scholarly journals Necroptosis in Esophageal Squamous Cell Carcinoma: An Independent Prognostic Factor and Its Correlation with Tumor-Infiltrating Lymphocytes

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4473
Author(s):  
Takuro Yamauchi ◽  
Fumiyoshi Fujishima ◽  
Masatoshi Hashimoto ◽  
Junichi Tsunokake ◽  
Ryujiro Akaishi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factor ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Efficacy ◽  
Tumor Infiltrating Lymphocytes ◽  
Independent Prognostic Factor ◽  
Biopsy Specimens ◽  
Infiltrating Lymphocytes

Necroptosis is a pivotal process in cancer biology; however, the clinical significance of necroptosis in esophageal squamous cell carcinoma (ESCC) has remained unknown. Therefore, in this study, we aimed to verify the potential involvement of necroptosis in the clinical outcome, chemotherapeutic resistance, and tumor microenvironment of ESCC. Mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunohistochemically examined in 88 surgically resected specimens following neoadjuvant chemotherapy (NAC) and 53 pre-therapeutic biopsy specimens, respectively. Tumor-infiltrating lymphocytes (TILs) were also evaluated by immunolocalizing CD3, CD8, and forkhead box protein 3 (FOXP3) in the residual tumors after NAC. High pMLKL status in the post-NAC resected specimens was significantly correlated with worse prognosis in ESCC patients. Multivariate analysis demonstrated that a high pMLKL status was an independent prognostic factor. In pre-NAC biopsy specimens, a high pMLKL status was significantly associated with a lower therapeutic efficacy. CD8+ TILs were significantly lower in the high-pMLKL group. FOXP3+ TILs were significantly higher in both high-MLKL and high-pMLKL groups. We first demonstrated pMLKL status as an independent prognostic factor in ESCC patients. Our study revealed the possible involvement of necroptosis in the immunosuppressive microenvironment, resulting in the attenuated therapeutic efficacy of NAC and eventual adverse clinical outcomes in ESCC.

scholarly journals Novel Pathological Predictive Factors for Extranodal Extension in Oral Squamous Cell Carcinoma: a Retrospective Cohort Study Based on Tumor Budding, Desmoplastic Reaction, and Tumor-infiltrating Lymphocytes

2021 ◽  
Author(s):  
Yuri Noda ◽  
Mitsuaki Ishida ◽  
Yasuhiro Ueno ◽  
Takuo Fujisawa ◽  
Hiroshi Iwai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Desmoplastic Reaction ◽  
Extranodal Extension ◽  
Biopsy Specimens ◽  
Infiltrating Lymphocytes

Abstract Background: Extranodal extension (ENE) is a poor prognostic factor for oral squamous cell carcinoma (OSCC). Identifying ENE by clinical and/or radiological examination is difficult, thereby leading to unnecessary neck dissections. Currently, no definitive predictors are available for ENE. Thus, we aimed to determine the histological predictors of ENE by routine histopathological examination using biopsy and surgically resected specimens.Methods: This retrospective study included 186 surgically resected OSCC and 83 matched biopsy specimens. Clinical features associated with the tumor microenvironment, including desmoplastic reaction (DR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs), were evaluated using hematoxylin and eosin-stained primary OSCC and neck dissection specimens. These histological features were divided into two groups: DR-immature (DR-I) and DR-mature (DR-M); TB-high (TB-H) and TB-low (TB-L); and TILs-low (TILs-L) and TILs-high (TILs-H). Clinical depth of invasion (cDOI) and pathological DOI (pDOI) were adapted for biopsies and resections, respectively; DOI was evaluated as DOI >10 mm and DOI ≤10 mm. The clinicopathological relationships between these histopathological features and ENE and the independent risk factors for ENE were analyzed. The histological predictors of ENE were evaluated.Results:The histological status of DR, TILs, and TB present in biopsy and resection specimens showed high accuracy with that of ENE. DR-I, TILs-L, and TB-H were significantly associated with lymph node metastasis, cDOI, and pDOI. Bivariate and multivariate analyses revealed that TB-H and pDOI >10 mm in resections were independent factors for the presence of ENE (ENE+). The combination of TB-H/pDOI >10 mm in resection specimens showed high specificity (91%) and accuracy (83%) regarding ENE+. Although there proved to be no independent factors in biopsies, DR-I and TILs-L were significantly associated with ENE+ (p<0.001). The combination of DR-I/TILs-L/cDOI >10 mm in biopsies exhibited high sensitivity and specificity with ENE+ (70% and 77%, respectively, p<0.001). These histological predictors could detect even minor ENE (<2 mm).Conclusions:The tumor microenvironment status in primary OSCC was significantly associated with that of ENE, and TB-H was an independent risk factor for ENE. The histological status of DR-I/TILs-L/cDOI >10 mm in biopsy specimens and TB-H/pDOI >10 mm in resection specimens is a useful predictor of ENE.

PGP9.5 Promoter Methylation Is an Independent Prognostic Factor for Esophageal Squamous Cell Carcinoma

2005 ◽  
Vol 65 (11) ◽  
pp. 4963-4968 ◽  
Author(s):  
Diana L. Mandelker ◽  
Keishi Yamashita ◽  
Yutaka Tokumaru ◽  
Koshi Mimori ◽  
David L. Howard ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factor ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Promoter Methylation ◽  
Independent Prognostic Factor

scholarly journals CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3982
Author(s):  
Yen-Hao Chen ◽  
Hung-I Lu ◽  
Chien-Ming Lo ◽  
Shau-Hsuan Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factor ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Independent Prognostic Factor ◽  
Expression Levels ◽  
Invasion And Migration ◽  
Patient Responses

Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy, including 64 and 103 patients with high and low expression levels of CD73, respectively. Univariate and multivariate analyses showed high expression of CD73 was an independent prognostic factor for worse disease-free survival and overall survival. In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. Moreover, the transwell assay revealed knockdown of CD73 in two ESCC cell lines, TE1 and KYSE30, exhibited significantly reduced abilities of cell invasion and migration. CD73 silencing also showed that the protein expression levels of CD73, vimentin, and snail were downregulated, while those of E-cadherin were upregulated in Western blotting. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy.

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