Heterogeneity of Hippo signalling activity in different histopathologic subtypes of renal cell carcinoma.

This study aimed to reveal the prognostic role of the Hippo pathway in different histopathological subtypes of renal cell carcinoma (RCC). The TCGA-KIRC (n = 537), TCGA-KIRP (n = 291) and TCGA-KICH (n = 113), which contain data about clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC), respectively, were investigated. Gene Set Variation Analysis was used to compare the activity of many pathways within a single sample. Oncogenic pathway-related expression differed between cases of ccRCC involving low and high Hippo pathway activity. There were two subsets of ccRCC, in which the cancer exhibited lower and higher Hippo signalling activity, respectively, compared with normal tissue. In the ccRCC cohort, lower Hippo pathway activity was associated with a higher clinical stage (p < 0.001). The Hippo pathway (HR = 0.29; 95% CI = 0.17-0.50, p < 0.001), apoptosis (HR = 6.02; 95% CI = 1.47-24.61; p = 0.013) and the p53 pathway (HR = 0.09; 95% CI = 0.02-0.36; p < 0.001) were identified as independent prognostic factors for ccRCC. The 5-year overall survival of the ccRCC patients with low and high Hippo pathway activity were 51.9% (95% CI = 45.0-59.9) and 73.6% (95% CI = 67.8-79.9), respectively. In conclusion, the Hippo pathway plays an important role in the progression of ccRCC. Low Hippo pathway activity is associated with poor outcomes in ccRCC, indicating the tumour suppressor function of this pathway.

Investigating the role of core needle biopsy in evaluating tumor-stroma ratio (TSR) of invasive breast cancer: a retrospective study.

PURPOSE: Tumor-stroma ratio (TSR) of invasive breast carcinoma has gained attention in recent years due to its prognostic significance. Previous studies showed TSR is a potential biomarker for indicating the tumor response to neoadjuvant chemotherapy. However, it is not clear how well TSR evaluation in biopsy specimens might reflect the TSR in resection specimens. We conducted a study to investigate whether biopsy evaluation of TSR can be an alternative method. METHOD: We collected cases with invasive breast carcinoma of no special type (IBC-NST) from University of Yamanashi hospital between 2011 and 2017 whose biopsy and resection specimens both had a pathologically diagnosis of IBC-NST (n = 146). We conceptualized a method for evaluating TSR in biopsy specimens within a preliminary cohort (n = 50). Within the studied cohort (n = 96), biopsy-based TSR (b-TSR) and resection-based TSR (r-TSR) were scored by two pathologists. We then evaluated our method's validity and performance by measuring interobserver variability between the two pathologists, Spearman's correlation between b-TSR and r-TSR, and the receiver operating characteristics (ROC) analysis for defining stroma-rich and stroma-poor tumors. RESULTS: Intra-class coefficient between the two pathologists was 0.59. The correlation coefficients between b-TSR and r-TSR in the two pathologists were 0.45 and 0.37. The ROC areas under the curve were 0.7 and 0.67. By considering an r-TSR of < 50% as stroma-rich, the sensitivity and specificity of detecting stroma-rich tumors were 64.1% and 66.7%, respectively, when b-TSR was < 40%. CONCLUSION: Our current b-TSR evaluation method can provide information about r-TSR and facilitate pre-treatment therapy follow-up.

Association of Circadian Clock Gene Expression with Pediatric/Adolescent Asthma and Its Comorbidities.

The pathology of asthma is characterized by marked day-night variation, which is likely controlled by circadian clock activity. This study aimed to clarify the association of core circadian clock gene expression with clinical features of asthma. For this purpose, we accessed the National Center for Biotechnology Information database and analyzed transcriptomes of peripheral blood mononuclear cells and clinical characteristics of 134 pediatric/adolescent patients with asthma. Based on the expression patterns of seven core circadian clock genes (CLOCK, BMAL1, PER1-3, CRY1-2), we identified three circadian clusters (CCs) with distinct comorbidities and transcriptomic expressions. In the three CC subtypes, allergic rhinitis, and atopic dermatitis, both asthma comorbidities occurred in different proportions: CC1 had a high proportion of allergic rhinitis and atopic dermatitis; CC2 had a high proportion of atopic dermatitis but a low proportion of allergic rhinitis; and CC3 had a high proportion of allergic rhinitis but a low proportion of atopic dermatitis. This might be associated with the low activity of the FcεRI signaling pathway in CC2 and the cytokine-cytokine receptor interaction pathways in CC3. This is the first report to consider circadian clock gene expression in subcategories of patients with asthma and to explore their contribution to pathophysiology and comorbidity.

High-grade uterine sarcoma with osteosarcomatous differentiation arising from a MED12-mutated leiomyoma, a case report.

Uterine osteosarcoma has been reported, but it is an extremely rare tumor with highly aggressive behavior and poor prognosis. The pathogenesis of uterine osteosarcoma is not fully understood. Herein, we report on a high-grade uterine sarcoma with focal osteosarcomatous differentiation that developed from a long-standing MED12-mutated leiomyoma. A 47-year-old nulligravida woman, with known uterine leiomyoma presented with abdominal pain and distention. Imaging analyses revealed a tumor with a large cystic area in the uterine corpus and multiple metastases in intrapelvic and paraaortic lymph nodes, left ovary and left lung. With a clinical diagnosis of uterine sarcoma the patient underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and removal of the left obturator lymph node. Despite postoperative chemotherapy and radiation therapy, the tumor progressed rapidly. She died 18 weeks after the surgery. Histopathologic examination identified a high-grade pleomorphic sarcoma in which focal osteoid production was observed. This high-grade sarcoma with focal osteosarcomatous differentiation was located within the uterine leiomyoma, and Sanger sequencing showed the identical MED12 L36R mutation in both the osteosarcomatous and leiomyomatous components supporting the shared origin of these two components. We, therefore, concluded that the high-grade sarcoma with osteosarcomatous differentiation arose from the transformation of the precedent leiomyoma.

Immunohistochemical detection of cancer genetic abnormalities.

New applications of immunohistochemistry (IHC) expand rapidly due to the development of molecular analyses and an increased understanding of molecular biology. IHC becomes much more important as a screening or even a confirmatory test for molecular changes in cancer. The past decades have witnessed the release of many immunohistochemical markers of the new generation. The novel markers have extensively high specificity and sensitivity for the detection of genetic abnormalities. In addition to diagnostic utility, IHC has been validated to be a practical tool in terms of treatments, especially molecular targeted therapy. In this review, we first describe the common alterations of protein IHC staining in human cancer: overexpression, underexpression, or loss of expression and altered staining pattern. Next, we examine the relationship between staining patterns and genetic aberrations regarding both conventional and novel IHC markers. We also mention current mutant-specific and fusion-specific antibodies and their concordance with molecular techniques. We then describe the basic molecular mechanisms from genetic events to corresponding protein expression patterns (membranous, cytoplasmic, or nuclear patterns). Finally, we shortly discuss the applications of immunohistochemistry in molecular targeted therapy. IHC markers can serve as a complementary or companion diagnostic test to provide valuable information for targeted therapy. Moreover, immunohistochemistry is also crucial as a companion diagnostic test in immunotherapy. The increased number of IHC novel antibodies is broadening its application in anti-cancer therapies.

Comprehensive analysis of distinct circadian clock subtypes of adult diffuse glioma and their associations with clinicopathological, genetic, and epigenetic profiles.

The circadian clock (CC) has biological and clinical implications in gliomas. Most studies focused on CC effects on the tumor microenvironment and the application of chronotherapy. The present study focused on CC gene expression patterns and intracellular oncogenic activities. Glioma gene expression data were collected from The Human Cancer Genome Atlas (TCGA) project. After applying inclusion and exclusion criteria, we selected 666 patients from TCGA-GBM and TCGA-LGG projects and included important clinicopathological variables. The entire cohort was subjected to clustering analysis and divided into CC1 and CC2 subtypes based on statistical, biological, and clinical criteria. CC2 gliomas showed higher expression of BMAL1 and CRY1 and lower expression of CRY2 and PER2 (adjusted P < .001). CC2 gliomas had q higher activity of cell proliferation, metabolic reprogramming, angiogenesis, hypoxia, and many oncogenic signals (P < .001). The CC2 subtype contained a higher proportion of glioblastomas (P < .001) and had a worse prognosis (P < .001). Stratified Kaplan-Meier and multivariable Cox analyses illustrated that the CC subtype is an independent prognostic factor to clinicopathological characteristics (P < .001), genetic aberrations (P = .006), and biological processes (P < .001). Thus, this study shows statistical evidence of CC subtypes and their biological, and clinicopathological significance in adult gliomas.

Molecular and clinicopathological features of granzyme B-negative extranodal NK/T-cell lymphoma.

Extranodal NK/T-cell lymphoma (ENKTL) generally expresses cytotoxic molecules, including granzyme B (GZMB), T-cell-restricted intracellular antigen-1 (TIA-1), and perforin; however, the expression of these molecules varies across cases. We performed gene expression profiling and identified unique biological and clinicopathological features of GZMB-negative ENKTL. We reviewed the clinicopathological characteristics of 71 ENKTL samples. Gene expression profiling on nine ENKTLs using multiplexed, direct, and digital mRNA quantification divided ENKTLs into Groups A (n = 7) and B (n = 2) through hierarchical clustering and t-distributed stochastic neighbor embedding. Group B was characterized by downregulation of genes associated with IL6-JAK-STAT3 signaling and inflammatory responses. GZMB mRNA expression was significantly downregulated in Group B. GZMB protein expression was evaluated with immunohistochemistry in all 71 ENKTLs, and expression data of Tyr705-phosphorylated STAT3 (pSTAT3) and MYC from our previous study was utilized. T-cell receptor gamma (TRG) gene rearrangement in the selected samples was also assessed using PCR. GZMB expression was higher in pSTAT3-positive (p = 0.028) and MYC-positive (p = 0.014) ENKTLs. Eighteen percent (13/71) of all ENKTLs were negative for GZMB (defined by positivity <10 %); patients with GZMB-negative ENKTLs were often in a higher clinical stage (p = 0.016). We observed no other correlations with clinical parameters or TRG rearrangement and no significant association between GZMB expression and survival. In conclusion, GZMB expression is highly heterogeneous in ENKTLs and is associated with the activation of the JAK-STAT3 pathway and higher MYC expression. GZMB-negative ENKTLs correlate with an advanced clinical stage, suggesting the potential utility of GZMB immunohistochemistry as a biomarker of ENKTL.

NAA10 gene expression is associated with mesenchymal transition, dedifferentiation, and progression of clear cell renal cell carcinoma.

INTRODUCTION: We aimed to investigate the expression and prognostic role of NAA10 in clear cell renal cell carcinoma (ccRCC). MATERIAL AND METHODS: We performed a gene expression and survival analysis based on the human cancer genome atlas database of ccRCC patients (TCGA-KIRC). RESULTS: The patients in the TCGA-KIRC (n = 537) were divided into two subgroups: NAA10-low and NAA10-high expression groups. NAA10-high ccRCC exhibited higher T stages (p = 0.002), a higher frequency of distant metastasis (p = 0.018), more advanced AJCC stages (p < 0.001), a lower overall survival time (p = 0.036), and a lower survival rate (p < 0.001). NAA10-high ccRCC was associated with increased activity of non-specific oncogenic pathways, including oxidative phosphorylation (p < 0.001) and cell cycle progression [G2 to M phase transition (p = 0.045) and E2F targets (p < 0.001)]. Additionally, the NAA10-high tumors showed reduced apoptosis via TRIAL pathways (p < 0.001) and increased levels of activity that promoted epithelial-mesenchymal transition (p = 0.026) or undifferentiation (p = 0.01). In ccRCC, NAA10 expression was found to be a negative prognostic factor in both non-metastatic (p < 0.001) and metastatic tumors (p = 0.032). CONCLUSIONS: In ccRCC, NAA10 expression was shown to be a negative prognostic factor related to tumor progression rather than tumor initiation, and high NAA10 expression promoted epithelial-mesenchymal transition and undifferentiation.

Acquired Cystic Disease-Associated Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a common subtype of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients. The current systematic review and meta-analysis was performed to evaluate the clinicopathological, and genetic characteristics of patients with ACD-RCC. A systematic search on three electronic databases including the Pubmed, Scopus, and Web of Science databases were performed until December 31, 2022. A meta-analysis was performed following the PRISMA 2020 Guidelines. Of 888 identified articles, full-text screening in 69 articles, there were 26 articles analyzed, with a total of 2314 tumors in 2199 patients, including 418 ACD-RCC tumors in 363 patients, 1340 clear cell RCC (ccRCC) tumors, 308 papillary RCC (pRCC) tumors. Most ACD-RCC patients were male (80.2%). All the ACD-RCC patients underwent prior dialysis with 148.2 months of mean dialysis duration. There were 8.7%, 3.4%, and 5.8% tumors at the T3-4 stage, N1 stage, and M1 stage, respectively. The mean overall survival of ACD-RCC patients was 39.6 months (95% CI, 26.6-52.5). Compared to ccRCC and pRCC, ACD-RCC patients had a longer duration of dialysis (MD: 103.5 and 31.77 months, respectively; 95% CI: [75.48; 131.53] and [0.95; 62.58], respectively), and a higher rate of multifocal tumors (MD: 3.46 and 2.45 tumors, respectively; 95% CI [1.71; 6.98] and [1.26; 4.79], respectively). Regarding genetic characteristics, chromosomes 3 and 16 were the 2 most frequent chromosomal aberrations. The missense mutation in KMT2C (25%) and TSC2 (18.75%) were the 2 most common gene mutations in ACD-RCC. In conclusion, the ACD-RCC subtype exhibited several distinct clinicopathological and genetic characteristics compared to others RCC subtypes. Further researchs are needed to assess the survival outcome and the genetic characteristics of this subtype.

De novo Versus Secondary Dedifferentiated Chordomas: A Population-Based Analysis and Integrated Individual Participant Data Meta-Analysis.

OBJECTIVE: There is a lack of data about the clinicopathological and molecular characteristics of de novo versus secondary dedifferentiated chordoma (DC). This integrated study aimed to investigate the similarities and differences in clinicopathological manifestations, prognoses, and molecular profiles of these 2 subtypes. METHODS: We accessed the Surveillance, Epidemiology, and End Results (SEER) Program for DC cases from 1975 to 2020. Three electronic databases were also searched for additional DCs. Individual patient data of DC patients from SEER and published literature were combined in integrated analyses. RESULTS: After excluding duplicated patients, we identified 14 and 116 DC patients from SEER and published literature, respectively. There were 74 de novo, 39 secondary, and 18 cases with unknown origin. Our results showed that de novo and secondary DCs were not statistically different in terms of age, gender, primary location, tumor size, distant metastasis at diagnosis, extent of resection, and chemotherapy receipt. There was limited available molecular data for de novo and secondary DCs, though examples TP53 mutations were found in both. In addition, the rates of tumor relapse, metastasis during follow-up, and patient mortality were also comparable between the 2 groups. In the multivariate Cox regression model, we demonstrated that gross total removal and radiotherapy use were associated with prolonged survival of DCs. CONCLUSIONS: De novo and secondary DCs were statistically comparable in terms of patient demographics, clinical manifestations, and prognoses. Gross total excision and radiotherapy were optimal treatments associated with better outcomes of DC patients.

A Machine Learning-Based Model to Predict In-Hospital Mortality of Lung Cancer Patients: A Population-Based Study of 523,959 Cases.

Background: Stratify new lung cancer patients based on the risk of in-hospital mortality rate after diagnosis. Methods: 522,941 lung cancer cases with available data on the Surveillance, Epidemiology, and End Results (SEER) were analyzed for the predicted probability based on six fundamental variables including age, gender, tumor size, T, N, and AJCC stages. The patients were randomly assigned to the training (n = 115,145) and validation datasets (n = 13,017). The remaining cohort with missing values (n = 394,779) was then combined with the primary lung tumour datasets (n = 1018) from The Cancer Genome Atlas, Lung Adenocarcinoma and Lung Squamous Cell Carcinoma projects (TCGA-LUAD & TCGA-LUSC) for external validation and sensitivity analysis. Results: Receiver Operating Characteristic (ROC) analyses showed high discriminatory power in the training and internal validation cohorts (Area under the curve [AUC] of 0.78 (95%CI = 0.78-0.79) and 0.78 (95%CI = 0.77-0.79), respectively), whereas that of the model on external validation data was 0.759 (95%CI = 0.757-0.761). We developed a static nomogram, a web app, and a risk table based on a logistic regression model using algorithm-selected variables. Conclusions: Our model can stratify lung cancer patients into high- and low-risk of in-hospital mortality to assist clinical further planning.

NAA10 overexpression dictates distinct epigenetic, genetic, and clinicopathological characteristics in adult gliomas.

NAA10 is a novel biomarker of cancer progression. The oncogenic and biological mechanisms of NAA10 in human malignancies are controversial and remain to be elucidated. Herein, we investigated the biological and clinicopathological implications of NAA10 gene expression in adult gliomas. We collected data from The Human Cancer Genome Atlas (TCGA) database, including patients from TCGA-GBM and TCGA-LGG projects. In total, there were 666 patients from the 2 projects (513 and 153 from TCGA-LGG and TCGA-GBM, respectively). Different analyses (pathway, DNA methylation, and survival analyses) require further specific case eliminations. Based on NAA10 expression, we divided 666 tumors into 2 subgroups: NAA10-high and NAA10-low glioma. There were higher activities of cell proliferation, metabolic reprogramming, DNA repair, angiogenesis, epithelial-mesenchymal transition, TNF-α, IL6/JAK/STAT6, mTORC1 signaling, and MYC targets in NAA10-high glioma, while P53, TGF-ß, Wnt, and Hedgehog pathways were highly expressed by NAA10-low gliomas. t-distributed stochastic neighbors embedding dimension reduction of DNA methylation also showed a high distribution of NAA10-high gliomas in distinct clusters. Survival analyses showed that high NAA10 expression was an independent prognostic factor. NAA10 expression dictated epigenetic, genetic, and clinicopathological differences in adult glioma. Further studies are required to investigate the detailed NAA10 oncogenic mechanisms and to validate NAA10 immunohistochemistry.

Molecular and clinicopathological implications of PRAME expression in adult glioma.

BACKGROUND: PRAME (PReferentially expressed Antigen in MElanoma) is a biomarker studied in various human cancers. Little is known about the biological implications of PRAME in glioma. We aimed to perform a comprehensive analysis to explore PRAME gene expression and its biological and clinicopathological significance in gliomas. METHODS AND MATERIALS: We accessed the human cancer atlas (TCGA) database to collect glioma patients (n = 668) with primary tumors and gene expression data. Single nucleotide variants, copy number variation, DNA methylation data, and other clinicopathological factors were also extracted for the analysis. RESULTS: Overall, 170, 484, and 14 tumors showed no expression, low expression (FPKM≤1), and overexpression (FPKM>1) of the PRAME gene, respectively. The principal component analysis and pathway analyses showed that PRAME-positive gliomas (n = 498), which consisted of tumors with PRAME low expression and overexpression, expressed different oncogenic profiles, possessing higher activity of Hedgehog, P3IK-AKT-mTOR, and Wnt/ß-catenin pathways (p<0.001). DNA methylation analysis also illustrated that PRAME-positive tumors were distributed more densely within a grade 4-related cluster (p<0.001). PRAME positivity was an independent prognostic factor for poor outcomes in a multivariate cox analysis adjusted for clinical characteristics and genetic events. Kaplan-Meier analysis stratified by revised classification showed that PRAME positivity was solely associated with IDH-wildtype glioblastoma, grade 4. Finally, PRAME-overexpressing cases (n = 14) had the worst clinical outcome compared to the PRAME-negative and PRAME-low cohorts (adjusted p<0.001) in pairwise comparisons. CONCLUSION: PRAME expression statuses may dictate different biological and clinicopathological profiles in IDH-wildtype glioblastoma.

SLC22A3 that encodes organic cation transporter-3 is associated with prognosis and immunogenicity of human lung squamous cell carcinoma.

Background: SLC22A3, the gene which encodes organic cation transporter (OCT)-3, has been linked to the prognosis of several types of cancer. However, its role in lung squamous cell carcinoma (LSCC) has not been addressed elsewhere. Methods: We analyzed gene expression, DNA methylation, and clinicopathological data from The Cancer Genome Atlas - Lung Squamous Cell Carcinoma (TCGA-LUSC) (n=501), a publicly available database exclusively consisting of LSCC patients. Using a 5 FPKM (fragments per kilobase of exon per million mapped fragments) cut-off, we divided LSCC patients into two groups: patients with tumors possessing high and low SLC22A3 expression (SLC22A3-high and SLC22A3-low, respectively). Prognostic significance was determined through Cox analyses and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS). Differential methylation position (DMP), differentially gene expression, and pathway analyses were performed. Validation was carried out in GSE74777 (n=107), GSE37745 (n=66), GSE162520 (n=45) and GSE161537 (n=17). Results: SLC22A3-high LSCC patients had lower OS and DFS rates than SLC22A3-low LSCC patients. The different expression levels of SLC22A3 in LSCC were correlated with the methylation status of the SLC22A3 gene. Pathway analysis indicated that SLC22A3 expression levels were positively correlated with immune-related pathways such as inflammatory response and abundance of infiltrating immune cells in the tumor microenvironment (TME). Notably, in the SLC22A3-high group, many genes encoding immunological checkpoint inhibitory molecules were upregulated. In addition, SLC22A3 expression positively correlated with the Hot Oral Tumor (HOT) score, indicating high tumor immunogenicity. Conclusions: These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors.

Claudin-4 Upregulation in Acantholytic and Autoimmune-Mediated Bullous Disorders.

Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey-Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism.

A systematic review of the clinicopathological features and prognostic outcomes of DICER1-mutant malignant brain neoplasms.

OBJECTIVE: DICER1-mutant malignant brain neoplasms are very rare tumors, and published data have relied on case reports or small case series. In this review, the authors aimed to systematically summarize the types and distribution patterns of DICER1 mutations, clinicopathological characteristics, and prognostic outcomes of these tumors. METHODS: The authors searched PubMed and Web of Science for relevant studies. They included studies if they provided individual patient data of primary malignant brain tumors carrying DICER1 mutations. RESULTS: The authors found 16 studies consisting of 9 embryonal tumors with multilayered rosettes (ETMRs), 30 pineoblastomas, 52 primary intracranial sarcomas, and 27 pituitary blastomas. Pineoblastoma, ETMR, and pituitary blastoma were more likely to carry DICER1 germline mutations, while only a small subset of primary intracranial sarcomas harbored these mutations (p < 0.001). Nearly 80% of tumors with germline mutations also had another somatic mutation in DICER1. ETMR and primary intracranial sarcoma were associated with an increased risk for tumor progression and relapse compared with pituitary blastoma and pineoblastoma (p = 0.0025), but overall survival (OS) was not significantly different. Gross-total resection (GTR) and radiotherapy administration were associated with prolonged OS. CONCLUSIONS: ETMR, pineoblastoma, primary intracranial sarcoma, and pituitary blastoma should be considered rare phenotypes of the DICER1 syndrome, and families should be counseled and screened for associated tumors. ETMR and primary intracranial sarcoma had a higher risk of relapse. GTR and radiotherapy appeared to improve the OS of patients with DICER1-mutant malignant intracranial tumors.

Survival analyses of soft tissue pleomorphic sarcomas and a proposed leiomyosarcoma-specific dynamic nomogram: A large population-based study.

BACKGROUND: Pleomorphic sarcoma of soft tissue1 (PSST) is a heterogeneous group of sarcomas with different prognoses. Survival patterns of this tumor group have not been thoroughly investigated. Prognostic models should be developed to support individualized evaluation of PSST patients. MATERIALS AND METHODS: We collected cases of soft tissue tumors in the Surveillance, Epidemiology, and End Results2 (SEER) database, excluding tumors located in intra-abdominal and retroperitoneal regions. We included patients with histopathologic diagnoses of tumors in the PSST group (n = 14,685) and compared the survival patterns of the different histologic types. To develop a prognostic model of leiomyosarcoma, we divided leiomyosarcoma patients into two groups. The first group (n = 4136) was patients with missing values, which became our training cohort after imputation. The second group (n = 671) was the validation cohort. RESULTS: Leiomyosarcoma was the most common PSST (32.7 %). By pairwise comparison, we found that histologic types of PSST can be divided into 4 prognostic groups (p < 0.001). Regarding our model, the C-index, K statistic, and explained variation R2D were 0.84, 0.8, 0.52 (training cohort) and 0.76, 0.76, 0.4 (validation cohort), respectively. CONCLUSIONS: We found that the survival patterns of PSST can be divided into four distinct groups of histology types. Our dynamic nomogram can individualize the management of leiomyosarcoma patients and, therefore, can be very helpful for clinician-patient communication due to its applicability of flexibility.

Metastatic Risk Stratification of 2526 Medullary Thyroid Carcinoma Patients: A Study Based on Surveillance, Epidemiology, and End Results Database.

The risk of distant metastasis in medullary thyroid carcinoma (MTC) has not been well studied. Additional evaluation of MTC metastatic risk can be helpful for improving the quality of medical management. Therefore, we conducted a large population study to develop a method to stratify the risk of metastasis at the initial presentation of MTC patients. We collected 3612 MTC patients from the Surveillance, Epidemiology, and End Results (SEER) database, and included 2526 MTC patients in the study after applying exclusion criteria. We selected the most informative variables from a learning cohort of 2019 patients to obtain 1000 models by repetitive random data splicing into training and regularization cohorts. We selected the optimal model and developed a risk table from that model. Our risk table variables consist of age, gender, tumor size, extrathyroidal extension, and lymph node metastasis. The final model showed good calibration when metastatic risk was < 25% and good performance with areas under the curve (AUCs) of 0.81, 0.84, and 0.84 in the training, regularization, and test cohorts, respectively. We performed K-means clustering analysis on the model's metastatic estimation and determined three risk groups of patients with significant survival differences (p < 0.001). Low-risk patients had 0.88%, 1.3%, and 0.5% while high-risk patients had 19.7%, 15.8%, and 17.8% risk of metastasis in the three cohorts, respectively. The incorporation of our table into the International MTC Grading System (IMTCGS) requires more comprehensive clinicopathological studies.

Tumor-infiltrating lymphocytes in breast FNA biopsy cytology: A predictor of tumor-infiltrating lymphocytes in histologic evaluation.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are associated with various clinicopathological features. Using cytologic specimens for assessing TILs remains to be established. This retrospective study aimed to establish a practical method to assess TILs in cytologic samples. METHODS: The authors found 1101 breast fine-needle aspiration biopsy (FNAB) cytology samples in their hospital, and 214 of them met the inclusion criteria. The TILs score was evaluated using histologic slides, and breast cancers were divided into 2 groups: low- (<60%) and high-TILs (≥60%). Training and validation tests composed of 50 breast cancer samples each were constructed. A cytologic TILs (cTILs) score was introduced to evaluate lymphocytes in FNAB cytology and it was compared with histologically evaluated TILs. The cTILs score was calculated by subtracting the number of neutrophils from the number of lymphocytes surrounding the tumor cells. RESULTS: In the training test, a 2-tier system with low- and high-TILs groups showed a large area under the curve (AUC) (0.943; 95% confidence interval [CI], 0.84-0.99). A cTILs score cutoff value of >8 had 87.5% sensitivity and 90.5% specificity. In the validation test, the AUC was 0.79 (95% CI, 0.6-0.93) whereas sensitivity and specificity were 57% and 89.5%, respectively. When small tumors <0.5 cm were excluded, the AUC improved to 0.93 (95% CI, 0.83-1.0), and sensitivity and specificity were 80% and 88.5%, respectively. CONCLUSIONS: The cTILs scoring system had acceptable reproducibility and concordance with TILs on histologic samples for tumors ≥0.5 cm. Cytologic evaluation can potentially substitute for histologic evaluation of TILs.