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Background Rearranged during transfection (RET) is a targetable oncogene. RET fusions have been reported in patients with metastatic colorectal cancer (mCRC). However, RET mutations in mCRC are less studied. Here, we aimed to characterize the clinical, pathological, and molecular landscape of RET‐mutated mCRC. Methods Five hundred and eighty‐two patients were included in this study. Next‐generation sequencing was performed to detect RET mutations and calculate tumor mutation burden (TMB). We compared the clinical, pathological, and molecular characteristics of mCRC cases with tumors that harbored somatic RET mutations (N = 16, 2.7%) or had wild‐type RET (N = 566, 97.3%). Results Males comprised the absolute majority of cases with RET mutations (15/16 [93.8%]) compared to their fraction among cases with wild‐type RET (339/566 [59.9%]). Furthermore, all patients with RET mutations were younger than 60 years (16/16 [100%]), whereas such patients were less predominant in the group with wild‐type RET (379/566 [67.0%]). Individuals with tumors positive for RET mutations more frequently exhibited mucinous histology (5/16 [31.2%] vs. 55/566 [9.7%]), exhibited a lower incidence of liver metastasis (4/16 [25.0%] vs. 335/566 [59.2%]), and higher incidence of peritoneal metastasis (9/16 [56.2%] vs.161/566 [28.4%]), expressed wild‐type TP53 (8/16 [50.0%] vs.120/566 [21.2%]), and showed an increased frequency of MSI‐high (6/16 [37.5%] vs. 18/566 [3.2%]). In those with microsatellite‐stable mCRC, patients with RET mutations had a higher median TMB than patients with wild‐type RET (9.4 vs. 6.7 mutations/Mb, respectively, p = 0.001). The median progression‐free survival was similar in individuals with mutated and wild‐type RET on the oxaliplatin‐based regimen (7.1 vs. 8.7 months, p = 0.516). Conclusions Our study suggests that cases with RET mutations represent a separate mCRC subtype. Further studies are needed to evaluate the efficacy of RET inhibitors in mCRC patients with RET mutations., RET mutations were enriched in male patients and those younger than 60 years.

Background: Recent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma. Methods: Two hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. Results: There were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p &lt, 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p &lt, 0.001) for DFS, and EGFR mutation type (p &lt, 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40, p = 0.036, TKIs vs. chemotherapy, HR = 0.38, p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22, p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42, p = 0.034, TKIs vs. chemotherapy, HR = 0.33, p &lt, 0.001) for DFS. No significant difference was found in the incidence of Grade 3–4 toxicities between groups (p = 0.445). Conclusions: Adjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

NanoKnife, a nonthermal ablation technique also termed irreversible electroporation (IRE), has been adopted in locally advanced pancreatic cancer (LAPC) treatment. However, reversible electroporation (RE) caused by heterogeneous electric field magnitude leads to inadequate ablation and tumor recurrence. Alphavirus M1 has been identified as a novel natural oncolytic virus which is nonpathogenic and with high tumor selectivity. This study evaluated improvements to therapeutic efficacy through combination therapy incorporating NanoKnife and M1 virus. We showed that IRE triggered reactive oxygen species (ROS)-dependent apoptosis in pancreatic cancer cells (PCCs) mediated by phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway suppression. When NanoKnife was combined with M1 virus, the therapeutic efficacy was synergistically enhanced. The combinatorial treatment further inhibited tumor proliferation and prolonged the survival of orthotopic pancreatic cancer (PC)-bearing immunocompetent mice. In depth, NanoKnife enhanced the oncolytic effect of M1 by promoting its infection. The combination turned immune-silent tumors into immune-inflamed tumors characterized by T cell activation. Clinicopathologic analysis of specific M1 oncolytic biomarkers indicated the potential of the combination regimen. The combinatorial therapy represents a promising therapeutic efficacy and may ultimately improve the prognosis of patients with LAPC.

Background To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC., Similar imaging features such as regional enlargement of the pancreas and delayed enhancement became a big challenge to differentiate focal‐type autoimmune pancreatitis (fAIP) from PDAC. In this study, we found that the pancreatic parenchyma of fAIP presented severe inflammation. Moreover, the mean relative computed tomography values of the pancreatic parenchyma were lower in fAIP than that in PDAC in all phases.

CHI3L2 (Chitinase-3-Like Protein 2) is a member of chitinase-like proteins (CLPs), which belong to the glycoside hydrolase 18 family. Its homologous gene, CHI3L1, has been extensively studied in various tumors and has been shown to be related to immune infiltration in breast cancer and glioblastoma. High CHI3L2 expression was reported to be associated with poor prognosis in breast cancer and renal cell carcinoma. However, the prognostic significance of CHI3L2 in glioma and its correlation between immune infiltration remains unclear. In this study, we examined 288 glioma samples by immunohistochemistry to find that CHI3L2 is expressed in tumor cells and macrophages in glioma tissues and highly expressed in glioblastoma and IDH wild-type gliomas. Relationships between CHI3L2 expression and clinical features (grade, age, Ki67 index, P53, PHH3 (mitotic figures), ATRX, TERTp, MGMTp, IDH, and 1p/19q co-deleted status) were evaluated. Kaplan-Meier survival was conducted to show high CHI3L2 expression in tumor cells (TC) and macrophage cells (MC) indicated poor prognosis in diffusely infiltrating glioma (DIG), lower-grade glioma (LGG), and IDH wild-type gliomas (IDH-wt). The overall survival time was higher in patients with dual-low CHI3L2 expression in TC and MC compared to those in patients with non-dual CHI3L2 expression and dual high expression in DIG and IDH wild-type gliomas. By univariate and multivariate analysis, we found that high CHI3L2 expression in tumor cells was an independent unfavorable prognostic factor in glioma patients. Moreover, we used two datasets (TCGA and CGGA) to verify the results of our study and explore the potential functional role of CHI3L2 by GO and KEGG analyses in gliomas. TIMER platform analysis indicated CHI3L2 expression was closely related to diverse marker genes of tumor immune infiltrating cells, including monocytes, TAMs, M1 macrophages, M2 macrophages, TGFβ1+ Treg and T cell exhaustion in GBM and LGG. Western Blot validated CHI3L2 is expressed in glioma cells and microglia cells. The results of flow cytometry showed that CHI3L2 induces the apoptosis of CD8+ T cells. In conclusion, these results demonstrate CHI3L2 is related to poor prognosis and immune infiltrates in gliomas, suggesting it may serve as a promising prognostic biomarker and represent a new target for glioma patients.

BackgroundProteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.MethodsThe genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.ResultsThe CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.ConclusionThis study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

To investigate the prognostic significance of time to recurrence (TTR) for overall survival (OS) and survival after recurrence (SAR) in patients with localized or regionally advanced cutaneous melanoma. A total of 731 cutaneous melanoma patients with an initial diagnosis of 8th American Joint Committee on Cancer (AJCC) clinical stage I‐III were included in this study. The prognostic factors associated with OS and SAR were estimated through Kaplan‐Meier and Cox regression analysis. Of the total cohort, 329 patients (45%) died, and 418 patients (57%) experienced recurrence. The median follow‐up and TTR were 55.6 months and 9.6 months, respectively. A total of 141 patients (19%) experienced recurrence in

Central nervous system (CNS) embryonal tumors (WHO grade IV) are a heterogeneous group of rare, poorly differentiated neuroepithelial malignant neoplasms that commonly occur in children, and they have a poor prognosis. The 2016 WHO (World Health Organization) classification of CNS tumors created a major shift in paradigm of the classification of embryonal tumors. However, some cases were still difficult to classify. Further integrative genomic analysis is needed to improve the precise classification, diagnosis and treatment of CNS embryonal tumors. Herein, we firstly report a case of CNS embryonal tumor harboring the pathogenic CIC–LEUTX gene fusion. A 2-year-old male infant presented with a solid cystic mass in the left temporal lobe-basal ganglia and left parietal lobe (maximum diameter, 75 mm) and underwent gross tumor resection. The tumor was classified as a poorly differentiated embryonal neoplasm of neuroectodermal origin that lacked specific features and rosettes. By immunohistochemistry, the tumor cells were strongly positive for synaptophysin, and the Ki67 proliferation index was high (>50%). FISH (Fluorescence in situ hybridization) results indicated no change in the copy number at the 19q13.42 C19MC locus. Next generation sequencing showed a CIC–LEUTX gene fusion, a somatic TSC2 c.G2714A mutation, and a heterozygous germline NBN c.C127T mutation. One month after surgery, there was recurrence of the intracranial tumor (maximum diameter, 55 mm) as well as spinal cord implantation metastasis. The patient received chemotherapy (CTX+CBP+VCR/DDP+VP-16), radiotherapy, and a drug targeting the TSC2 gene (everolimus). At the time of this writing, the patient is alive without evidence of disease for 11 months. This is the first report of the CIC–LEUTX gene fusion in a case of CNS embryonal tumor.

Background CMTM6 is a novel key regulator of PD-L1. High expression of both CMTM6 and PD-L1 may predict the benefit of PD-1 axis blockade in lung cancer. We aimed to investigate the expression pattern of CMTM6 between mismatch repair-defective (dMMR) and mismatch repair-proficient (pMMR) colorectal cancer (CRC) tissues and assess its correlation with the response to PD-1/PD-L1 pathway blockade. Methods Immunohistochemistry (IHC) was used to analyze CMTM6 and PD-L1 expression and immune cell density in dMMR/pMMR CRC. Quantitative multiplex immunofluorescence (IF) was performed to detect CMTM6, PD-L1, CD4, CD8, CD68 and CD163 expression in CRC patients treated with PD-1/PD-L1 inhibitors. Result IHC analysis showed that CMTM6 and PD-L1 were both expressed in tumor cells (TCs) and invasion front immune cells (ICs). CMTM6 and PD-L1 expression and CD4+, CD8+, CD68+ or CD163+ cell density were significantly higher in dMMR CRC patients than in pMMR CRC patients. CMTM6 expression was positively correlated with PD-L1 expression and CD163+ M2 macrophage density in dMMR CRC. IF analysis showed that the coexpression rate of CMTM6/PD-L1 and the expression rate of CMTM6 in CD8+ T cells and CD163+ M2 macrophages were significantly increased in the group that exhibited clinical benefit. CMTM6 expression in M2 macrophages was identified as the best biomarker for predicting the responsiveness to PD-1/PD-L1 inhibitors. Conclusions CMTM6 expression in M2 macrophages may predict the PD-1/PD-L1 inhibitor response rate in CRC patients more accurately than dMMR/microsatellite instability-high (MSI-H) status. It can also identify pMMR CRC patients who could benefit from PD-1/PD-L1 inhibitors.

Purpose: To investigate the predictive values of plasma Epstein-Barr Virus (EBV)- deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC).Patients and Methods: Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre- and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival.Results: A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment (N = 66), post-treatment (N = 93) and/or during follow-up (N = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ≤ 10,000 copies/mL, 37.2 vs. 75.1%, p = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, p < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52–7.78; p = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8–99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ≤ 1,000 copies/mL, 72.9 vs. 100%, p < 0.001).Conclusions: Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.

Background Understanding the molecular landscape of glioblastoma (GBM) is increasingly crucial for its therapy. Immune checkpoint molecules motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecule T cell immunoglobulin mucin-3 (Tim-3) on tumor-infiltrating immune cells (TIICs) and O-6-Methylguanine-DNA methyltransferase (MGMT) methylation status remains to be fully elucidated. We aimed to develop an MGMT methylation status-associated immune prognostic signature for predicting prognosis in GBMs.Patients and Methods: A total of 84 patients with newly diagnosed GBM were involved. MGMT methylation status was retrospectively analyzed and the expression level of Tim-3 protein was investigated using immunohistochemistry (IHC). The correlation between Tim-3 protein expression and MGMT methylation status, and the prognosis was explored.Results The obtained data showed that Tim-3 protein was expressed at different levels in GBMs. Mesenchymal expression of Tim-3 protein in these tissues was 73.81% (62/84), including low 15.48% (13/84), moderate 7.14% (6/84) and strong expression 51.19% (43/84), respectively. Of the 48 patients whose tumors tested positive for MGMT methylation, the remaining 36 patients was negative.Conclusions We profiled the immune status in GBM with MGMT promoter methylation and established a local immune signature for GBM, which could independently identify patients with a favorable prognosis, indicating the relationship between prognosis and immune. MGMT promoter methylation with lower Tim-3 protein expression was statistically significantly associated with better survival.

To evaluate the diagnostic potential of intravoxel incoherent motion (IVIM) DWI for differentiating metastatic and non-metastatic lymph node stations (LNS) in pancreatic ductal adenocarcinoma (PDAC). 59 LNS histologically diagnosed following surgical resection from 15 patients were included. IVIM DWI with 12 b values was added to the standard MRI protocol. Evaluation of parameters was performed pre-operatively and included the apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f). Diagnostic performance of ADC, D, D* and f for differentiating between metastatic and non-metastatic LNS was evaluated using ROC analysis. Metastatic LNS had significantly lower D, D*, f and ADC values than the non-metastatic LNS (p< 0.01). The best diagnostic performance was found in D, with an area under the ROC curve of 0.979, while the area under the ROC curve values of D*, f and ADC were 0.867, 0.855 and 0.940, respectively. The optimal cut-off values for distinguishing metastatic and non-metastatic lymph nodes were D = 1.180 × 10−3 mm2/s; D* = 14.750 × 10−3 mm2/s, f = 20.65 %, and ADC = 1.390 × 10−3 mm2/s. IVIM DWI is useful for differentiating between metastatic and non-metastatic LNS in PDAC. • IVIM DWI is feasible for diagnosing LN metastasis in PDAC. • Metastatic LNS has lower D, D*, f, ADC values than non-metastatic LNS. • D-value from IVIM model has best diagnostic performance, followed by ADC value. • D* has the lowest AUC value.

INTRODUCTION Central nervous system (CNS) embryonal tumor is a group of rare, poorly differentiated neuroepithelial malignant neoplasm predominantly occurs in pediatrics. Herein, we firstly report a CNS embryonal tumor harboring pathogenic CIC-LEUTX fusion. METHODS Immunohistochemistry (IHC), Fluorescence in Situ Hybridization (FISH) and Next Generation sequencing (NGS). RESULTS A 2-year-old male was found to have solid and cystic mass in left temporal lobe-basal ganglia and left parietal lobe (maximum diameter=75mm). The pathological diagnosis was CNS embryonal tumor (NEC) after totally resection. The tumor was poorly differentiated embryonal neoplasms of neuroectodermal origin that lacked the specific features and rosettes. IHC showed Syn was strongly/diffusely positive and Ki67 proliferation index was high (50%+), and copy number at the 19q13.42 C19MC locus showed no alterations. NGS showed pathogenic mutations including a brand new CIC-LEUTX fusion, heterozygous germline NBN c.C127T mutation and somatic TSC2 c.G2714A mutation. One month after operation, intracranial tumor recurred (maximum diameter=55mm) and spinal cord implantation metastasis occurred, and then the patient received chemotherapy (CTX+CBP+VCR/DDP+VP-16) and had significant improvement in symptoms and tumor shrinkage (maximum diameter=31mm). Literature review revealed CIC fusion predominantly presented in sarcomas, such as CIC-NUTM1 fusion in rare CNS sarcoma, CIC-LEUTX fusion in epithelioid angiosarcoma and CIC-DUX4 fusion in Ewing-like sarcoma. Hitherto, apart from this case, there were only two cases which had CIC-LEUTX fusion in CNS, including a case of CNS angiosarcoma and a case of anaplastic ganglioglioma. CONCLUSIONS We firstly found a specific new type in CNS embryonal tumor with distinct molecular-pathological characteristics of CIC-LEUTX fusion.

e22003 Background: Medical advances have been greatly improved in the survival rate for Wilms’ tumor, but the survival is still dismal for relapsed/refractory (R/R) patients. In the present study, we aimed to investigated the genomic profiling and the incidence of germline cancer susceptibility mutations of Chinese patients with R/R WT. Methods: From Jun 18, 2020 to Dec 22, 2020, the tumor specimens with matched blood samples obtained from R/R pediatric WT in Sun Yat-Sen University Cancer Center were performed next-generation sequencing (NGS) using a 539 cancer-related gene panel in a CAP-certified laboratory (Simcere Diagnostic Co, Ltd). Clinical information including age, gender and tumor histology were collected. Somatic and germline variations including single nucleotide variants (SNV), insertion-deletion variants (Indels), copy number variations (CNVs) and fusion, as well as tumor mutational burden (TMB)/microsatellite instability (MSI) were analyzed. IHC staining for PD-L1 expression was performed by FDA-approved VENTANA PD-L1(SP263) assay. Results: Eight patients with R/R WT were enrolled in this study, including 5 males and 3 females, with a median age of 6 years old (range, 3-14). All of the pathology was identified as favorable histology WT (FHWT). Of the specimens, 8 were from pulmonary and 1from peritoneum. We identified 152 reportable molecular aberrations, with a median of 19 (0-24). CNVs accounted for the majority of the total somatic aberrations, followed by SNVs, the percentage was 77% and 22%, respectively. Genes with either CNVs or SNVs were detected in FGFR1 (n=4), ERBB2(n=3), MYCN(n=4), MET(n=2), CDK4/6(n=2), TP53(n=2), CTNNB1(n=2), MYC(n=2), NF1(n=2), MDM4(n=2), CHEK2(n=1), FBXW7(n=1), EGFR(n=1). Notable cancer driver mutations were also characterized, such as the amplifications of ERBB2/MET/EGFR/FGFR1, and the point variations of CHEK2/FBXW7/NF1. Besides, a novel ASB12 intergenic region- AMER1 fusion was identified. Both of the patients available for PD-L1 evaluation showed negative PD-L1 expression on tumor cells. The median TMB was 1.47 (range, 0-7.8). All patients were microsatellite stabilization (MSS). A 4-year-old patient suffering peritoneal relapse harbored a germline pathogenic mutation in FANCA (c.1777-1G>C, intron 19), this locus has never been reported in WT before. Conclusions: We discovered some driver genes mutations which potentially sensitive to the corresponding targeted drugs in Chinese R/R WT patients. Large sample size was needed to provide a better understanding of molecular features in R/R WT patients to achieve precision medicine.

H3 K27M-mutant diffuse midline gliomas are associated with worse prognosis than H3 K27M wild-type gliomas. In the present study, we sought to evaluate the conventional magnetic resonance imaging (cMRI) of H3 K27M-mutant glioma and examine whether diffusion-weighted imaging (DWI) derived apparent diffusion coefficient (ADC) could noninvasively predict H3 K27M mutational status in brain diffuse midline gliomas.The institutional review board approved this study and waived the requirement for informed consent. Thirty-eight patients with brain diffuse midline gliomas were retrospectively reviewed. The parameters of preoperative cMRI were evaluated. The minimal ADC, peritumoral ADC, ratio of minimal ADC, and ratio of peritumoral ADC were measured, and significant differences between the two groups were identified by logistic regression analysis adjusted for age and tumor location. Receiver operating characteristic curves and logistic regression analysis adjusted for age and tumor location were used to assess the diagnostic performances of the minimal ADC, peritumoral ADC, ratio of minimal ADC, and ratio of peritumoral ADC.H3 K27M-mutant gliomas in different locations have diverse imaging characteristics. Minimal ADC, peritumoral ADC, ratio of minimal ADC, and ratio of peritumoral ADC values were significantly lower in the H3 K27M-mutant gliomas than in the wild-type gliomas (P 0.05). The combination of ratio of minimal ADC and ratio of peritumoral ADC provided the largest area under the curve (AUC) of 0.872 in defining H3 K27M-mutational status.The combination of ratio of minimal ADC and ratio of peritumoral ADC can noninvasively detect the H3 K27M mutational status in brain diffuse midline gliomas.

The aim of this study is to establish and validate an effective prognostic nomogram in patients with AFP-negative hepatocellular carcinoma (HCC). The nomogram was based on a primary cohort that consisted of 419 patients with clinicopathologically diagnosed with HCC, all the data was gathered from 2008 to 2014 in Sun Yat-sen University Cancer Center. All the model factors were determined by univariate and multivariate Cox hazard analysis. The concordance index (C-index) and calibration curve were used to determine the predictive accuracy and discriminative ability of the nomogram, and compared with the TNM staging systems on HCC. Internal validation was assessed. An independent validation cohort contained 150 continuous patients from 2014 to 2015. Independent factors for overall survival (OS) were body mass index (BMI), tumor stage, distant metastases, HBs Ag, lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), and albumin (ALB), which were all contained into the nomogram. The calibration curve for probability of OS showed good agreement between prediction by nomogram and actual observation. The C-index of nomogram was 0.807 (95% CI: 0.770-0.844), which was superior to the C-index of AJCC TNM Stage (0.697). The AUC was 0.809(95%CI: 0.762-0.857). In the validation cohort, the nomogram still gave good discrimination (C-index: 0.866, 95% CI: 00.796-0.936; AUC: 0.832, 95%CI: 0.747-0.917) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and a high risk group, respectively. The proposed nomogram presents more accurate and useful prognostic prediction for patients with AFP-negative HCC.

Background The neuronal intermediate filament alpha-internexin (α-internexin) is a cytoskeleton protein which is involved in the tumor initiation and progression. In this study, we examined the expression and prognosis value of α-internexin in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Methods α-internexin was detected with immunohistochemical staining in 286 tumor specimens from patients with GEP-NENs. Methylation status of α-internexin was evaluated by bisulfite genomic sequencing. We assessed the prognostic value of α-internexin and its correlation with relevant clinicalpathological characteristics. Results The reduced/loss of expression rate of α-internexin in GEP-NEN was 73.4% (210/286), while the positive expression rate was 26.6% (76/286). The difference of α-internexin deficiency was not statistically significant between gastrointestinal NENs (GI-NENs) and pancreatic NENs (pNENs). However, we found significant difference of reduced/loss of α-internexin expression among different sites of GI-NENs (χ2 = 43.470, P

Purpose To explore the role of CD15 expression in the prognosis of clear cell renal cell carcinoma (ccRCC) in Chinese patients. Methods The study included 301 patients who had undergone surgery for localized ccRCC. All paraffin-embedded tumor sections were collected to make a set of tissue microarrays. CD15 expression was assessed by immunohistochemistry. The relationship between CD15 expression and survival parameters, clinicopathology features was assessed. Kaplan-Meier and Cox proportional hazards model were utilized to determine the correlation between CD15 expression and overall survival (OS). Results The median follow-up time was 54.6 months (range, 3-121 months). The positive rate of CD15 expression was 81.7% (246/301). The cut-off value of CD15 expression was defined as the maximum for Youden index by plotting the receiver operating characteristic curve for survival status. As the threshold was 0.5, all cases were divided into two groups: positive expression group and negative expression group. In correlation analysis, loss of CD15 expression was correlated with female gender, higher Fuhrman nuclear grade, with sarcomatoid differentiation, with necrosis, and with vascular invasion. Kaplan-Meier analysis indicated that the OS time of patients with loss of CD15 expression was shorter than that of patients with positive CD15 expression (P = 0.013). Conclusion CD15 is a significant prognostic factor in clear cell renal cell carcinoma.

Aim To evaluate the prognostic value of imaging patterns in combined hepatocellular-cholangiocarcinoma. Materials and methods A total of 36 patients with histopathologically confirmed combined hepatocellular-cholangiocarcinoma were enrolled. Pretreatment imaging was conducted to evaluate the tumour enhancement patterns, based on which the disease was classified as two subtypes: radiographic hepatocellular carcinoma-dominant ( n =26) and radiographic cholangiocarcinoma-dominant ( n =10). Moreover, based on the proportion of components, all combined hepatocellular-cholangiocarcinoma cases were divided into histopathological hepatocellular carcinoma-dominant ( n =26) or histopathological cholangiocarcinoma-dominant ( n =10). The Kaplan–Meier method was used to compare patient outcome between the two subtypes of each classification. Univariate Cox regression analysis were employed to evaluate the prognostic relevance of the imaging and histopathological classification. Results Consistency between histopathological and imaging classification was not high. Only 66.7% of patients had consistent classification. Moreover, the median overall survival of the radiographic cholangiocarcinoma-dominant and radiographic hepatocellular carcinoma-dominant population was 15.03 and 40.4 months, respectively ( p =0.012); however, no significant difference was observed between histopathological type, with median overall survival being 32.07 and 40.4 months in the histopathological cholangiocarcinoma-dominant group and histopathological hepatocellular carcinoma-dominant group, respectively ( p =0.784). Conclusion There was an association between imaging patterns and overall survival in combined hepatocellular-cholangiocarcinoma. Postoperative re-evaluation of imaging patterns could help to assess patient outcome.

In histopathology images, there often exists several Nuclei overlapped with each other which causes difficulty to automatic nuclei segmentation. As we all know, watershed algorithm has been widely employed in image segmentation. But the limitation of watershed segmentation is sensitive to noise and can lead to serious over-segmentation. In this paper, we present an improved watershed transformation that incorporates opening-closing reconstruction and the distance transform with chamfer algorithm after color deconvolution, and H-minima . Unlike the classical watershed segmentation algorithm our improved method is able to resolve oversegmentation. The experiment results demonstrate our method successfully segment out each nuclei on breast cancer histology images, effectively address over-segmentation existed in traditional watershed segmentation , and preserve the original edges of each nuclei in the image completely.

CPEB4 plays an important role in cancer progression. However, the clinicopathological significance of CPEB4 expression to glioma and its expression levels in glioma tissues and cell lines are unknown. The present study investigated the potential prognostic value of CPEB4 for human glioma. Immunohistochemistry (IHC) was performed to examine the dynamics of CPEB4 expression in glioma and nonneoplastic brain tissues, and the expression of CPEB4 in cell lines and freshly prepared tissue samples was measured using Western blotting and real-time PCR. CPEB4 was highly expressed at the mRNA and protein levels in 4 glioma cell lines and in 4 freshly prepared glioma tissues. Immunohistochemical analysis demonstrated that CPEB4 expression in glioma tissue was higher than that in corresponding nonneoplastic brain tissue (P