scholarly journals Post-neoadjuvant cellular dissociation grading based on tumour budding and cell nest size is associated with therapy response and survival in oesophageal squamous cell carcinoma

2019 ◽  
Vol 121 (12) ◽  
pp. 1050-1057 ◽  
Author(s):  
Moritz Jesinghaus ◽  
Melanie Boxberg ◽  
Dirk Wilhelm ◽  
Stefan Münch ◽  
Hendrik Dapper ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
Therapy Response ◽  
Nest Size ◽  
Tumour Regression ◽  
Prognostic Impact ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Tumour Budding

Abstract Background Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant therapy. Methods We evaluated cell nest size and tumour budding activity in 122 post-neoadjuvant ESCC resections, correlated the results with tumour regression groups and patient survival and compared the results with data from primary resected cases as well as pre-therapeutic biopsies. Results CDG remained stable when results from pre-therapeutic biopsies and post-therapeutic resections from the same patient were compared. CDG was associated with therapy response and a strong predictor of overall, disease-specific (DSS) and disease-free (DFS) survival in univariate analysis and—besides metastasis—remained the only significant survival predictor for DSS and DFS in multivariate analysis. Multivariate DFS hazard ratios reached 3.3 for CDG-G2 and 4.9 for CDG-G3 neoplasms compared with CDG-G1 carcinomas (p = 0.016). Conclusions CDG is the only morphology-based grading algorithm published to date, which in concert with regression grading, is able to contribute relevant prognostic information in the post-neoadjuvant setting of ESCC.

Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance

2018 ◽  
Vol 72 (4) ◽  
pp. 285-294 ◽  
Author(s):  
Melanie Boxberg ◽  
Christine Bollwein ◽  
Korinna Jöhrens ◽  
Peer-Hendrik Kuhn ◽  
Bernhard Haller ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Interobserver Reliability ◽  
Training Session ◽  
Nest Size ◽  
Grading System ◽  
Tumour Entity ◽  
Aggressive Clinical Course ◽  
Tumour Budding

AimsSquamous cell carcinoma of the oral cavity (OSCC) is a common tumour entity with a variable, partially highly aggressive clinical course. Recently, we proposed a novel (three-tiered) clinically useful grading scheme strongly associated with patient outcome in OSCC, consisting of a sum score of the histomorphological patterns tumour budding and cell nest size which outperforms WHO based grading algorithms currently in use. The aim of our study was to probe for interobserver and intraobserver reliability of this novel grading system.Methods108 OSCC were retrospectively scored according to the proposed grading scheme by three independent pathologists—two experienced head and neck pathologists and one pathologist in training—blinded to each other’s scoring results.ResultsThe Cohen’s Kappa (κ) values for concordance rates between experienced pathologists were κ=0.97 for the overall grade, κ=0.97 for budding activity and κ=0.91 for cell nest size, indicating a strong interobserver reliability of our proposed grading system. Initial interobserver agreement was markedly lower with the pathologist in training (κ=0.55 for overall grade) but improved significantly after a training session (κ=0.87 for overall grade). Intraobserver concordance was high (κ=0.95 for overall grade), indicating a high reproducibility of the algorithm.ConclusionsIn conclusion, our study indicates that OSCC grading based on our proposed novel scheme yields an excellent inter-reader and intrareader agreement, further supporting the suitability of this grading system for routine pathological practice.

The prognostic impact of neutrophil to lymphocyte ratio in patients with recurrent or metastatic esophageal squamous cell carcinoma receiving immune checkpoint inhibitors.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 69-69
Author(s):  
Jhe-Cyuan Guo ◽  
Chia-Chi Lin ◽  
Ta-Chen Huang ◽  
Min-Shu Hsieh ◽  
Chih-Hung Hsu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
White Blood Cells ◽  
Neutrophil To Lymphocyte Ratio ◽  
Prognostic Impact ◽  
Response Evaluation ◽  
Lymphocyte Ratio

69 Background: The study explored the prognostic impacts of clinical parameters including neutrophil to lymphocyte ratio (NLR) in recurrent/metastatic esophageal squamous cell carcinoma (R/M ESCC) patients receiving anti-programmed cell death protein-1 (PD-1)/PD ligand 1 (PD-L1)-based therapy. Methods: Thirty-eight patients were enrolled. Tumor response evaluation was made according to Response Evaluation Criteria in Solid Tumours 1.1, and the clinical benefit response (CBR) was defined as complete response, partial response or stable disease at least 6 months. Clinical factors were analyzed for their impacts on patients' overall survival (OS) and progression-free survival (PFS). Formalin-fixed, paraffin-embedded tissues from 8 patients were analyzed by NanoString nCounter Human PanCancer Immune Profiling (NanoString Technologies, Seattle, WA, US). Results: Twenty-six recurrent and 12 de novo metastatic ESCC patients were enrolled. The response rate is 11.8%, and the CBR rate was 21.1%. The median PFS and OS are 2.7 and 5.5 months, respectively. The CBR group has lower blood white blood cells (WBC) ( P = 0.029), monocytes (p = 0.003), and NLR (p = 0.005). In univariate analysis, WBC, neutrophils, and NLR were statistically associated with PFS; performance status (PS), disease extent, albumin, WBC, neutrophils, and NLR were statistically associated with OS. In multivariate analysis, NLR (p = 0.007) was statistically associated with PFS; PS (p = 0.029) and NLR (p = 0.050) were statistically associated with OS. On examining the immune-related genes in ESCC tissues’ microenvironment, the ratios of mast cells, neutrophils, and macrophages relative to tumor-infiltrating lymphocytes (TILs) have significantly lower in the CBR group than in the non-CBR group. Conclusions: High NLR was associated with inferior prognosis in R/M ESCC patients receiving anti-PD-1/PD-L1-based therapy. The increased ratio of neutrophil to TILs in the ESCC tumor microenvironment of non-CBR patients may suggest a mechanistic role of neutrophils in affecting the efficacy of anti-PD-1/PD-L1 therapy. (Supported by the grant of MOST 105-2314-B-002 -186 -MY3)

Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system

2017 ◽  
Vol 70 (7) ◽  
pp. 1125-1137 ◽  
Author(s):  
Melanie Boxberg ◽  
Moritz Jesinghaus ◽  
Christiane Dorfner ◽  
Carolin Mogler ◽  
Enken Drecoll ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Nest Size ◽  
Grading System ◽  
Tumour Budding

scholarly journals Clinical application value of the prognostic nutritional index for predicting survival in patients with oesophageal squamous cell carcinoma undergoing chemoradiotherapy or radiotherapy

2020 ◽  
Author(s):  
Ling Xiao ◽  
Jiahua Lyu ◽  
Xiao Liu ◽  
Ke Li ◽  
Yuan Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Application ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Entire Group ◽  
Oesophageal Squamous Cell Carcinoma ◽  
T Stage ◽  
Tumour Length

Abstract Background : The prognostic nutrition index (PNI) has been shown to have prognostic value for several common cancers. The study aim was to explore the clinical application value of the PNI for prognosis of patients with oesophageal squamous cell carcinoma (ESCC) treated with radical chemoradiotherapy (CRT) or radiotherapy (RT). Methods : Overall, 193 patients with ESCC who received radiotherapy with or without chemotherapy at Sichuan Cancer Hospital from March 20, 2012 to December 25, 2017 were retrospectively analysed. Based on serum measurements before treatment, the PNI at ESCC recurrence was calculated as albumin (g/L) + 5 × total lymphocyte count. The Kaplan–Meier method and Cox proportional regression model were used to analyse the relationship between PNI and overall survival (OS). Results : The average pretreatment PNI of 193 ESCC patients was 49.01 ± 4.68. The optimal cutoff value of PNI was 47.975, and the patients were divided into a low-PNI group (<47.975) and a high-PNI group (≥47.975). PNI was related to tumour length, T-stage and synchronous chemotherapy in ESCC patients (P < 0.05). The median OS for the entire group was 22.37 months. The median OS of patients in the high-PNI group and low-PNI group were 32.63 months and 15.4 months, respectively, the 3-year survival rates were 47.5% and 32.2% and the 5-year survival rates were 37.7% and 16.8%, respectively, (all P = 0.001). Univariate analysis showed that PNI, tumour length, T-stage and synchronous chemotherapy were related to the prognosis of ESCC patients (P < 0.05). Multivariate analysis showed that tumour length (P = 0.019), synchronous chemotherapy (P = 0.009) and PNI (P = 0.003) were independent prognostic factors affecting the prognosis of patients in ESCC treated with RT or CRT. Conclusions: The calculation of PNI value is simple, reliable and repeatable and can improve the accuracy of a patient’s prognosis. Confirmation of these results by a large-sample prospective study is desirable.

scholarly journals Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma

2015 ◽  
Vol 47 (3) ◽  
pp. 938-946 ◽  
Author(s):  
Wilko Weichert ◽  
Claudia Kossakowski ◽  
Alexander Harms ◽  
Peter Schirmacher ◽  
Thomas Muley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Cell ◽  
Morphological Characteristics ◽  
Hazard Ratio ◽  
Nuclear Size ◽  
Nest Size ◽  
Prognostic Impact

Recent studies in lung adenocarcinoma established a clinically relevant histomorphology-based classification. In contrast, no morphological classifiers have yet been implemented into routine diagnostics for lung squamous cell carcinoma (SQCC). However, morphology-based characteristics putatively impacting on survival have been proposed.We analysed a cohort of 541 SQCC patients with complete clinical follow-up data for morphological characteristics (keratinisation, tumour cell budding, size of tumour cell nests, nuclear size and stromal content). Morphological characteristics were correlated with clinical data and patient outcome.Keratinisation, budding, stromal content and tumour cell nest size, but not nuclear size, were associated with distinct clinicopathological characteristics and survival. SQCC patients with keratinisation, small cell nest size, high stromal content and extensive budding had shorter overall survival. A combined grading scheme composed of the two most reliable validated prognostic markers,i.e.budding and nest size, resulted in an age-, stage- and sex-independent prognosticator for overall survival with a hazard ratio of 1.6 for grade 2 tumours and a hazard ratio of 3.7 for grade 3 tumours when compared with grade 1 neoplasms (p<0.001).Morphological characteristics of SQCC have significant prognostic impact and could constitute the basis for a diagnostically relevant future SQCC grading scheme.

scholarly journals Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix

2018 ◽  
Vol 4 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Moritz Jesinghaus ◽  
Johanna Strehl ◽  
Melanie Boxberg ◽  
Frido Brühl ◽  
Adrian Wenzel ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Uterine Cervix ◽  
Nest Size ◽  
Tumour Budding

scholarly journals Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells

2021 ◽  
Author(s):  
Zhigeng Zou ◽  
Wei Zheng ◽  
Hongjun Fan ◽  
Guodong Deng ◽  
Shih-Hsin Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
High Throughput Sequencing ◽  
Combined Treatment ◽  
Oesophageal Squamous Cell Carcinoma

Abstract Background Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. Methods We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. Results ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. Conclusions ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.

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