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Journal of Dermatological Science Feb 2020NUAK2 is a critical gene that participates in the carcinogenesis of various types of cancers including melanomas. However, the expression patterns of NUAK2 in normal...
BACKGROUND
NUAK2 is a critical gene that participates in the carcinogenesis of various types of cancers including melanomas. However, the expression patterns of NUAK2 in normal skin and in various types of skin tumors have not been fully elucidated to date.
OBJECTIVES
To elucidate the distribution and localization of NUAK2 expression in normal skin, and characterize the expression patterns of NUAK2 and YAP in various types of skin tumors.
METHODS
In this study, we characterized the expression of NUAK2 in tissues by developing a novel NUAK2-specific monoclonal antibody and using that to determine NUAK2 expression patterns in normal skin and in 155 cases of various types of skin tumors, including extramammary Paget's disease (EMPD), squamous cell carcinoma (SCC), Bowen's disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC) and angiosarcoma (AS). Further, we analyzed the expression patterns of YAP and p-Akt in those tumors.
RESULTS
Our analyses revealed that NUAK2 is expressed at high frequencies in EMPD, SCC, BD, AK, BCC and AS. The expression of p-Akt was positively correlated with tumor size in EMPD (P = 0.001). Importantly, the expression of NUAK2 was significantly correlated with YAP in SCC (P = 0.012) and in BD (P = 0.009).
CONCLUSIONS
Our results suggest that the YAP-NUAK2 axis has critical importance in the tumorigenesis of SCC and BD, and that therapeutic modalities targeting the YAP-NUAK2 axis may be an effective approach against skin tumors including SCC and BD.
Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Bowen's Disease; Carcinogenesis; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Protein Serine-Threonine Kinases; Retrospective Studies; Signal Transduction; Skin; Skin Neoplasms; Transcription Factors; YAP-Signaling Proteins
PubMed: 32001115
DOI: 10.1016/j.jdermsci.2020.01.008 -
Communications Biology Aug 2022The Frankfurt specimen of the early-branching ceratopsian dinosaur Psittacosaurus is remarkable for the exquisite preservation of squamous (scaly) skin and other soft... (Review)
Review
The Frankfurt specimen of the early-branching ceratopsian dinosaur Psittacosaurus is remarkable for the exquisite preservation of squamous (scaly) skin and other soft tissues that cover almost its entire body. New observations under Laser-Stimulated Fluorescence (LSF) reveal the complexity of the squamous skin of Psittacosaurus, including several unique features and details of newly detected and previously-described integumentary structures. Variations in the scaly skin are found to be strongly regionalized in Psittacosaurus. For example, feature scales consist of truncated cone-shaped scales on the shoulder, but form a longitudinal row of quadrangular scales on the tail. Re-examined through LSF, the cloaca of Psittacosaurus has a longitudinal opening, or vent; a condition that it shares only with crocodylians. This implies that the cloaca may have had crocodylian-like internal anatomy, including a single, ventrally-positioned copulatory organ. Combined with these new integumentary data, a comprehensive review of integument in ceratopsian dinosaurs reveals that scalation was generally conservative in ceratopsians and typically consisted of large subcircular-to-polygonal feature scales surrounded by a network of smaller non-overlapping polygonal basement scales. This study highlights the importance of combining exceptional specimens with modern imaging techniques, which are helping to redefine the perceived complexity of squamation in ceratopsians and other dinosaurs.
Topics: Animals; Carcinoma, Squamous Cell; Dinosaurs; Fossils; Preservation, Biological; Skin
PubMed: 35962036
DOI: 10.1038/s42003-022-03749-3 -
Acta Otorhinolaryngologica Italica :... Feb 2020
Review
Topics: Carcinoma, Basal Cell; Disease Management; Face; Head; Head and Neck Neoplasms; Humans; Otolaryngology; Risk Factors; Skin; Skin Neoplasms; Surgeons
PubMed: 31388193
DOI: 10.14639/0392-100X-2245 -
Clinical and Experimental Dermatology Nov 2022Literature on the dermoscopic patterns of basal cell carcinoma (BCC) in India is limited.
BACKGROUND
Literature on the dermoscopic patterns of basal cell carcinoma (BCC) in India is limited.
AIM
To describe the dermoscopic pattern and dermoscopic-histopathological correlation in a large cohort of patients with BCC from India, with a particular focus on skin of colour (SOC).
METHODS
This retrospective study was conducted under the aegis of the Dermatoscopy Society of India. Clinical details were collected, and two lead authors independently analysed dermoscopic images of BCC for a predefined set of characteristics. Histopathological slides/blocks were reviewed, and dermoscopic-histological correlation attempted.
RESULTS
In total, 143 patients with BCC and skin phototypes IV-VI were included. The mean largest BCC diameter was 3.10 ± 3.68 cm and there was a significant but weak association between duration and largest dimension of the lesion (Spearman ρ = 0.33, P < 0.01). Nearly half of the cases were diagnosed with pigmented BCC and the most common histological subtype was nodular BCC (37.9%). Dermoscopically, blue-grey dots and arborizing vessels were the most common features (60.0%). Pigmentary changes were found in the majority of cases, and included blue-white veil, blue-grey ovoid nests and maple leaf-like areas. A third of our patients had short linear telangiectasia, polymorphic vessels and regular dotted vessels, and another third exhibited a dermoscopic rainbow effect. Arborizing vessels were significantly more common with micronodular (78.9%) and nodular variants (74.1%, P = 0.05), whereas regular dotted vessels (68.4%, P = 0.04), blue-white veil (84.2%, P = 0.02) were significantly associated with micronodular variant.
CONCLUSION
The dermoscopic patterns of blue-white veil and regular dotted vessels are indicators towards micronodular BCC in SOC and can help in prioritizing treatment.
Topics: Humans; Dermoscopy; Retrospective Studies; Skin Neoplasms; Carcinoma, Basal Cell; Skin
PubMed: 35867028
DOI: 10.1111/ced.15337 -
American Journal of Clinical Dermatology May 2022Actinic keratosis (AK) is a chronic skin disease in which clinical and subclinical cutaneous lesions coexist on sun-exposed areas such as the head and neck region and... (Review)
Review
Actinic keratosis (AK) is a chronic skin disease in which clinical and subclinical cutaneous lesions coexist on sun-exposed areas such as the head and neck region and the extremities. The high prevalence of AK means the disease burden is substantial, especially in middle-aged and elderly populations. Evidence indicates that AK may progress into invasive cutaneous squamous cell carcinoma, so the European guidelines recommend treatment of any AK regardless of clinical severity. Given the aging population and therefore the increasing incidence of AK and cutaneous field carcinogenesis, further updates on the long-term efficacy of current therapies and new investigational agents are critical to guide treatment choice. Patients often have difficulty adequately applying topical treatments and coping with adverse local skin reactions, leading to less than optimum treatment adherence. The development of associated local skin symptoms and cosmetic outcomes for the area of interest are also relevant to the choice of an appropriate therapeutic strategy. Treatment is always individually tailored according to the characteristics of both patients and lesions. This review focuses on the therapeutic approaches to AK and illustrates the currently available home-based and physician-managed treatments.
Topics: Administration, Topical; Aged; Carcinoma, Squamous Cell; Humans; Keratosis, Actinic; Middle Aged; Skin; Skin Neoplasms
PubMed: 35182332
DOI: 10.1007/s40257-022-00674-3 -
Journal of Dermatological Science Jul 2020Cutaneous squamous cell carcinoma (cSCC) and its precursors, actinic keratosis (AK) and Bowen's disease (BD), are the most common types of keratinocytic skin lesions... (Review)
Review
Cutaneous squamous cell carcinoma (cSCC) and its precursors, actinic keratosis (AK) and Bowen's disease (BD), are the most common types of keratinocytic skin lesions (KSL) which account for the majority of non-melanoma skin cancer lethality. Currently, clinical and histopathological criteria are used for the diagnosis, classification and therapeutic intervention of KSLs, however discrepancies exist between the clinical presentations and histologic analyses of these lesions, making the diagnosis difficult. The identification of biomarkers as companion diagnostics for accurately stratifying KSL types is required to support the paradigm shift in current cancer care to personalised, precision medicine and ameliorate the negative impact of misdiagnoses or delayed diagnoses on patient outcome. Also, it is essential to elaborate on the poorly defined molecular modifications required for the initiation, development and progression of KSL from normal keratinocytes. By harnessing recent technological advances in molecular profiling techniques, it is anticipated that greater insight into the various combinations of proteomic events or alternative pathways underlying carcinogenesis will be gained. This review will explore recent genomic studies in KSL followed by assessing the feasibility and significance of mass spectrometry-based proteomics profiling as a promising approach to a better understanding of the oncogenic pathways underpinning the formation and progression of KSL lesions and in aiding the identification of novel biomarkers and new therapeutic targets. The development of non-invasive tools such as tape-stripping coupled with proteomic analysis alone or in conjunction with imaging and genomic technologies will complement existing clinical and histopathological parameters, leading to an improvement in patient outcomes.
Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Delayed Diagnosis; Diagnostic Errors; Gene Expression Profiling; Humans; Keratosis, Actinic; Proteomics; Skin; Skin Neoplasms
PubMed: 32312638
DOI: 10.1016/j.jdermsci.2020.03.008 -
Journal of the European Academy of... Apr 2023Machine learning (ML) models for skin cancer recognition may have variable performance across different skin phototypes and skin cancer types. Overall performance... (Review)
Review
Machine learning (ML) models for skin cancer recognition may have variable performance across different skin phototypes and skin cancer types. Overall performance metrics alone are insufficient to detect poor subgroup performance. We aimed (1) to assess whether studies of ML models reported results separately for different skin phototypes and rarer skin cancers, and (2) to graphically represent the skin cancer training datasets used by current ML models. In this systematic review, we searched PubMed, Embase and CENTRAL. We included all studies in medical journals assessing an ML technique for skin cancer diagnosis that used clinical or dermoscopic images from 1 January 2012 to 22 September 2021. No language restrictions were applied. We considered rarer skin cancers to be skin cancers other than pigmented melanoma, basal cell carcinoma and squamous cell carcinoma. We identified 114 studies for inclusion. Rarer skin cancers were included by 8/114 studies (7.0%), and results for a rarer skin cancer were reported separately in 1/114 studies (0.9%). Performance was reported across all skin phototypes in 1/114 studies (0.9%), but performance was uncertain in skin phototypes I and VI from minimal representation of the skin phototypes in the test dataset (9/3756 and 1/3756, respectively). For training datasets, although public datasets were most frequently used, with the most widely used being the International Skin Imaging Collaboration (ISIC) archive (65/114 studies, 57.0%), the largest datasets were private. Our review identified that most ML models did not report performance separately for rarer skin cancers and different skin phototypes. A degree of variability in ML model performance across subgroups is expected, but the current lack of transparency is not justifiable and risks models being used inappropriately in populations in whom accuracy is low.
Topics: Humans; Skin Neoplasms; Carcinoma, Basal Cell; Melanoma; Skin; Carcinoma, Squamous Cell
PubMed: 36514990
DOI: 10.1111/jdv.18814 -
Experimental Dermatology Oct 2023As extramammary Paget's disease (EMPD) sometimes invades and metastasizes from the skin to the mucosa, radical surgical resection of these lesions is often difficult.... (Review)
Review
As extramammary Paget's disease (EMPD) sometimes invades and metastasizes from the skin to the mucosa, radical surgical resection of these lesions is often difficult. The purpose of this study was to analyse the association between surgical margins and survival as well as the benefit of functional preservation over complete resection, in patients with EMPD. We retrospectively analysed 230 patients diagnosed with EMPD between 1969 and 2020. Patient and treatment characteristics were recorded. Since our centre is a specialized hospital and almost all patients were referred from other hospitals, we reviewed their referral letters. Prognostic factors and survival time were also analysed. Among 230 patients, 78 (33.9%) had positive margins. The presence of margin positive lesions increased the local recurrence rate but was not significantly correlated with survival. Of all the patients who had received a thorough explanation about the surgical procedure in the referring hospital, 43.8% were scheduled for surgeries that would result in functional impairment, and all of them had function-preserving surgeries at our hospital with a 10-year survival rate of 100%. Our result suggest that less invasive surgery preserves anogenital and urethral function may be an acceptable option for EMPD treatment.
Topics: Humans; Paget Disease, Extramammary; Retrospective Studies; Margins of Excision; Skin
PubMed: 37377183
DOI: 10.1111/exd.14866 -
Anticancer Research Jul 2020Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study,... (Observational Study)
Observational Study
BACKGROUND/AIM
Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step.
PATIENTS AND METHODS
We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC.
RESULTS
KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria.
CONCLUSION
KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.
Topics: Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Kidney Transplantation; Middle Aged; Skin; Skin Neoplasms
PubMed: 32620646
DOI: 10.21873/anticanres.14396 -
Journal of Cutaneous Pathology Aug 2021Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue....
Secretory carcinoma of the skin is an extremely rare adnexal tumor, histopathologically identical to homologous lesions in the salivary glands and breast tissue. Although this tumor was previously reported as indolent, we report a case of secretory carcinoma of the skin with metastases and recurrence. The patient, a 31-year-old women, had a subcutaneous mass in the right axilla. The resected specimen contained a circumscribed mass, with proliferating tumor cells that exhibited prominent nucleoli. They exhibited glandular and papillary growth patterns and there were amphophilic secretions in the glands. Immunohistochemically, the tumor cells were positive for mammaglobin and S100. The tumor was surrounded by sweat glands and there was no mammary glandular tissue, suggesting that it was derived from axillary sweat glands. Accordingly, we made a diagnosis of secretory carcinoma of the skin. Four years after the operation, there were metastases in both lungs. The resected specimen revealed a tumor identical to that of the original skin tumor. Next-generation sequencing-based multiplex gene assay performed on the metastatic tissue revealed an ETV6-NTRK3 fusion gene. This is a rare case report of secretory carcinoma of the skin with lymph node metastases and recurrence in both lungs.
Topics: Adult; Diagnosis, Differential; Female; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Lung Neoplasms; Lymphatic Metastasis; Mammary Analogue Secretory Carcinoma; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; S100 Proteins; Secretoglobins; Skin Neoplasms; Sweat Glands; Thoracic Surgery, Video-Assisted
PubMed: 33882152
DOI: 10.1111/cup.14028