scholarly journals Quantification of Tumour Vascularity in Squamous Cell Carcinoma of the Tongue Using CARD Amplification, a Systematic Sampling Technique, and True Colour Image Analysis

2001 ◽  
Vol 22 (4) ◽  
pp. 183-192 ◽  
Author(s):  
Egied J. M. Hannen ◽  
Jeroen A. W. M. van der Laak ◽  
Harold M. J. Kerstens ◽  
Vincent M. J. I. Cuijpers ◽  
Antonius G. J. M. Hanselaar ◽  
...  

The aims of this study of head and neck tissue samples were to develop an immunohistochemical protocol based on the catalysed reporter deposition (CARD) technique to enhance staining results for use in automated true colour image analysis, to assess the reproducibility of systematic tissue sampling in the angiogenic hot spot selection, and quantification of microvessel density (MVD) and other vessel characteristics. The latter data were compared between six metastasised tongue squamous cell carcinomas, vs. four non-metastasised. In comparison to the standard immunohistochemical protocol with anti-CD34 antibodies, CARD amplification resulted in both more intensely stained and larger numbers of vessels. Averaging the 10 most vascularised fields of the 40 to 60 systematically sampled fields in a tissue section resulted in an overall acceptable interobserver reproducibility for most assessed vessel parameters (r≧ 0.76 andp≦ 0.01). The percentage vessels with diameter <5 μm was significantly higher in the non-metastasised tongue carcinomas (p= 0.02). However, for a number of tumours the effect of tissue sampling was significant. We conclude that CARD amplification is needed for reliable segmentation of vessels by image analysis systems, and that tumour heterogeneity is a limiting factor for all procedures in which tumour vascularity is assessed in a single tissue section.

2003 ◽  
Vol 23 (1) ◽  
pp. 124-127
Author(s):  
Isabel Sebastáan ◽  
V Santé ◽  
G Le Pottier ◽  
Pascale Marty-Mahé ◽  
P Loisel ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qi-Fan Yang ◽  
Di Wu ◽  
Jian Wang ◽  
Li Ba ◽  
Chen Tian ◽  
...  

AbstractLung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.


2021 ◽  
Vol 147 (4) ◽  
pp. 1125-1135
Author(s):  
Sang Kyum Kim ◽  
Jang-Hee Kim ◽  
Jae Ho Han ◽  
Nam Hoon Cho ◽  
Se Joong Kim ◽  
...  

Abstract Purpose Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. Methods In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. Results Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. Conclusion Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.


2007 ◽  
Vol 20 (2) ◽  
pp. 73-79 ◽  
Author(s):  
Lars Helge Stien ◽  
Anders Kiessling ◽  
Fredrik Manne

Author(s):  
Dany Gatsinzi ◽  
Francisco J Saez Nieto ◽  
Irfan Madani

This paper discusses a possibility to evolve the current Air Traffic Flow and Capacity Management towards a more proactive approach. This new method focuses on reducing the expected probability of air traffic control intervention based on “hot spot” identification and mitigation at strategic level by applying subliminal changes on the times of arrival at the crossing or merging points (junctions). The concept is fully aligned with the trajectory-based operation principles. The approach assumes that the changes on the times of arrival only demand small speed changes from the involved aircraft. In this study, the hot spots are defined as clusters of aircraft expected to arrive to the junctions. Two aircraft are said to be in the same cluster if their proximity and closure rate are below a given threshold. Some exercises are proposed and solved by applying this method. The obtained results show its ability to remove the potential conflicts by applying simple linear programming. This approach seeks to change the current capacity limiting factor, established by the number of aircraft occupying simultaneously each sector, to another parameter where the level of traffic complexity, flowing towards junctions, is identified and mitigated at strategic level. The speed changes, used as the control variable and computed before or during the flight, are designed to provide an adjustment on aircraft’s required time of arrival at the junctions in order to have a de-randomised and well-behaved (conflict free) traffic. This will enable improvements in airspace capacity/ safety binomial. It is recognised that this measure alone is unable to produce a conflict free airspace, and then other collaborative and coordinated actions, such as adjusting and swapping departing times at the departing airports (before the aircraft are taking off), offsetting some flights from nominal route, and allowing multi-agent separation management (while they are in flight) should be applied together with this method.


2019 ◽  
Author(s):  
Giorgio Cattoretti ◽  
Francesca Maria Bosisio ◽  
Lukas Marcelis ◽  
Maddalena Maria Bolognesi

Abstract Multiplexing, labeling for multiple immunostains the very same cell or tissue section in situ, is of considerable interest. The major obstacles to the diffusion of this technique are high costs in custom antibodies and instruments, low throughput, scarcity of specialized skills or facilities. We have validated and detail here a method based on common primary and secondary antibodies, diffusely available fluorescent image scanners and routinely processed tissue sections \(FFPE). It entails rounds of four-color indirect immunofluorescence, image acquisition and removal \(stripping) of the antibodies, before another stain is applied. The images are digitally registered and the autofluorescence is subtracted. Removal of antibodies is accomplished by disulphide cleavage. In excess of 50 different antibody stains can be applied to one single section from routinely fixed and embedded tissue. This method requires a modest investment in hardware and materials and uses freeware image analysis software.


2020 ◽  
Author(s):  
Tianyu Cui ◽  
Menghua Li ◽  
Cheng Lu ◽  
Min Xia ◽  
Zhaoyang Ke ◽  
...  

Abstract Background Motivation: Laryngeal squamous cell carcinoma (LSCC) is one of the relatively common malignant tumors occurring in the epithelial tissue of the larynx. Recently study showed that tumor immunity mechanisms have highly correlation with the development and progression of LSCC. With the development of research on circular RNA (circRNA) in recent years, a large number of abnormal expressions of circRNA in various tumors have been reported. There is a large number of evidences indicated that circRNA is widely involved in stage development of tumors and it also plays an important role as a biomarker in diagnosis and treatment. Therefore, the study of the pathways involved in the development of tumor by circRNA is a necessary process for humans to further understand cancer at the transcriptional level. The purpose of this study was to identify the circRNAs in tumor tissues of patients with laryngeal squamous cell carcinoma (LSCC) by NGS technique and to find the circRNAs that were significantly different from normal adjacent tissues. Finally, the mechanism of these differentially expressed tumor immunity circRNAs affecting LSCC development was further analyzed. Methods Raw data was mapped to Hg19 human genome and circRNA read count matrix was generated by featureCount software. In this study, the screening criteria for differential expression were p-value < 0.01 and | log2(FoldChange) | > 2.0. Filtered circRNAs were then applied for generating circRNA-miRNA-mRNA interaction network with known human micro RNA (miRNAs). After filtering unmeaning interactions, network-involved mRNAs were implement to KEGG analysis. Among those KEGG terms, immunity-related pathways were selected and their related circRNAs were chosen for further analysis. Second KEGG analysis then performed to these circRNAs for detecting their potential to be biomarkers. Finally a QRT-PCR experiment was used to verify the results. Results Among the 8 samples, 4 were LSCC tumor tissue samples and 4 were adjacent normal tissue samples. A total of 75,931 circRNAs were identified in total 8 samples. After filtering through the above screening criteria, we obtained 39 significantly differential expressed circRNAs from those identified candidates. Of the 39 circRNAs, 21 were detected to be significantly less expressed in LSCC tissues than in adjacent normal tissues, and other 18 were significantly higher. Through the interaction analysis of circRNA-miRNA-mRNA, we found that these differential expressed circRNAs were related to tumor immunity. After screening, four circRNAs with the strongest correlation with tumor immunity were obtained. We found that they play an important role in the membrane receptor tyrosine protein kinase signaling pathway pathway (Ras-Raf-MAPK pathway) and p53 signaling pathway. Conclusion According to the results, the method of detecting expression of four selected circRNAs has a bright future to be a kind of new LSCC diagnose approach.


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