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

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 Histopathological Evaluation of Skin Neoplasms

2018 ◽  
Vol 1 (2) ◽  
pp. 89-93
Author(s):  
Palzum Sherpa ◽  
Shiva Raj KC
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Neoplasm ◽  
Skin Neoplasms ◽  
Skin Tumor ◽  
Malignant Neoplasms ◽  
Wide Range ◽  
Histopathological Evaluation ◽  
Intradermal Nevus

Introduction: Skin tumor incidence has increased over the last several decades. A wide range of tumors are encountered in clinical practice. Accurate identification of skin lesions is vital in ensuring malignancies are not missed and that they are treated early to avoid morbidity and mortality.Materials and Methods: A retrospective cross sectional hospital based study on a series of cases was performed in the Department of Pathology, Patan Academy of Health Sciences, Patan Hospital, Lalitpur, Nepal from April 2011 to March 2016. Data from the histopathology database were analyzed using SPSS version 16.0.Results: During the study period, 410 skin biopsies were received, of which 214 (52.2%) were skin neoplasms. Among them, 175 (81.8%) were benign and 39 (18.2%) were malignant neoplasms. Incidence of keratinocytic tumors was highest followed by soft tissue tumors and melanocytic tumors. Intradermal nevus was the most common benign neoplasm. Among the malignant neoplasms, squamous cell carcinoma was most prevalent (46.1%) followed by basal cell carcinoma (15.3%). Skin neoplasms were present in all age groups with maximum number of benign neoplasms prevalent in 21-30 years and malignant in 51-60 years age group. Mean age was 38 years and 58 years for benign and malignant neoplasms respectively.Conclusions: Histopathological evaluation of skin biopsy is an important tool in diagnosis of skin neoplasms. Intradermal nevus and squamous cell carcinoma was the most common benign and malignant neoplasm respectively. Malignant neoplasms were more common in older patients.

scholarly journals Development of Two Types of Skin Cancer in a Patient with Systemic Sclerosis: a Case Report and Overview of the Literature

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Firdevs Ulutaş ◽  
Erdem Çomut ◽  
Veli Çobankara
Keyword(s):  
Systemic Sclerosis ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Case Reports ◽  
Pulmonary Function Tests ◽  
Case Series ◽  
Skin Neoplasms ◽  
Skin Cancers ◽  
Nonspecific Interstitial Pneumonia ◽  
Diffuse Cutaneous Systemic Sclerosis

Systemic sclerosis (SSc) is an uncommon rheumatic disease in which the underlying main histopathologic feature is a thickening of the skin due to excessive accumulation of collagen in the extracellular tissue. Fibrogenesis, chronic inflammation, and ulceration may eventually promote skin neoplasms. Although nonmelanoma skin cancer (NMSC) is the most frequent type, there have been restricted case reports and case series with skin cancers in SSc patients in the literature. Herein, we describe a 78-year-old woman diagnosed with diffuse cutaneous systemic sclerosis thirteen years ago and associated nonspecific interstitial pneumonia that was successfully treated with high cumulative doses of cyclophosphamide. She developed basal cell carcinoma and squamous cell carcinoma of the skin in the follow-up. She is still on rituximab treatment with stable interstitial lung disease as indicated by pulmonary function tests and high-resolution chest computed tomography. To our knowledge and a literature search, this is the first reported patient with SSc with two types of skin cancer. In this review, we also aimed to emphasize the relationship between SSc and skin cancer, and possible risk factors for SSc-related skin cancer.

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.

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