Frequent Node Research Articles

Impact of the COVID-19 lockdown in France on the diagnosis and staging of breast cancers in a tertiary cancer centre

ObjectivesDue to COVID-19, a lockdown took place between March 17 and May 1, 2020, in France. This study evaluates the impact of the lockdown on the diagnosis and staging of breast cancers in a tertiary cancer centre.MethodsOur database was searched for all consecutive invasive breast cancers diagnosed in our institution during the lockdown (36 working days), during equivalent periods of 36 working days before and after lockdown and a reference period in 2019. The number and staging of breast cancers diagnosed during and after lockdown were compared to the pre-lockdown and reference periods. Tumour maximum diameters were compared using the Mann–Whitney test. Proportions of tumour size categories (T), ipsilateral axillary lymph node invasion (N) and presence of distant metastasis (M) were compared using Fisher’s exact test.ResultsCompared to the reference period (n = 40 in average), the number of breast cancers diagnosed during lockdown (n = 32) decreased by 20% but increased by 48% after the lockdown (n = 59). After the lockdown, comparatively to the reference period, breast cancers were more often symptomatic (86% vs 57%; p = 0.001) and demonstrated bigger tumour sizes (p = 0.0008), the rates of small tumours (T1) were reduced by 38%, locally advanced cancers (T3, T4) increased by 80% and lymph node invasion increased by 64%.ConclusionThe COVID-19 lockdown was associated with a 20% decrease in the number of diagnosed breast cancers. Because of delayed diagnosis, breast cancers detected after the lockdown had poorer prognosis with bigger tumour sizes and higher rates of node invasion.Key Points• The number of breast cancer diagnosed in a large tertiary cancer centre in France decreased by 20% during the first COVID-19 lockdown.• Because of delayed diagnosis, breast cancers demonstrated bigger tumour size and more frequent axillary lymph node invasion after the lockdown.• In case of a new lockdown, breast screening programme and follow-up examinations should not be suspended and patients with clinical symptoms should be encouraged to seek attention promptly.

812 PROGRAMMED CELL DEATH PROTEIN 1/PROGRAMMED DEATH LIGAND 1 AND HLA-CLASS I ARE POTENTIAL THERAPEUTIC TARGETS IN ESOPHAGEAL NEUROENDOCRINE CARCINOMA

Abstract Esophageal neuroendocrine carcinoma (NEC) is a rare and aggressive subtype with a poor prognosis. Pembrolizumab was recommended for the treatment of PD-L1 positive tumors in esophageal cancer and the combined positive score (CPS) was reported to be a better predictor of efficacy compared to the tumor proportion score (TPS). We investigated the expression profile of potential therapeutic targets (PD-L1, HLA class I, Mismatch repair (MMR) proteins) and tumor infiltrating lymphocytes (TILs) in esophageal NEC. Methods 15 NECs of the esophagus including mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma (SCC) component were investigated in the study. The expression of PD-L1 (quantitatively evaluated by CPS and TPS), HLA class I, and MMR protein expression were examined immunohistochemically. TIL abundance was examined semiquantitatively by observation of H&E slides. Results Nine (60%) showed a CPS ≥ 1, five (33%) showed a CPS ≥10, and five cases showed a TPS ≥1. Survival analysis showed a significantly longer overall survival in the CPS ≥1 group than in the CPS <1 group. Deficiency of MMR protein was not observed in any cases. HLA-Class I expression was retained in 10 (67%), and loss of HLA-Class I was significantly correlated with frequent lymph node metastasis, high TNM Stage, and low TIL. Three showed both PD-L1 CPS ≥ 10 and high TIL. Conclusion In esophageal NEC, PD-L1 positivity and preserved HLA-Class I expression were frequently observed, and PD-L1 CPS ≥ 1 was significantly associated with the better prognosis of esophageal NEC. Therefore, the PD-1/PD-L1 pathway and HLA-class I are thought to be potential therapeutic targets in esophageal neuroendocrine carcinoma.

AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1\u2013Bcl-6 axis-mediated B-cell differentiation

Absent in melanoma 2 (AIM2) has been reported to be a component of inflammasomes in innate immune cells. Surprisingly, AIM2 is expressed by B cells, and higher AIM2 expression is observed in the B cells from lupus patients. To date, the inflammasome-independent function of AIM2 in B cells remains unclear. Here, we report increased expression of AIM2 in human tonsil memory and germinal center (GC) B cells and in memory B cells and plasma cells from the circulation and skin lesions of lupus patients. Conditional knockout of AIM2 in B cells reduces the CD19+ B-cell frequency in lymph nodes and spleens, and dampens KLH-induced IgG1-antibody production. In a pristane-induced mouse model of lupus, AIM2 deficiency in B cells attenuates lupus symptoms and reduces the frequency of GC B cells, T follicular helper (Tfh) cells, plasmablast cells, and plasma cells. Furthermore, the loss of AIM2 in human B cells leads to the increased expression of Blimp-1 and reduces the expression of Bcl-6. However, the silencing of Blimp-1 and Bcl-6 has no significant effect on AIM2 expression, indicating that AIM2 might be the upstream regulator for Blimp-1 and Bcl-6. In addition, IL-10 is found to upregulate AIM2 expression via DNA demethylation. Together, our findings reveal that AIM2 is highly expressed in the B cells of lupus patients and promotes B-cell differentiation by modulating the Bcl-6–Blimp-1 axis, providing a novel target for SLE treatment.

Immunohistochemical and genetic characteristics of HPV-associated endocervical carcinoma with an invasive stratified mucin-producing carcinoma (ISMC) component.

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described entity of human papillomavirus (HPV)-associated endocervical adenocarcinoma with phenotypic plasticity and aggressive clinical behavior. To identify the cell of origin of ISMC, we investigated the immunohistochemical expression of cervical epithelial cell markers (CK7, PAX8, CK5/6, p63, and CK17), stemness markers (ALDH1 and Nanog), and epithelial-mesenchymal transition (EMT) markers (Snail, Twist, and E-cadherin) in 10 pure and mixed type ISMCs with at least 10% of ISMC component in the entire tumor, seven usual type endocervical adenocarcinomas (UEAs), and seven squamous cell carcinomas (SCCs). In addition, targeted sequencing was performed in 10 ISMCs. ISMC was significantly associated with larger tumor size (p = 0.011), more frequent lymphovascular invasion and lymph node metastasis (p < 0.001), higher FIGO stage (p = 0.022), and a tendency for worse clinical outcomes (p = 0.056) compared to other HPV-associated subtypes. ISMC showed negative or borderline positivity for PAX8, CK5/6, and p63, which were distinct from UEA and SCC (p < 0.01). Compared to UEA and SCC, ISMC showed higher expression for ALDH1 (p = 0.119 for UEA and p = 0.009 for SCC), Snail (p = 0.036), and Twist (p = 0.119), and tended to show decreased E-cadherin expression (p = 0.083). In next-generation sequencing analysis, ISMC exhibited frequent STK11, MET, FANCA, and PALB2 mutations compared to conventional cervical carcinomas, and genes related to EMT and stemness were frequently altered. EMT-prone and stemness characteristics and peripheral expression of reserve cell and EMT markers of ISMC suggest its cervical reserve cell origin. We recommend PAX8, CK5/6, and p63 as diagnostic triple biomarkers for ISMC. These findings highlight the distinct biological basis of ISMC.

Differences in the clinicopathological features of pancreatic head carcinoma in dorsal and ventral pancreas: A single institution retrospective review.

The embryonic development of the pancreas originates from dorsal and ventral anlagen, and the pancreatic cancer arising from dorsal or ventral pancreas may have different clinical pathology features. This study aims to explore whether there are differences in clinicopathological features and prognosis of pancreatic head carcinoma arising from dorsal or ventral pancreas.Between January 2014 and February 2018, 101 patients with resectable pancreatic head cancer who underwent pancreaticoduodenectomy in our institution were retrospectively reviewed. The patients were assigned into 2 groups according to tumor location on preoperative imaging materials (computed tomography/magnetic resonance imaging [CT/MRI]), and the clinicopathological features and prognosis were retrospectively analyzed in view of the embryonic development of the pancreas.Among these patients with pancreatic head cancer, 42 patients had tumors arising from dorsal pancreas (D group) and 59 patients had tumors arising from ventral pancreas (V group). The frequency of lymph node (LN) metastasis around the common hepatic artery (CHA) and hepatoduodenal ligament lymph nodes in the D group was higher than that in the V group (45.2% vs 10.2%, P = .001). And the rate of LN metastasis in the superior mesenteric artery (SMA) region in the V group is higher than that in the D group (32.2% vs 4.8%, P = .002). The D group was more likely to invade the common bile duct (78.6% vs 59.3%, P = .042) and duodenum (71.4% vs 44.1%, P = .006) than the V group. In addition, the survival outcome of V group was better than D group (median overall survival [OS], 15.37 months vs 10.53 months, P = .048, median DFS 9.73 months vs 5.93 months, P = .046).The clinicopathological features of pancreatic head carcinoma arising from dorsal or ventral pancreas are different, and the pancreatic head carcinoma arising from ventral pancreas has a better survival outcome.

Molecular classification of breast cancer

Background: Breast cancer is a heterogeneous disease with different biological and histological properties due to genetics and epigenetic changes with varying clinical features and treatment responses. This study was planned and carried out with the objective to classify breast cancers molecularly using surrogate markers, ER, PgR, Her2/neu and Ki67 and correlate the various types with conventional prognostic markers. Materials and Methods: 70 cases of invasive breast carcinomas were subjected to routine staining and immunohistochemistry with estrogen receptors(ER), progesterone receptors (PgR), Her2/neu and Ki67and classified into molecular subtypes as defined in various studies. These were correlated with other conventional prognostic parameters and analyzed statistically. Result: 70 cases of invasive breast cancer were classified into 18(22%) cases of luminal B, 16(25%) cases of Her2/neu and triple negative each and 14(22%) cases of luminal A subtypes. There was an even distribution of molecular subtypes varying from 22 to 28%. Luminal B and Her subtype were commoner in the Indian setting as compare to other studies. Luminal A and Luminal B subtypes were commoner in patients older than 50 years. Her2/neu and TNBC cases were more commonly of higher histological grade and pathological stage, while Luminal A and B subtypes showed lower grade and stages. Luminal B subtype and Her2/neu subtypes showed DCIS more often and Luminal B and TNBC subtypes, more frequent lymph node metastasis. Conclusion: The molecular classification of breast cancer by IHC in this study population showed an almost equal distribution of the 4 subtypes. The association of tumor grade and LVI with the molecular subtypes showed a significant correlation. Keywords: ER, PR, Her2/neu, Ki67.

Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients

Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis.

Reliability Analysis of Gasifier Lock Bucket Valve System Based on DBN Method

In order to solve the problem of zero-failure data and dynamic failure in gasification system, a dynamic Bayesian network (DBN) combined with Monte Carlo simulations is proposed to analyze the reliability of the gasifier lock bucket valve system. On the basis of studying the structure of the gasifier lock bucket valve system, the reliability model of the system is built based on DBN, and the structure learning is realized. The Monte Carlo simulation is used for the timed ending test in Bayesian estimation, which effectively solves the problem of zero-failure data and realizes the parameter learning. Through the Metropolis-Hastings (M-Hs) algorithm, the prior distribution of dynamic node is randomly sampled to obtain the target distribution, which makes the reliability predictive inference for DBN of the gasifier lock bucket valve system faster and more accurate. The obtained reliability prediction is a curve varying with time. The results show that the valve frequent switch node of DBN of the gasifier lock bucket valve system is identified as the weak link by the powerful reverse inference for DBN, which needs to be paid more attention to. This method can effectively improve the maintenance level of the gasifier lock bucket valve system and can effectively reduce the possibility of accidents.

Real-life use of BRAF-V600E mutation analysis in thyroid nodule fine needle aspiration: consequences on clinical decision-making.

This study aimed to evaluate the real-life use of BRAF-V600E mutation analysis in washout liquid from thyroid nodule fine needle aspiration (FNA), and the consequences of genetic result on clinical decision-making. We retrospectively considered subjects tested for BRAF-V600E among those attending the Endocrinology Unit of Modena for FNA between 2014 and 2018. Washing fluid was collected together with cytological sample and stored at -20 °C. If the clinician deemed it necessary, the sample was thawed, DNA extracted, and genetic test performed by high-resolution melting technique. We collected data on cytology according to the Italian Consensus for the cytological classification of thyroid nodules, type of surgery (when performed), histology, and adverse events. Out of 7112 subjects submitted to FNA, BRAF analysis was requested for 683 (9.6%). Overall, 896 nodules were analyzed: 74% were indeterminate at cytology, mainly TIR3A (low risk). Twenty-two nodules were mutant (BRAF+). Only 2% of indeterminate, mainly TIR3B, were BRAF+. Based on final histological diagnosis, BRAF test had high specificity (100%) but poor sensitivity (21%), also in indeterminate nodules. Mutant subjects underwent more extensive surgery compared to wild type (p = 0.000), with frequent prophylactic central lymph node dissection. One third had local metastases. Higher prevalence of hypoparathyroidism was found in BRAF+ compared to wild type (p = 0.018). The analysis of BRAF-V600E outside of gene panels has low sensitivity, especially in indeterminate nodules, and a positive result could lead to more extensive surgery with greater risk of hypoparathyroidism and questionable clinical utility.

Significance of serum CA125 level in surgically resected cervical adenocarcinoma with adverse features.

ObjectiveUnlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features.MethodsA total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model.ResultsUsing a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7–97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003).ConclusionIn this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of ≥50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors.

Značajke snimki trostruko negativnih karcinoma dojke

Breast cancer (BC) is a highly heterogeneous disease. Aim was to evaluate imaging features of triple negative breast cancers (TNBC) in comparison to non-TNBC. We reviewed data of 30 patients who had been diagnosed as having TNBC and 37 patients with non-TNBC (control group) using criteria described for mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) in Breast Imaging-Reporting and Data System (BI-RADS) lexicon for image interpretation. Age of patients, size of tumor, multifocality, histological type, tumor grade and status of lymph nodes were reviewed. TNBC were more often histological grade 3 and had significantly more positive lymph nodes at the time of diagnosis on pathology reports. On MMG, US and MRI TNBC mostly appeared as regularly shaped masses. On US as hypoechogenic masses with no posterior acoustic features and on MRI as masses with rim type of enhancement, fast wash-in and plateau type of curves. Most frequent category reported after MMG and US was BI RADS 4, and after MRI BI RADS 5. In conclusion, our study confirmed higher histological grade of TNBC, as well as more frequent lymph node involvement in comparation to the non-TNBC. TNBC showed tendency to affect younger women and to be larger than non-TNBC. Although, they most often presented as a mass on mammography and sonography, in a significant number of cases they remained miscategorized, due to the benign imaging features. All cases are recognized on MRI where they appear as rim enhancing masses.

How to write medical abstracts? The rhetorical structure and phrases used in Epidemiology

Introduction: Abstracts are critical in medical contexts. They contain formulaic building blocks called Lexical Frames (LFs), which are high-frequency word sequences with variable slots that can be formed around collocation nodes. LFs are abundant in written academic discourse, and , for this reason, have great importance for the production of abstracts. Extensive research has been conducted on formulaic language, especially on medical genres. Fewer studies, however, have focused on LFs from specialty-specific corpora (.e.g., epidemiology) and their relationship with the rhetorical structure of abstracts. Objective: This study aims to fill this gap by describing the structure of epidemiology abstracts, presenting their rhetorical functions, and identifying the LFs that linguistically realize these functions to help researchers write more conventional abstracts. Methods: We put together three corpora of abstracts in the field, published in English in peer-reviewed journals, and combined genre analysis and Corpus Linguistics principles to identify the linguistic realizations of the rhetorical functions in the texts. First, the rhetorical structure was described; then, the LFs were identified and analyzed. Results: 92% of the texts follow a pre-established pattern, whose structure consists of five to nine sections. Eight saliently frequent nodes (study, result, method, conclusion, review, analysis, patients, and findings) around which the LFs are constructed were identified. Conclusion: Even though both the content and function words that make up the LFs show some variation, it is possible to notice that the LFs elicited typify the linguistic realizations of the corresponding sections' rhetorical functions and, thus, are suitable to the observation of a pattern. For that reason, the data obtained in this study were used to inform the creation of a support framework for the writing of specialty-specific medical abstracts.

Resilient Range-Based d-Dimensional Localization for Mobile Sensor Networks

Knowledge of node locations is essential to Wireless Sensor Networks (WSNs) in a wide range of potential applications and their function-dependent network protocols. A number of localization approaches have already been proposed to fulfill this requirement, but few of them can be applicable to mobile sensor networks, due to their low-dimensional embeddings, Euclidean distance representation limitations, frequent node mobility and additional measurement overhead in the network. In this paper, a resilient range-based $d$ -dimensional localization (RRDL) approach is proposed for mobile WSNs to resolve the issues. RRDL distinguishes itself from previous work with three remarkable characteristics: (1) it works for mobile networks embedded in $d$ -dimensional Non-Euclidean space; (2) it allows static ordinary nodes with pre-known locations to act as the alternative anchor nodes, thus tolerating the motion of the original anchor nodes to ensure that other ordinary nodes can obtain their locations in an efficient manner; and (3) it introduces an efficient path-learning approach, with the knowledge of the existing paths, to represent the real network distances as far as possible, thereby eliminating additional measurement overhead and tolerating node mobility in localization. With these characteristics, RRDL exploits the iterative factorization of the random distance matrix, formed by the distances to and from a set of $k$ -hop static neighbors, to assign each current node $d$ -dimensional Non-Euclidean coordinate in a distributed manner. Simulation results demonstrate that RRDL achieves higher localization accuracy with a moderate communication cost in mobile sensor networks.

Outcomes of extensive surgeries in combination treatment of stage III–IV ovarian cancer

Objective: to evaluate short-term and long-term outcomes of lymph node dissection in patients with stage III–IV ovarian cancer.Materials and methods. This retrospective study included patients with stage III–IV ovarian cancer who have undergone either complete or optimal cytoreduction. Patients in the experimental group additionally had lymph node dissection, whereas patients in the control group had surgery without lymph node dissection. We evaluated 3‑year relapse-free survival (primary outcome measure), 3‑year overall survival, incidence of intraoperative and postoperative complications, and frequency of lymph node lesions.Results. The study included 272 patients: 43 women in the experimental group and 229 women in the control group. Intraoperative complications were significantly more common in patients who had lymph node dissection compared to those who had cytoreductive surgery alone (37.2 % vs 16.6 % respectively; р = 0.0001). The incidence of postoperative complications did not vary significantly between the groups (27.9 % in the experimental group vs 16.2 % in the control group; р = 0.128). Thirty-three patients (76.7 %) were found to have metastasis in the lymph nodes excised. The three-year overall survival rate was 82.6 % among patients who had lymph node dissection and 75.7 % among patients who had no lymph node dissection (р = 0.306). The three-year relapse-free survival rate was 26.2 % in the experimental group and 38.4 % in the control group (р = 0.858).Conclusions. Systemic lymph node dissection does not improve long-term outcomes and increases the incidence of intraoperative complications in patients with stage III–IV ovarian cancer undergoing complete or optimal cytoreduction.

Cetuximab and paclitaxel combination therapy for recurrent basaloid squamous cell carcinoma in the ethmoid sinus

Basaloid squamous cell carcinoma (BSCC), a histologically distinctive variant of squamous cell carcinoma comprising basal cell carcinoma and squamous cell carcinoma, is aggressive and shows a poor prognosis because of frequent lymph node invasion and distant metastases. To date few articles regarding chemotherapy for metastatic disease have been reported, thus feasible chemotherapy is not well established. Cetuximab is a monoclonal antibody for epithelial growth factor receptor (EGFR), which has great efficacy for head and neck squamous cell carcinoma due to EGFR signaling pathway blockage. Because BSCC also highly expresses EGFR, cetuximab may be effective for BSCC. We report here a first case of recurrent BSCC in the ethmoid sinus with intracranial extension treated with cetuximab-based chemotherapy, which revealed great response in a 40-year-old man. Positron emission tomography (PET) revealed no lymph node or distant metastasis. The patient underwent chemoradiotherapy 66 Gy in 33 fractions with triweekly 100 mg/m2 cisplatin. However, 12 weeks after treatment completion PET revealed a residual tumor at the primary cancer site. Combination therapy with weekly paclitaxel and cetuximab was started, and complete response was observed 2 months from treatment initiation. The patient has maintained complete response for 32 months, and no tumor regrowth has been observed.

RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas.

Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.

Long Noncoding RNA ST7-AS1 Upregulates TRPM7 Expression by Sponging microRNA-543 to Promote Cervical Cancer Progression.

PurposeST7 antisense RNA 1 (ST7-AS1) is a long noncoding RNA that affects the progression of gastric cancer and laryngeal squamous cell carcinoma. Herein, ST7-AS1 expression was detected in cervical cancer tissues and cell lines. In addition, its biological roles in inducing the aggressive phenotype of cervical cancer and its associated mechanisms of action were illustrated.Patients and MethodsST7-AS1 expression in cervical cancer tissues and cell lines was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Malignancy was determined using Cell Counting Kit-8 assay, flow cytometry, transwell migration and invasion assays, and xenograft experiments. Bioinformatics analysis was performed to predict the interaction between ST7-AS1 and microRNA-543 (miR-543). Luciferase reporter assay, RNA immunoprecipitation assay, Western blotting, qRT-PCR, and rescue experiments were performed to further identify the interactions among ST7-AS1, miR-543, and transient receptor potential melastatin 7 (TRPM7).ResultsST7-AS1 was upregulated in cervical cancer tissues and cell lines. ST7-AS1 overexpression was correlated with a high International Federation of Gynecology and Obstetrics stage, frequent lymph node metastasis, deep cervical invasion, and short overall survival in patients with cervical cancer. ST7-AS1 inhibition hindered cervical cancer cell proliferation, migration, and invasion; ST7-AS1 downregulation resulted in marked cell apoptosis. Additionally, ST7-AS1 deficiency restricted cervical tumor growth in vivo. Mechanistically, ST7-AS1 functioned as competing endogenous RNA to increase TRPM7 expression by sponging miR-543. Intriguingly, rescue experiments revealed that miR-543 downregulation or TRPM7 overexpression abrogated the inhibitory actions of ST7-AS1 knockdown in the aggressive phenotype of cervical cancer cells.ConclusionThe newly identified ST7-AS1/miR-543/TRPM7 axis promoted the oncogenicity of cervical cancer cells both in vitro and in vivo. Our study highlighted the importance of this novel axis in cervical cancer progression, suggesting that this pathway can serve as a promising therapeutic target for cervical cancer.

Immunophenotypic and pathologic heterogeneity of unclassified renal cell carcinoma: a study of 300 cases

Renal cell carcinoma, unclassified (RCC-U), is a heterogenous group of tumors that do not fit in any of the recognized histologic types. Immunohistochemical studies are frequently used to characterize these tumors. Herein, we sought to investigate the immunophenotypes of 300 cases of RCC-U. The cases were morphologically classified into three groups: oncocytoma/chromophobe renal cell carcinoma-like, group 1; clear cell renal cell carcinoma-like, group 2; and others (ie, papillary renal cell carcinoma-like/collecting duct-like/pure sarcomatoid), group 3. The male-to-female ratio was 1.4. Most cases (168, 66%) were group 1. Group 3 was associated with larger tumor size, advanced stage, and frequent lymph node metastases. The most commonly used immunohistochemical stains were CK7 (n=270; 89.5%), vimentin (n=186, 82%), CD10 (n=181; 59.9%), and AMACR (n=162; 54%). Pancytokeratin (79/101; 78.2%) and PAX8 (54/61; 88.5%) were diffusely positive in most cases, followed by AMACR (69/117; 59%). CD117 was positive in 53 of 118 cases (45%). RCC-U is a morphologically and immunophenotypically heterogenous group of tumors, and comprehensive workup is needed before rendering the diagnosis.

Interleukin-22 promotes the migration and invasion of oral squamous cell carcinoma cells

The roles of interleukin-22 (IL-22) in carcinogenesis have been proposed in various neoplasms. Increased expression of IL-22 has been observed in oral squamous cell carcinoma (OSCC) lesions as well as in other cancers. OSCC is still associated with poor prognosis and a high mortality rate because of its invasiveness and frequent lymph node metastasis. In the present study, we investigated the effects of IL-22 on OSCC cells. The human OSCC cell lines Ca9-22 and SAS were stimulated with IL-22 (1–10 ng/mL), and their migration abilities were examined using a cell scratch assay. A Matrigel invasion assay was performed to evaluate the invasion abilities of OSCC cells. Signal transducer and activator of transcription 3 (STAT3) phosphorylation, matrix metalloproteinase (MMP) and epithelial-mesenchymal transition (EMT)-related genes and proteins were also examined. IL-22 treatment promoted the migration and invasion abilities of OSCC cells without increasing their viability. IL-22 stimulation also induced STAT3 phosphorylation, MMP-9 activity and EMT-related genes and proteins. Our findings suggest that IL-22 has possible roles in the development of OSCC.

Signet Ring Cell Gastric Carcinoma: Clinical Epidemiology and Outcomes in a Predominantly Latino County Hospital Population.

Gastric signet ring cell carcinoma (GSRC) is a rare but increasingly prevalent tumor histotype whose clinical features and natural history are poorly understood, particularly in the USA and minorities. To examine the occurrence, clinico-demographic characteristics, oncologic features, treatment, and outcomes of GSRC in a predominantly minority county hospital setting and benchmark them against data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. We queried biopsy-proven GSRC cases at a Los Angeles County hospital, from 2004 to 2017. Clinical characteristics, treatment, and survival data were collected and compared to SEER data. We identified 63 patients with GSRC. Compared to SEER, our cohort was significantly younger (52.6 vs. 63.5years, p < 0.01), Hispanic/Latino predominant (81% vs. 20%, p < 0.01), had higher overall stage (86% vs. 69% with stage III/IV, p < 0.01), and more frequent node involvement (89% vs. 49%, p < 0.01). Lower tumor stage, Helicobacter pylori positivity, and surgical intervention were associated with significantly longer median survival (all p < 0.05), which was similar in our study compared to SEER (median 12.6 vs. 9.0months, p = 0.26). Patients with GSRC within the Los Angeles County population have different clinical characteristics compared to what has been reported in SEER. Our cohort was younger, and despite having more advanced disease, did not have shorter survival. Further study is needed to better identify protective and risk factors in this population and improve understanding of the etiopathogenesis and natural history of this malignancy.