses using a real-time reverse transcription recombinase-aided amplification assay.

Introduction: Influenza A viruses (IAVs) are important pathogens of respiratory infections, causing not only seasonal influenza but also influenza pandemics and posing a global threat to public health. IAVs infection spreads rapidly, widely, and across species, causing huge losses, especially zoonotic IAVs infections that are more harmful. Fast and sensitive detection of IAVs is critical for controlling the spread of this disease. Methods: Here, a real-time reverse transcription recombinase-aided amplification (real-time RT-RAA) assay targeting conserved positions in the matrix protein gene (M gene) of IAVs, is successfully established to detect IAVs. The assay can be completed within 20 min at 42°C. Results: The sensitivity of the real-time RT-RAA assay was 142 copies per reaction at 95% probability, which was comparable to the sensitivity of the RT-qPCR assay. The specificity assay showed that the real-time RT-RAA assay was specific to IAVs, and there was no cross-reactivity with other important viruses. In addition, 100%concordance between the real-time RT-RAA and RT-qPCR assays was achieved after testing 120 clinical specimens. Discussion: The results suggested that the real-time RT-RAA assay we developed was a specific, sensitive and reliable diagnostic tool for the rapid detection of IAVs.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer.

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.

Preferentially expressed antigen in melanoma immunohistochemistry as an adjunct for differential diagnosis in acral lentiginous melanoma and acral nevi.

Preferentially expressed antigen in melanoma (PRAME) has shown promising utility in distinguishing benign melanocytic lesions from melanomas, but knowledge of its expression pattern in acral lentiginous melanoma (ALM) and acral nevi (ANs) is limited. Immunohistochemical expression of PRAME was examined in 75 ALMs and 34 ANs. The clinical and histopathologic characteristics of patients with ALM were collected. PRAME was immunoreactive in 89.3% (67/75) of ALMs, but entirely negative in 94.1% (32/34) of ANs. When staining at least 50% of lesional melanocytes was determined as positivity, the sensitivity and specificity of PRAME for distinguishing ALM from ANs were 69.3% and 100%, respectively. Seventy-one cases of ALMs had tumor cells in the epidermis; 71.8% (51/71) of them showed positive for PRAME. By contrast, 61 ALMs had tumor cells in the dermis; 65.6% (40/61) exhibited positive expression. Twenty-nine of 39 (74.4%) epithelioid cell ALMs were observed to be positive for PRAME. By comparison, 63.8% (23/36) of ALMs with spindle tumor cells were positive for PRAME. However, PRAME positive expression was not associated with any clinical and histopathologic characteristics of patients with ALM, including Breslow thickness, ulcer, cytomorphology, lymph node metastasis, or tumor-infiltrated lymphocytes (TILs). Nevertheless, we observed that 82.6% (19/23) of ALMs with lymph node involvement at diagnosis expressed PRAME, compared with 57.6% (20/35) of those without. In summary, PRAME immunohistochemistry can serve as a helpful adjunct in the differential diagnosis of ALMs and ANs with good sensitivity and high specificity. Additionally, PRAME tends to have a higher positive rate in epidermal melanocytes than in the dermis and is inclined to express in epithelioid cells than in spindle cells of ALMs.

High IL-23+ cells infiltration correlates with worse clinical outcomes and abiraterone effectiveness in patients with prostate cancer.

Individualized treatment of prostate cancer depends on an accurate stratification of patients who are sensitive to various treatments. Interleukin-23 (IL-23) was reported to play a significant role in prostate cancer. Here, we aimed to explore the clinical value of IL-23-secreting (IL-23+) cells in prostate cancer patients. We evaluated interleukin-23A (IL-23A) expression in The Cancer Genome Atlas database and retrospectively enrolled 179 treatment-naïve metastatic prostate cancer patients diagnosed in our institute between June 2012 and December 2014. IL-23+ cells were stained and evaluated via immunohistochemistry. Further, survival and multivariate Cox regression analyses were conducted to explore the prognostic value of IL-23+ cells. We found that IL-23A expression correlated with disease progression, while IL-23+ cells were clearly stained within prostate cancer tissue. Patients with higher Gleason scores and multiple metastatic lesions tended to have more IL-23+ cell infiltration. Further analyses showed that patients with higher levels of IL-23+ cells had significantly worse overall survival (hazard ratio [HR] = 2.996, 95% confidence interval [95% CI]: 1.812-4.955; P = 0.001) and a higher risk of developing castration resistance (HR = 2.725, 95% CI: 1.865-3.981; P = 0.001). Moreover, subgroup analyses showed that when patients progressed to a castration-resistant status, the prognostic value of IL-23+ cells was observed only in patients treated with abiraterone instead of docetaxel. Therefore, we showed that high IL-23+ cell infiltration is an independent prognosticator in patients with metastatic prostate cancer. IL-23+ cell infiltration may correlate with abiraterone effectiveness in castration-resistant prostate cancer patients.

Phylogenetic analysis of Crimean-Congo hemorrhagic fever virus in inner Mongolia, China.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne arbovirus that can cause bleeding and death in humans. The mortality rate in humans is between 5 and 30%. The pathogen is prevalent in more than 30 countries in the world. In China, the CCHFV has been reported in Xinjiang province but not in Inner Mongolia province yet. In this report, we phylogenetically analyzed a new CCHFV strain, HANM-18, identified from Hyalomma asiaticum and Hyalomma dromedarii collected in Alxa Left Banner and Alxa Right Banner of Inner Mongolia, China. Complete sequences of CCHFV were obtained by the nested PCR technique and used for phylogenetic analysis of the identity and evolutionary relationship with other CCHFV strains. Our results showed that the S and L fragments of the HANM-18 strain had a high percentage of identity with strains in Xinjiang, China. The M fragment was significantly homologous to South African isolates. In addition, these data also indicate that the HANM-18 strain may have been prevalent in northwestern Inner Mongolia for many years. This discovery will be helpful in CCHF prevention and control in Inner Mongolia, and it also adds new evidence to the epidemiology of CCHF in China.

Rh-endostatin combined with chemotherapy in patients with advanced or recurrent mucosal melanoma: retrospective analysis of real-world data.

BACKGROUND: Mucosal melanoma is rare and has distinct clinical and genetic features. Even with advances in targeted and immune therapies, the survival of patients with advanced or recurrent mucosal melanomas remains poor. The standard treatment remains controversial and we conducted this real-world study aimed to explore continuous intravenous recombinant human endostatin (Rh-endostatin) infusion plus chemotherapy in this population in the first-line setting. METHODS: Overall, 43 patients with advanced or recurrent mucosal melanoma treated at Fudan University Shanghai Cancer Center between April 2017 and August 2020 were retrospectively included. Patients received dacarbazine plus cisplatin or temozolomide plus cisplatin per the investigators' preference. Rh-endostatin (105 mg/m2) was administered with continuous infusion for 168 h (Civ 168 h). RESULTS: Of the 43 patients, 72.1% had metastatic disease, and the most common primary site was the gastrointestinal tract (51.2%). The most commonly observed mutations were NRAS (23.1%), BRAF (7.7%) and CKIT mutations (5.1%). An objective response was observed in 12 (30.0%) of the 40 evaluable patients, and disease control was achieved in 31 (77.5%) patients. With a median follow-up of 17.6 months, the median progression-free survival (PFS) and overall survival (OS) were 4.9 and 15.3 months, respectively. Additionally, high lymphocyte-to-monocyte ratio (LMR) (p = 0.023, HR 0.29, 95% CI: 0.10-0.84) and BRAF/KIT/RAS mutation (p = 0.028, HR 0.24, 95% CI: 0.07-0.86) were independently correlated with prolonged OS. Toxicity was manageable overall. CONCLUSION: Continuous Rh-endostatin infusion plus chemotherapy was effective and safe for the treatment of advanced or recurrent mucosal melanoma. High LMR was correlated with favorable PFS and OS in this patient population.