scholarly journals Identification of high protein kinase CK2α in HPV(+) oropharyngeal squamous cell carcinoma and correlation with clinical outcomes

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12519
Author(s):  
Janeen H. Trembley ◽  
Bin Li ◽  
Betsy T. Kren ◽  
Justin Peltola ◽  
Juan Manivel ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Kinase ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Smoking Status ◽  
Mrna Levels ◽  
Ki 67 ◽  
Protein Levels ◽  
Hpv Status

Background Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rising worldwide, especially human papillomavirus (HPV)-associated disease. Historically, high levels of protein kinase CK2 were linked with poor outcomes in head and neck squamous cell carcinoma (HNSCC), without consideration of HPV status. This retrospective study examined tumor CK2α protein expression levels and related clinical outcomes in a cohort of Veteran OPSCC patient tumors which were determined to be predominantly HPV(+). Methods Patients at the Minneapolis VA Health Care System with newly diagnosed primary OPSCC from January 2005 to December 2015 were identified. A total of 119 OPSCC patient tumors were stained for CK2α, p16 and Ki-67 proteins and E6/E7 RNA. CK2α protein levels in tumors and correlations with HPV status and Ki-67 index were assessed. Overall survival (OS) analysis was performed stratified by CK2α protein score and separately by HPV status, followed by Cox regression controlling for smoking status. To strengthen the limited HPV(−) data, survival analysis for HPV(−) HNSCC patients in the publicly available The Cancer Genome Atlas (TCGA) PanCancer RNA-seq dataset was determined for CSNK2A1. Results The patients in the study population were all male and had a predominant history of tobacco and alcohol use. This cohort comprised 84 HPV(+) and 35 HPV(−) tumors. CK2α levels were higher in HPV(+) tumors compared to HPV(−) tumors. Higher CK2α scores positively correlated with higher Ki-67 index. OS improved with increasing CK2α score and separately OS was significantly better for those with HPV(+) as opposed to HPV(−) OPSCC. Both remained significant after controlling for smoking status. High CSNK2A1 mRNA levels from TCGA data associated with worse patient survival in HPV(−) HNSCC. Conclusions High CK2α protein levels are detected in HPV(+) OPSCC tumors and demonstrate an unexpected association with improved survival in a strongly HPV(+) OPSCC cohort. Worse survival outcomes for high CSNK2A1 mRNA levels in HPV(−) HNSCC are consistent with historical data. Given these surprising findings and the rising incidence of HPV(+) OPSCC, further study is needed to understand the biological roles of CK2 in HPV(+) and HPV(−) HNSCC and the potential utility for therapeutic targeting of CK2 in these two disease states.

scholarly journals 837 Preliminary insights into the impact of tumor microbiome in head and neck squamous cell carcinoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A878-A878
Author(s):  
Vidhya Karivedu ◽  
Rebecca Hoyd ◽  
Caroline Wheeler ◽  
Sachin Jhawar ◽  
Priyanka Bhateja ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Smoking History ◽  
Predictive Tool ◽  
Hpv Status ◽  
The Impact

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a heterogeneous set of distinct malignancies. Recognized prognostic factors rely on clinical and biological features, consisting mainly of stage, site of disease, performance status, comorbidities, smoking history and human papilloma virus (HPV) status. However, patients clustered by these parameters still differ in their clinical behavior and therapy response. The impact of the tumor microbiome on human disease has been explored and discussed extensively. Evaluating the tumor microbiome is a promising new approach that could be used as a prognostic and predictive tool in HNSCC, with the potential for improved treatment options and better clinical outcomes.MethodsWe utilized The Cancer Genome Atlas (TCGA) database to obtain RNA sequencing (RNAseq) data to identify microbes in HNSCC samples. We utilized ExoTIC, ”Exogenous sequences in Tumors and Immune cells,” a tool recently developed by Spakowicz et al. ExoTIC takes raw RNAseq reads and carefully aligns them to both human and non-human reference genomes to identify low-abundance microbes. We performed Cox proportional hazards regression to identify the microbes associated with overall survival (OS), controlling for age, stage, and smoking status.ResultsWe evaluated 498 RNAseq samples from TCGA (table 1). ExoTIC identified 5838 microbes including bacteria, viruses and fungi, of which 330 were statistically associated with OS. Interestingly, 20% (n=100) of samples had HPV virus which was significantly associated with improved OS (HR 0.59, CI 0.4–0.9, p<0.01). There were also several other viruses and bacteria associated with significantly improved OS.Abstract 837 Table 1Patient characteristics of TCGA datasetConclusionsWe found the presence of certain microbes in tumor biopsies statistically correlated with OS in HNSCC patients. This supports further study into the presence and correlation of specific microbes with tumor subsite and outcomes. Assessing individual characteristics of a HNSCC subtype with its particular microenvironment (e.g., microbes) can lead to personalized treatment insights and improved outcomes. Our future research will validate and correlate the microbial profile of HNSCC subtypes with clinical outcomes retrospectively and prospectively.

scholarly journals Multiparametric MRI Evaluation of Oropharyngeal Squamous Cell Carcinoma. A Mono-Institutional Study

2021 ◽  
Vol 10 (17) ◽  
pp. 3865
Author(s):  
Francesca Piludu ◽  
Simona Marzi ◽  
Emma Gangemi ◽  
Alessia Farneti ◽  
Laura Marucci ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Smoking Status ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Multivariate Logistic Regression Model ◽  
Primary Tumors ◽  
Dce Mri ◽  
Hpv Status ◽  
Significant Difference

The aim of this paper is to define the pre-treatment radiological characteristics of oropharyngeal squamous cell carcinoma (OPSCC) using morphological and non-morphological magnetic resonance imaging (MRI), based on HPV status, in a single-institution cohort. In total, 100 patients affected by OPSCC were prospectively enrolled in the present study. All patients underwent 1.5T MR with standard sequences, including diffusion-weighted imaging with and intravoxel incoherent motion (IVIM-DWI) technique and a dynamic contrast-enhanced (DCE) MRI. For all patients, human papillomavirus (HPV) status was available. No statistically significant differences in the volume of primary tumors (PTs) and lymph nodes (LNs) were observed based on HPV status. When comparing the two patient groups, no significant differences were found for the PT radiologic characteristics (presence of well-defined borders, exophytic growth, ulceration, and necrosis) and LN morphology (solid/cystic/necrotic). Tumor subsite, smoking status, and alcohol intake significantly differed based on HPV status, as well as ADC and Dt values of both PTs and LNs. We detected no significant difference in DCE-MRI parameters by HPV status. Based on a multivariate logistic regression model, the combination of clinical factors, such as tumor subsite and alcohol habits, with the perfusion-free diffusion coefficient Dt of LNs, may help to accurately discriminate OPSCC by HPV status.

scholarly journals MAGE-A3 is a prognostic biomarker for poor clinical outcome in cutaneous squamous cell carcinoma with perineural invasion via modulation of cell proliferation

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241551
Author(s):  
Aaron Chen ◽  
Alexis L. Santana ◽  
Nicole Doudican ◽  
Nazanin Roudiani ◽  
Kristian Laursen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Perineural Invasion ◽  
Cyclin E ◽  
Normal Skin ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Matrix Metalloproteases ◽  
Mrna Levels

Perineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes. Tumors from these patients expressed high levels of MAGE-A3, a cancer testis antigen that may contribute to key processes of tumor development. In addition to perineural invasion, the tumors exhibited poor differentiation and deep invasion and were subsequently classified as Brigham and Women’s Hospital tumor stage 3. Cyclin E, A and B mRNA levels were increased in these tumors compared with normal skin tissues (102.93±15.03 vs. 27.15±4.59, 36.83±19.41 vs. 11.59±5.83, 343.77±86.49 vs. 95.65±29.25, respectively; p<0.05). A431 cutaneous squamous cell carcinoma cells pretreated with MAGE-A3 antibody exhibited a decreased percentage S-phase cells (14.13±2.8% vs. 33.97±1.1%; p<0.05) and reduced closure in scratch assays (43.88±5.49% vs. 61.17±3.97%; p = 0.0058). In a syngeneic animal model of squamous cell carcinoma, immunoblots revealed overexpression of MAGE-A3 and cyclin E, A, and B protein in tumors at 6 weeks. However, knockout of MAGE-A3 expression caused a reduction in tumor growth (mean tumor volume 155.3 mm3 vs. 3.2 mm3) compared with parental cells. These results suggest that MAGE-A3 is a key mediator in cancer progression. Moreover, elevated collagen XI and matrix metalloproteases 3, 10, 11, and 13 mRNA levels were observed in poorly differentiated cutaneous squamous cell carcinoma with perineural invasion compared with normal skin tissue (1132.56±882.7 vs. 107.62±183.62, 1118.15±1109.49 vs. 9.5±5, 2603.87±2385.26 vs. 5.29±3, 957.95±627.14 vs. 400.42±967.66, 1149.13±832.18 vs. 19.41±35.62, respectively; p<0.05). In summary, this study highlights the potential prognostic value of MAGE-A3 in clinical outcomes of cutaneous squamous cell carcinoma patients.

Comparison of Survival Estimates Following Recurrence, Persistence, or Second Primary Malignancy in Oropharyngeal Squamous Cell Carcinoma

2020 ◽  
Vol 163 (6) ◽  
pp. 1209-1217
Author(s):  
Ameya Asarkar ◽  
José Miguel Flores ◽  
Cherie-Ann O. Nathan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Smoking Status ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Cancer Center ◽  
Second Primary ◽  
Second Primary Malignancy ◽  
Hpv Status ◽  
Disease Free

Objective This study investigated survival among patients with oropharyngeal squamous cell carcinoma (OPSCC) after recurrence, persistence, and second primary malignancies (SPMs). Study Design Retrospective cohort study. Setting Patients were treated at a tertiary cancer center. Subjects and Methods Patients with OPSCC who had completed treatment between 2001 and 2017 were included. Survival estimates of 4 groups of patients were calculated: (1) patients who were disease free after initial treatment, (2) patients who had persistent disease, (3) those with recurrent disease, and (4) patients with SPMs. Cox proportional hazard models and parametric survival analyses (using Weibull distributions) were used to obtain hazard ratios (HRs) and time ratios (TRs). Results The cohort included 364 patients. The crude overall SPM prevalence was 8.2%. Mean overall survival (OS) time in years for patients who remained disease free after treatment was 4.02 years. Among patients who experienced recurrence, the recurrence-free survival (RFS) was 2.58 years while their mean (SD) OS was 3.67 (2.7) years. Participants who experienced persistence had a mean (SD) OS of 1.67 (1.68) years. Patients with observed SPMs had a mean (SD) OS of 6.39 (4.06) years since their primary cancer but shortened survivals of 1.75 (2.34) years since the secondary diagnosis. Differences were present even after accounting for human papillomavirus (HPV) and smoking status. Conclusions Our findings stress the importance of active surveillance as per current National Comprehensive Cancer Network guidelines, irrespective of the HPV status or smoking status. Prospective studies with a larger number of SPM cases and longer follow-up are needed to validate survival trends even beyond 5 years.

scholarly journals Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kate Poropatich ◽  
Tatjana Paunesku ◽  
Alia Zander ◽  
Brian Wray ◽  
Matthew Schipma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Normal Tissue ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Mrna Levels ◽  
Hpv Status ◽  
Trace Elemental ◽  
Increased Sensitivity ◽  
Small Cohort

AbstractHuman papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is biologically distinct from HPV-negative HNSCC. Outside of HPV-status, few tumor-intrinsic variables have been identified that correlate to improved survival. As part of exploratory analysis into the trace elemental composition of oropharyngeal squamous cell carcinoma (OPSCC), we performed elemental quanitification by X-ray fluorescence microscopy (XFM) on a small cohort (n = 32) of patients with HPV-positive and -negative OPSCC and identified in HPV-positive cases increased zinc (Zn) concentrations in tumor tissue relative to normal tissue. Subsequent immunohistochemistry of six Zn-binding proteins—zinc-α2-glycoprotein (AZGP1), Lipocalin-1, Albumin, S100A7, S100A8 and S100A9—revealed that only AZGP1 expression significantly correlated to HPV-status (p < 0.001) and was also increased in tumor relative to normal tissue from HPV-positive OPSCC tumor samples. AZGP1 protein expression in our cohort significantly correlated to a prolonged recurrence-free survival (p = 0.029), similar to HNSCC cases from the TCGA (n = 499), where highest AZGP1 mRNA levels correlated to improved overall survival (p = 0.023). By showing for the first time that HPV-positive OPSCC patients have increased intratumoral Zn levels and AZGP1 expression, we identify possible positive prognostic biomarkers in HNSCC as well as possible mechanisms of increased sensitivity to chemoradiation in HPV-positive OPSCC.

scholarly journals Low GSTM3 expression is associated with poor disease‐free survival in resected esophageal squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fu Yang ◽  
Jing Wen ◽  
Kongjia Luo ◽  
Jianhua Fu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Mrna Levels ◽  
Clinical Prognosis ◽  
Free Survival ◽  
Protein Levels ◽  
Disease Free

Abstract Background Glutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers. However, the relationship between GSTM3 expression and the clinical prognosis of esophageal squamous cell carcinoma (ESCC) has not been studied to date. We aimed to characterize the role of GSTM3 in predicting postoperative prognosis of ESCC patients. Methods In the retrospective study, GSTM3 mRNA levels in 184 ESCC tissues and matched 43 adjacent nontumorous tissues were measured by quantitative real-time PCR. GSTM3 protein levels in 247 ESCC tissues were measured by immunohistochemistry. Results Downregulation of GSTM3 occurred in 62.8 % of primary ESCC tissues compared with their nontumor counterparts. Patients with low GSTM3 expression tended to exhibit an increased rate of poor differentiation in both the mRNA cohort (p = 0.024) and protein cohort (p = 0.004). In the mRNA cohort, low GSTM3 expression was associated with unfavorable 3-year disease-free survival (DFS) (39.2 % vs. 57.4 %) and 5-year DFS (26.8 % vs. 45.1 %) (p = 0.023). The result was confirmed in the protein cohort. Patients with low GSTM3 expression had unfavorable 3-year disease-free survival (DFS) (18.7 % vs. 33.5 %) and 5-year DFS (5.3 % vs. 30.5 %) (p = 0.006). Cox multivariate analysis revealed that GSTM3 expression was an independent prognostic factor. Conclusions The findings of the present study provide evidence that GSTM3 may function as a tumor suppressor in ESCC and represents a potential novel prognostic biomarker for disease-free survival for resected ESCC patients.

scholarly journals Primary squamous cell carcinoma of the pancreas with a large pseudocyst of the pancreas as the first manifestation: a rare case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xia Qiu ◽  
Yajie Meng ◽  
Meiqin Lu ◽  
Chuan Tian ◽  
Min Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Mass ◽  
Elevated Serum ◽  
Abdominal Distension ◽  
Needle Aspiration ◽  
Pancreatic Pseudocysts ◽  
Primary Squamous Cell Carcinoma ◽  
Ki 67

Abstract Background Primary squamous cell carcinoma (SCC) of the pancreas with pseudocysts, especially diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), is extremely rare. Case presentation A 64-year-old man was admitted to our department for abdominal distension. Two months ago, he experienced abdominal pain for 1 day and was diagnosed with acute pancreatitis in another hospital. After admission, laboratory tests showed the following: amylase 400 U/L, lipase 403 U/L, and carbohydrate antigen 19–9 (CA19-9) 347 U/mL. Abdominal computed tomography (CT) revealed pancreatitis with a pseudocyst with a diameter measuring 7 cm. During linear EUS, a large pseudocyst (5.4 × 5.2 cm) was observed in the pancreatic body. EUS-FNA was performed. We obtained specimens for histopathology and placed a plastic stent through the pancreas and stomach to drain the pseudocyst. Puncture fluid examination revealed the following: CA19-9 > 12,000 U/mL carcinoembryonic antigen (CEA) 7097.42 ng/ml, amylase 27,145.3 U/L, and lipase > 6000 U/L. Cytopathology revealed an abnormal cell mass, and cancer was suspected. Furthermore, with the result of immunohistochemistry on cell mass (CK ( +), P40 ( +), p63 ( +), CK7 (−) and Ki-67 (30%)), the patient was examined as squamous cell carcinoma (SCC). However, the patient refused surgery, radiotherapy and chemotherapy. After drainage, the cyst shrank, but the patient died 3 months after diagnosis due to liver metastasis and multiple organ failure. Conclusion For patients with primary pancreatic pseudocysts with elevated serum CEA and CA19-9 levels, we should not rule out pancreatic cancer, which may also be a manifestation of primary pancreatic SCC. EUS-FNA is helpful for obtaining histopathology and cytology and thus improving diagnostic accuracy.

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