scholarly journals A comparative study of Long Interspersed Element-1 Protein Immunoreactivity in Cutaneous Malignancies

2020 ◽  
Author(s):  
Mohammad Ali Zolfaghari ◽  
Abbas Karimi ◽  
Elham Kalantari ◽  
Alireza Korourian ◽  
Alireza Ghanadan ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Specific Antigen ◽  
Skin Tumor ◽  
Expression Level ◽  
Clinicopathological Parameters ◽  
Cancer Subtypes ◽  
Tumor Subtypes ◽  
Protein Immunoreactivity ◽  
Long Interspersed Element

Abstract Background: Skin cancer is the most common cancer worldwide and commonly classified into malignant melanoma (MM) and Nonmelanoma skin cancers (NMSCs), which mainly include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The extent to which Long Interspersed Element-1 (LINE-1, L1) ORF1p is expressed in cutaneous malignancies remains to be evaluated. This study aimed to assess LINE-1 ORF1p immunoreactivity in various skin cancer subtypes. Method:The expression level of LINE-1 ORF1p was evaluated in 95 skin cancer specimens comprising 36 (37.9%) BCC, 28 (29.5%) SCC, and 31 (32.6%) melanoma using the tissue microarray (TMA) technique. Then the association between expression of LINE-1 encoded protein and clinicopathological parameters was analyzed. Results: We showed that LINE-1 ORF1p expression level was substantially higher in BCC and SCC patients compared with melanoma samples (p < 0.001). BCC cases had a higher LINE-1 histochemical score (H-score) compared with SCC cases (p = 0.004). In SCC samples, a lower level of LINE-1 ORF1p expression was associated with age younger than the mean (p = 0.041). At the same time, no significant correlation was found between LINE-1 ORF1p expression and other clinicopathological parameters (all p > 0.05). Conclusions: According to our observation, LINE-1 ORF1p immunoreactivity in various skin tumor subtypes extends previous studies of LINE-1 expression in different cancers. LINE-1ORF1p overexpression in NMSCs compared with MM can be considered with caution as a tumor-specific antigen for NMSCs.

scholarly journals A comparative study of Long Interspersed Element-1 Protein Immunoreactivity in Cutaneous Malignancies

2019 ◽  
Author(s):  
Mohammad Ali Zolfaghari ◽  
Abbas Karimi ◽  
Elham Kalantari ◽  
Alireza Korourian ◽  
Alireza Ghanadan ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Tissue Microarray ◽  
Specific Antigen ◽  
Skin Neoplasms ◽  
Skin Tumor ◽  
Expression Level ◽  
Clinicopathological Parameters ◽  
Cancer Subtypes ◽  
Long Interspersed Element

Abstract Abstract Background Skin cancer is the most common cancer worldwide and commonly classified into malignant melanoma (MM) and Nonmelanoma skin cancers (NMSCs), which mainly include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The extent to which Long Interspersed Element-1 (LINE-1, L1) ORF1p is expressed in cutaneous malignancies remains to be evaluated. The aim of this study was to assess LINE-1 ORF1p immunoreactivity in various skin cancer subtypes. Method The expression level of LINE-1 ORF1p was evaluated in 95 skin cancer specimens comprising 36 (37.9%) BCC, 28 (29.5%) SCC, and 31 (32.6%) melanoma using the tissue microarray (TMA) technique. Then the association between expression of LINE-1 encoded protein and clinicopathological parameters were analyzed. Results We showed that LINE-1 ORF1p expression level was substantially higher in BCC and SCC patients compared with melanoma samples (p < 0.001). BCC cases had higher LINE-1staining intensity scores compared with SCC cases (p = 0.004). In SCC samples lower level of LINE-1 ORF1p expression was associated with age lower than the mean (p = 0.041), while no significant correlation was found between LINE-1 ORF1p expression and other clinicopathological parameters (all p>0.05). Conclusion : According to our observation, LINE-1 ORF1p immunoreactivity in various skin tumor subtypes extends previous studies of LINE-1 expression in different cancers. LINE-1ORF1p overexpression in NMSCs compared with MM can be considered with caution as a tumor-specific antigen for NMSCs. Keywords: Skin Neoplasms; Retroelements; LINE-1 ORF1p; Immunohistochemistry; Tissue microarray; Biomarker

Comparative Expression Analysis of Putative Cancer Stem Cell Markers CD44 and ALDH1A1 in Various Skin Cancer Subtypes

2016 ◽  
Vol 31 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Elham Erfani ◽  
Raheleh Roudi ◽  
Azadeh Rakhshan ◽  
Mehrdad Nasrollahzadeh Sabet ◽  
Ahmad Shariftabrizi ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Tumor Cells ◽  
Clinicopathological Parameters ◽  
Stem Cell Markers ◽  
Melanoma Tumor ◽  
Expression Levels ◽  
Cancer Subtypes ◽  
Cancer Stem Cell Markers ◽  
Skin Cancers ◽  
Clinicopathological Significance

Introduction Skin cancers, particularly melanoma, are initiated and maintained by a subpopulation of tumor cells expressing stemness markers that are called cancer stem cells (CSCs). This study aimed to evaluate the expression levels and clinicopathological significance of the putative CSC markers CD44 and ALDH1A1 in patients with skin cancer. Methods The expression levels of CD44 and ALDH1A1 were investigated in 107 skin cancer specimens including 58 (54%) basal cell carcinomas (BCC), 37 (35%) squamous cell carcinomas (SCC), and 12 (11%) melanomas using the tissue microarray (TMA) technique. The correlation of the expression levels of these markers and clinicopathological parameters was then analyzed. Results The expression levels of CD44 and ALDH1A1 were significantly higher in melanoma patients than patients with SCC or BCC (p<0.001 and p = 0.002, respectively). A higher level of CD44 expression was more often found in melanoma tumor cells with a higher rate of recurrence (p = 0.029) and in SCC cases with ulceration (p = 0.01), while there was no significant correlation between ALDH1A1 expression and other clinicopathological parameters. Similarly, coexpression of CD44 and ALDH1A1 (CD44high/ALDH1A1high) was significantly observed in melanoma samples (p<0.001). Conclusions These findings suggest that a CD44high/ALDH1A1high phenotype in melanoma and a CD44high phenotype in SCC can be considered candidates for targeted therapy of skin cancers aiming at CSCs.

scholarly journals CYTOLOGICAL DIAGNOSTICS OF MERKEL CELL CARCINOMA (PRIMARY NEURO-ENDOCRINE SKIN CANCER) IN THE MATERIAL OF A SUPERFICIAL SHAVE BIOPSY

2021 ◽  
pp. 54-58
Author(s):  
V. N. Vysotskaya ◽  
Y. V. Karpova ◽  
E. S. Sukhovskaya ◽  
A. V. Babushkin ◽  
Ni. V. Boriskin
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Neuroendocrine Differentiation ◽  
Skin Tumor ◽  
Merkel Cell ◽  
Cytological Method ◽  
Cytological Diagnostics

Merkel cell carcinoma is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. In the presented diagnostic case, the possibility of a cytological method in this material is a scarification biopsy.

scholarly journals Targeting 14-3-3ε activates apoptotic signaling to prevent cutaneous squamous cell carcinoma

2020 ◽  
Author(s):  
Thomas R Holmes ◽  
Jenan Al Matouq ◽  
Matti Holmes ◽  
Natasha Sioda ◽  
Justin C Rudd ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Development ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Malignant Progression ◽  
Skin Tumor ◽  
Premalignant Lesions

Abstract More than a million cases of cutaneous squamous cell carcinoma are diagnosed in the USA each year, and its incidence is increasing. Most of these malignancies arise from premalignant lesions, providing an opportunity for intervention before malignant progression. We previously documented how cytoplasmic mislocalization of CDC25A in premalignant and malignant skin cancers confers resistance to apoptotic cell death via a mechanism that depends on its interaction with 14-3-3ε. From these data, we hypothesized that 14-3-3ε overexpression drives skin tumor development and progression, such that targeting 14-3-3ε may be a useful strategy for skin cancer treatment. Like CDC25A, 14-3-3ε was overexpressed and mislocalized to the cytoplasm of both benign and malignant human skin cancer. Skin-targeted deletion of the 14-3-3ε gene reduced skin tumor development by 75% and blocked malignant progression. 14-3-3ε suppressed apoptosis through activation of Akt, leading to inhibition of BCL2 associated agonist of cell death and upregulation of Survivin. Using virtual tetrapeptide libraries, we developed a novel peptide that specifically blocked 14-3-3ε heterodimerization and thereby prevented its interaction with CDC25A. The peptide reduced prosurvival signaling, killed skin cancer cells and reduced skin tumor growth in xenograft. Normal skin keratinocytes were unaffected by inhibition or deletion of 14-3-3ε. Thus, targeting of 14-3-3ε dimerization is a promising strategy for the treatment of premalignant skin lesions.

scholarly journals Exploring Various Polygenic Risk Scores for Skin Cancer in the Phenomes of the Michigan Genomics Initiative and the UK Biobank with a Visual Catalog:PRSWeb

2018 ◽  
Author(s):  
Lars G. Fritsche ◽  
Lauren J. Beesley ◽  
Peter VandeHaar ◽  
Robert B. Peng ◽  
Maxwell Salvatore ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Genetic Risk ◽  
Population Based ◽  
Risk Scores ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Cancer Subtypes ◽  
Construction Methods ◽  
The Uk

AbstractPolygenic risk scores (PRS) are designed to serve as a single summary measure, condensing information from a large number of genetic variants associated with a disease. They have been used for stratification and prediction of disease risk. The construction of a PRS often depends on the purpose of the study, the available data/summary estimates, and the underlying genetic architecture of a disease. In this paper, we consider several choices for constructing a PRS using summary data obtained from various publicly-available sources including the UK Biobank and evaluate their abilities to predict outcomes derived from electronic health records (EHR). Weexamine the three most common skin cancer subtypes in the USA: basal cellcarcinoma, cutaneous squamous cell carcinoma, and melanoma. The genetic risk profiles of subtypes may consist of both shared and unique elements and we construct PRS to understand the common versus distinct etiology. This study is conducted using data from 30,702 unrelated, genotyped patients of recent European descent from the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort within Michigan Medicine. Using these PRS for various skin cancer subtypes, we conduct a phenome-wide association study (PheWAS) within the MGI data to evaluate their association with secondary traits. PheWAS results are then replicated using population-based UK Biobank data. We develop an accompanying visual catalog calledPRSwebthat provides detailed PheWAS results and allows users to directly compare different PRS construction methods. The results of this study can provide guidance regarding PRS construction in future PRS-PheWAS studies using EHR data involving disease subtypes.Author summaryIn the study of genetically complex diseases, polygenic risk scores synthesize information from multiple genetic risk factors to provide insight into a patient’s risk of developing a disease based on his/her genetic profile. These risk scores can be explored in conjunction with health and disease information available in the electronic medical records. They may be associated with diseases that may be related to or precursors of the underlying disease of interest. Limited work is available guiding risk score construction when the goal is to identify associations across the medical phenome. In this paper, we compare different polygenic risk score construction methods in terms of their relationships with the medical phenome. We further propose methods for using these risk scores to decouple the shared and unique genetic profiles of related diseases and to explore related diseases’ shared and unique secondary associations. Leveraging and harnessing the rich data resources of the Michigan Genomics Initiative, a biorepository effort at Michigan Medicine, and the larger population-based UK Biobank study, we investigated the performance of genetic risk profiling methods for the three most common types of skin cancer: melanoma, basal cell carcinoma and squamous cell carcinoma.

scholarly journals AIRE is induced in oral squamous cell carcinoma and promotes cancer gene expression

2019 ◽  
Author(s):  
Chi Thi Kim Nguyen ◽  
Wanlada Sawangarun ◽  
Masita Mandasari ◽  
Kei-ichi Morita ◽  
Kou Kayamori ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Nuclear Translocation ◽  
Specific Antigen ◽  
Constitutive Expression ◽  
Skin Tumor ◽  
Tissue Specimens

AbstractAutoimmune regulator (AIRE) is a transcriptional regulator that is primarily expressed in medullary epithelial cells, where it induces tissue-specific antigen expression. Under pathological conditions, AIRE expression is induced in epidermal cells and promotes skin tumor development in association with stress-responsive keratin KRT17. This study aimed to clarify the role of AIRE in the pathogenesis of oral squamous cell carcinoma (OSCC). AIRE expression was evaluated in seven OSCC cell lines and in OSCC tissue specimens. Transient or constitutive expression of AIRE in 293A cells induced KRT17 expression. cDNA microarray analysis of 293A cells stably expressing AIRE revealed that STAT1 and ICAM1 were significantly upregulated by AIRE. Expression of KRT17, STAT1, ICAM1, MMP9, CXCL10, and CXCL11 was elevated in 293A cells stably expressing AIRE, and conversely, was decreased in AIRE-knockout HSC3 OSCC cells when compared to the respective controls. Upregulation of KRT17, STAT1, and ICAM in OSCC cells was confirmed in tissue specimens by immunohistochemistry. We provide evidence that AIRE exerts transcriptional control in cooperation with ETS1. Expression of STAT1, ICAM1, CXCL10, and MMP9 was increased in 293A cells upon Ets1 transfection, and coexpression of AIRE resulted in enhanced expression of STAT1. AIRE coprecipitated with ETS1 in a modified immunoprecipitation assay using formaldehyde crosslinking. Chromatin immunoprecipitation and quantitative PCR analysis revealed that promoter fragments of STAT1, ICAM1, CXCL10, and MMP9 were enriched in the AIRE precipitates. In oral cancer cells, ETS1 was diffusely located in the nucleus and partially overlapped with dot-like AIRE accumulation sites. Nuclear translocation of AIRE was promoted by cotransfection with Ets1. These results indicate that AIRE is induced in OSCC and supports cancer-related gene expression in cooperation with ETS1. This is a novel function of AIRE in extrathymic tissues under the pathological condition.

scholarly journals Cytoplasmic Increase of Hsp70 Protein: Potential New Biomarker of Early Infiltration of Cutaneous Squamous Cell Carcinoma Arising from Actinic Keratosis

2020 ◽  
Author(s):  
Montserrat Fernandez-Guarino ◽  
José Javier Zamorano León ◽  
Antonio José López Farré ◽  
Maria Luisa Gonzalez Morales ◽  
Ana Isabel Sanchez Adrada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Heat Shock ◽  
Skin Cancer ◽  
Heat Shock Protein ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Actinic Keratosis ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Expression Level ◽  
Hsp70 Protein

Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non- melanoma skin cancer and the second cause of death by skin cancer in caucasian population. However, at present it is difficult to predict patients with worst SCC prognosis. Objective: To identify proteins whose expression level could predict SCC infiltration in SCC arising from actinic keratosis (AC). Methods: A total of 20 biopsies of 20 different patients were studied, 10 were from SCC-AK samples and 10 from normal skin. Early infiltrated SCC-AK were selected on histological examination and to determine the expression of proteins fresh skin samples were processed by 2DE-electrophoresis Results: The expression levels of three proteins namely alpha-hemoglobin, heat shock protein (Hsp)-27 and 70 were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immnunohistological examination suggested that the increased expression of Hsp70 proteins seems to mainly occur in the keratinocytes cytoplasm. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western-blot experiments. Conclusion: Cytoplasmic expression of Hsp70 could be potential biomarker of early infiltration of SCC arising from an AK. Keywords: actinic keratosis, cutaneous squamous cell carcinoma; cytoplasm, skin cancer; heat shock protein.

scholarly journals Surgeon Experience Level and Number of Mohs Stages: A Prospective Observational Study of In-training Surgeons

2021 ◽  
Vol 5 (5) ◽  
pp. 496-502
Author(s):  
Michael Visconti ◽  
Molly Buckland ◽  
Kent Krach ◽  
Adam Richardson ◽  
Veronica Rutt
Keyword(s):  
Skin Cancer ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Experience Level ◽  
Cancer Subtypes ◽  
Surgeon Experience ◽  
The Mean ◽  
Superficial Basal Cell Carcinoma ◽  
Respective Number

Background Comparisons of Mohs surgeons by experience level (early-, mid-, late-career) and their respective number of stages taken during Mohs have not detected any difference. However, data comparing the number of stages for attending Mohs surgeons to Mohs fellows is non-existent. Objective To prospectively observe and compare the mean number of Mohs stages taken for attending Mohs surgeons and fellows. Methods/Materials Procedural data from 2,140 Mohs cases over 24 months was collected and divided into an attending or fellow surgeon cohort. Results The attending cohort had a higher mean number of stages for all nonmelanoma skin cancer when compared to the fellow cohort (p=0.005). The attending cohort demonstrated a higher mean number of stages for non-aggressive, non-superficial basal cell carcinoma (p<0.001), but no difference was found for other cancer subtypes. No difference was detected when comparing the two cohorts’ performance at high, medium, and low risk surgical areas. Conclusion The attending cohort had a higher mean number of stages overall for combined types of skin cancer and for non-aggressive, non-superficial basal cell carcinoma specifically when stratified by diagnosis as compared to the fellow cohort. No difference existed in the mean number of stages between the cohorts based on surgical area.

A Comprehensive Review on Nanotechnology-Based Innovations in Topical Drug Delivery for the Treatment of Skin Cancer

2020 ◽  
Vol 26 (44) ◽  
pp. 5720-5731 ◽  
Author(s):  
Arun Singh Lalotra ◽  
Vishesh Singh ◽  
Bharat Khurana ◽  
Shelly Agrawal ◽  
Shubham Shrestha ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Systemic Exposure ◽  
Chemotherapeutic Agents ◽  
The Body ◽  
Toxic Substances ◽  
Abnormal Growth ◽  
Dermal Layer ◽  
Therapeutic Benefits ◽  
Carrier Systems

Background: Skin is the largest organ of the body and helps to regulate several physiological functions. It acts as a barrier that protects the body against UV-radiation, toxic substances, infections, etc. The abnormal growth of the skin cells is called skin cancer. Different types of skin cancer can be classified as Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC); which mainly occur due to chronic exposure to UV- sunlight and pollution. Methods: The conventional topical treatments of skin cancer such as cream, gel, ointment, etc., are more occlusive and thus they do not penetrate deep into the skin (dermal layer) and remain at the upper part of the skin (epidermal layer). The stratum corneum acts as a physiological barrier for the drug-loaded in the conventional formulation. The novel carrier systems have the potential to facilitate the penetration of the drug deep into the skin (dermal layer) because these have less size and higher flexibility than conventional treatment. Conclusion: In the present review, we have discussed various novel carrier systems being investigated for the topical application of chemotherapeutic agents for efficient skin targeting and better dermatological as well as therapeutic benefits with minimal systemic exposure and toxicity.

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