Basal Cell Carcinoma Cells Research Articles

Report of 3 Cases Diagnosed with Basal Cell Carcinoma and Systemic Mastocytosis with Favorable Prognosis

Abstract Introduction/Objective The co-existence of basal cell carcinoma (BCC) and systemic mastocytosis is an exceptionally rare clinical occurrence, and the prognosis is not well-documented. Understanding the clinical and histopathological features of this uncommon association is relevant for accurate diagnosis, management, and prognostication. Methods/Case Report We conducted a retrospective analysis of three cases of BCC with concurrent systemic mastocytosis that were identified in the pathology database of the University of Pennsylvania from 2010 to 2023. Patient demographics, clinical and histopathologic characteristics, and treatment outcomes were reviewed. Histopathologic assessment, immunohistochemistry, and C-KIT D816V mutation analysis (with an allele-specific PCR assay) were performed on biopsy material. Next-Generation Sequencing (NGS) was used to identify other hematologic neoplasm-associated mutations. Results (if a Case Study enter NA) All three cases were female with a median age of 55.3 years (50, 69, 47). In all three cases, atypical CD117+ tryptase+ CD25+ mast cells with mild to moderate pleomorphism were found in the dermis adjacent to the BCC cells. All three cases had bone marrow involvement. Serum tryptase levels were mildly elevated in all 3 patients (maximum 65.5 μg/L). All three cases harbor a C-KIT D816V mutation and a history of systemic glucocorticosteroids before the diagnosis of BCC. One of the cases was treated with phototherapy. NGS detected the following somatic mutations: Case #2 DNMT3A p.R882H c.2645G>A; Case #3 JAK2 V617F. Case #1 had multiple relapses of BCC, but a subsequent marrow biopsy did not identify any involvement by mastocytosis. Case #2 had mast cell leukemia, which typically has a poor prognosis; however, this patient has survived for several years. Case #3 had essential thrombocythemia and systemic mastocytosis with an associated hematological neoplasm, and her symptoms were stable. Treatment modalities for the three patients ranged from surgical excision to anti-mastocytosis therapy, with favorable outcomes (Table 1). Conclusion The coexistence of BCC with mastocytosis poses diagnostic challenges due to its infrequency and varied clinical presentations. Previous literature reports on treatments of mastocytosis such as phototherapy and steroids, which have been identified as risk factors for the development of basal cell carcinoma. However, recognizing this unique combination in clinical practice may aid in providing appropriate treatment strategies, ultimately leading to favorable patient outcomes.

Clinicopathologic features and new factors affecting constitution of eyelid neoplasms: a 10-year multicentre experience in southern coastal China

ObjectiveThis study aims to delineate the key characteristics of eyelid neoplasms in central and southern coastal China and to explore potential factors affecting tumour development. MethodsThis was a retrospective, multicentre observational study. In total, 1302 cases of eyelid neoplasms diagnosed in 2 tertiary hospitals were reviewed from January 2013 to May 2023. Histogenesis, pathologic diagnosis, and potential risk factors were investigated, and the findings were compared with data from various regions and countries. Age- and sex-specific incidence rates, time trends, distributions across age groups, and the relationship with the Sociodemographic Index, latitude, and altitude were calculated. ResultsThere were 1162 benign (89.2%) and 140 malignant (10.8%) cases, representing 63 pathologic types. The median age of benign cases (50 years) was significantly lower than that of malignant cases (72 years) (P < 0.05). The most common benign and malignant lesions were intradermal nevus (28.83%) and basal cell carcinoma (BCC) (74.29%). A relatively younger median age (68 years) for sebaceous gland carcinoma (SGC) was observed, with a male preponderance (sex ratio 2:1). Analyses of the proportions of BCC, SGC, and squamous cell carcinoma in eyelid malignancies revealed significant regression equations (P < 0.05). ConclusionsMost eyelid neoplasms are of epithelial and melanocytic origin, with benign tumours being predominant. The regions with greater Sociodemographic Index exhibit a greater incidence of BCC and a lower incidence of squamous cell carcinoma and SGC. BCC appears to have a greater incidence in regions located at higher latitudes.

Impact of Sunscreen on Preventing Each Type of Facial Skin Cancer

The most frequent cancer in the US is skin cancer, around 5.4 million cases of Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC) are treated every year, while BCC is more common. Exposure to ultraviolet rays is the source of four varieties of skin cancer: BCC, SCC, Melanoma, and Merkel Cell Carcinoma (MCC). Since there are several experiments done on the influence of sunscreen on skin cancer, this paper aims to offer a comprehensive and symmetric conclusion to existing research. This paper summarizes the current studies finished for each type of skin cancer that might be caused by high levels of UV exposure. This study cites 4 experiments for melanoma, and three of them show a reduction in the rate of melanoma if sun blockers were used. This paper also uses three research for SCC and BCC to analyze the relationship between sun cream application and the probability of having SCC and BCC. None of them found that sunscreen will decrease the rate of SCC and one of them contends that sun lotion can prevent some of SCC. There is no current research about MCC, as the difficulty of holding this kind of experiment. This study will provide a reference for the medical field and the general public to analyze if sun lotion should be employed to prevent skin cancers.

'Pitfalls for differentiating basal cell carcinoma from non-basal cell carcinoma on optical coherence tomography: A clinical series'.

Optical coherence tomography (OCT), a non-invasive diagnostic modality, may replace biopsy for diagnosing basal cell carcinoma (BCC) if a high-confidence BCC diagnosis can be established. In other cases, biopsy remains necessary to establish a histopathological diagnosis and treatment regimen. It is, therefore, essential that OCT assessors have a high specificity for differentiating BCC from non-BCC lesions. To establish high-confidence BCC diagnoses, specific morphological BCC characteristics on OCT are used. This study aimed to review several cases of non-BCC lesions that were misclassified as BCC by experienced OCT assessors, thereby providing insight into the causes of these misclassifications and how they may be prevented. The study population consisted of patients who had a histopathologically-verified non-BCC lesion. Patients from Maastricht University Medical Center+ from February 2021 to April 2021 were included in the study. Two independent OCT assessors assessed OCT scans. One OCT assessor recorded the presence or absence of validated morphological BCC characteristics. A false-positive OCT test result was defined as certainty of BCC presence in a non-BCC lesion. The frequency of misclassifications and the presence or absence of morphological BCC features are discussed. A total of 124 patients with non-BCC lesions were included. Six patients were misclassified by both OCT assessors and are discussed in more detail. Histopathological diagnoses were squamous cell carcinoma (n = 2/21), actinic keratosis (n = 2/29), squamous cell carcinoma insitu/Bowen's disease (n = 1/16), or interphase dermatitis (n = 1/4). In all misclassified cases, multiple, apparent morphological BCC characteristics on OCT were present. Most non-BCC lesions are recognized as such by OCT assessors. However, there remains a small risk that a high-confidence BCC diagnosis is established in non-BCC lesions wherein features mimicking validated BCC characteristics are present. Misclassification may be prevented by careful delineation of epidermal layers and good differentiation between dermal ovoid structures typical of BCC versus squamous cell carcinoma.

SpotCheck: A skin cancer diagnostic clinical trial comparing dermoscopy-enhanced telemedicine to in-person evaluation.

1604 Background: Low socioeconomic status and long distances to a diagnosing provider are factors associated with poor melanoma outcomes, including advanced stage at presentation. Telemedicine offers improved access to diagnostic services for patients in medically underserved communities. Dermoscopy is an established skin imaging method with greater diagnostic accuracy for skin cancers compared to naked eye examination alone. We evaluated the safety and efficacy of a dermoscopy-enhanced, store-and-forward telemedicine-based skin cancer diagnostic platform in a prospective clinical trial. Methods: Participants were recruited primarily through advertisements in local newspapers. Subjects with self-identified skin lesions concerning for malignancy could have up to three lesions evaluated. Clinical and dermoscopic images of each lesion were captured, and were stored-and-forwarded to a team of three dermatologists (TeleTeam) working remotely, and independently. Participants were also evaluated face-to-face by a dermatologist (F2F). Participants were offered biopsies by the F2F (if needed) at the time of the visit, or at a follow up visit if the biopsy was only recommended by one or more members of the TeleTeam. The TeleTeam was blinded to the F2F recommendations. Results: We enrolled 146 subjects with 375 lesions of concern for skin cancer between September 2020 and December 2022. Baseline characteristics: 94 (64%) female; median age 65 years (range: 25-90 years); 92 (63%) non-Hispanic White; 22 (15%) Black; 11 (7%) Hispanic White; 8 (6%) Asian; 13 (9%) other or preferred not to say. Nineteen participants (13%) had a prior skin cancer including 2 with melanoma (one also with basal cell carcinoma (BCC)), and 17 with keratinocyte cancers (BCC and/or squamous cell carcinoma (SCC)). Overall, 363/375 (97%) skin lesions were clinically or histopathologically benign; 14/146 (10%) patients had a malignant or atypical skin growth. These included 12 skin cancers: 1 stage IA melanoma (0.5mm in thickness); 1 in-situ melanoma; 8 BCC; 2 in-situ SCC; and 2 moderately or severely atypical nevi. F2F recommended biopsy for both melanomas, 7 BCC and 1 SCC. TeleTeam recommended biopsy for both melanomas, 7 BCC, 2 SCC, and both moderately or severely atypical nevi. F2F identified 10/14 malignant or atypical skin growths; the TeleTeam identified 13/14. The benign:malignant ratio of the F2F and TeleTeam recommended biopsies were 2.7:1 and 5.8:1, respectively. The TeleTeam benign:malignant ratio decreased to 4.5:1 after the first 35 subjects were evaluated. Conclusions: Dermoscopy-enhanced teledermatology evaluation appears to be a safe and effective method to triage skin lesions for in-person medical evaluation and biopsy to diagnose skin cancer. Deployment of this diagnostic modality may help reduce melanoma health disparities arising in communities lacking dermatologists. Clinical trial information: NCT04411810 .

Deep learning-based semantic segmentation of non-melanocytic skin tumors in whole-slide histopathological images.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common skin cancer and impose a huge medical burden on society. Histopathological examination based on whole-slide images (WSIs) remains to be the confirmatory diagnostic method for skin tumors. Accurate segmentation of tumor tissue in WSIs by deep-learning (DL) models can reduce the workload of pathologists and help surgeons ensure the complete removal of tumors. To accurately segment the tumor areas in WSIs of BCC, SCC and squamous cell papilloma (SCP, homologous to SCC) with robust models. We established a data set (ZJU-NMSC) containing 151 WSIs of BCC, SCC and SCP in total. Seven models were utilized to segment WSIs, including the state-of-the-art model, models proposed by us and other models. Dice score, intersection over union, accuracy, sensitivity and specificity were used to evaluate and compare the performance of different models. Heatmaps and tumor tissue masks were generated to reflect the results of the segmentation. The processing times of models are also recorded and compared. While the dice score of most models is higher than 0.85, deeplab v3+ has the best performance and the corresponding tumor tissue mask is more consistent with the ground truth tumor areas even with complex and small lobular lesions. This study broadens the use of DL-based segmentation models in WSIs of skin tumors in terms of tumor types and computational approaches. Segmenting tumor areas can simplify the process of histopathological inspection and benefit the diagnosis and following management of the diseases in practice.

A Rare Case of Neglected Giant Basal Cell Carcinoma in a Nurse-Case Report and Literature Review.

Basal cell carcinoma (BCC) is the most common skin cancer in the fair-skinned adult population over 50 years of age and the incidence is rising. Generally, BCC has an indolent course, low mortality and a good prognosis due to low rates of metastasis. Giant basal cell carcinoma is a rare reported oncological entity which accounts for 0.5% to 1% of all cases of BCC and has a diameter larger than 5cm. Basosquamous carcinoma is a rare high-risk type of BCC with clinical and histopathological features of both BCC and squamous cell carcinoma. A 61-year-old female presented to our clinic for a giant bleeding tumor located under her left breast. She initially noted the tumor almost 15 years ago. Although the patient was a nurse, she was afraid to seek medical advice until an episode of significant bleeding. At presentation the tumor was a 15/7cm in size, was invading the underlying structures and had a central ulceration. The margins of the tumoral plaque had several nodules and pearly structures suggesting the possible clinical diagnosis of BCC.

Documented and projected actions in vitro of thyroid hormone as L -thyroxine (T4) on basal cell carcinoma of the skin

Thyroid hormone as L-thyroxine (T4) at physiological concentrations acts at its cell surface receptor on integrin avb3 to stimulate cancer cell proliferation1. These proliferation studies have been conducted in vitro, but pharmacological reduction of T4 and substitution of nuclear receptor ligand 3,3’,5-triiodo-L-thyronine (T3) is a state of euthyroid hypothyroxinemia that has been shown clinically to arrest tumor growth in patients with cancer. T3 is inactive at physiological levels at the plasma membrane integrin receptor. A preclinical study of human basal cell carcinoma (BCC) cells has shown that the integrin thyroid hormone receptor regulates BCC radiosensitivity. While the large majority of BCCs are very manageable clinically, a small number of such tumors are aggressive. In this review of documented and proposed effects of T4 on BCC cells, we raise the possibility that BCC aggressiveness reflects T4 actions on its thyrointegrin target. The functions affected by T4 at the integrin in other human cancers include enhanced cell proliferation, anti-apoptosis, immune checkpoint regulation and metastasis, as well as state of radiosensitivity. The importance of investigating this possible pathophysiology is that euthyroid hypothyroxinemia may be tested as a treatment option.

468 Preferentially Expressed Antigen in Melanoma Modulates Sensitivity to Retinoic Acid and Cell Cycle Control in Immortalized and Malignant Keratinocytes

Retinoids can be used to treat and prevent the formation of basal cell carcinoma (BCC) and squamous cell carcinomas (SCCs; notably cutaneous and oral SCC). Preferentially Expressed Antigen in Melanoma (PRAME), a gamete-specific repressor of retinoid-induced differentiation, is ectopically expressed in BCC and SCC tumors. However, the effects of PRAME on the development of these cancers and their sensitivity to retinoid therapies are unknown. The purpose of this study was to investigate PRAME’s influence on retinoid response and proliferation in benign human keratinocytes, BCC and SCC cells.

Gold nanorods-loaded hydrogel-forming needles for local hyperthermia applications: Proof of concept

Basal cell carcinoma (BCC) is the most common form of skin cancer and responsible for most of the cancer related morbidities and pose a significant public health concern worldwide. Surgery treatment modality is able to clear the BCC, yet it mostly leads to scar formation. Plasmonic photothermal therapy (PPTT) which involves using gold nanostructures and near-infrared (NIR) light to kill the BCC cells by local heating is associated with excellent tissue preservation and healing without scarring. Parenteral administration of such gold nanostructures suffers from off-target delivery and side effects. Delivering such phototherapeutics directly to the BCC proved to be an attractive alternative route of administration yet encountered with penetration limitations due to the stratum corneum (SC) fierce barrier. In the current study, we developed and optimised a novel NIR light-responsive hydrogel-forming long needle (HFLN) loaded with Gold nanorods (GNRs) as a potential plasmonic photothermal device for localised treatment of nodular BCC. The HFLN was prepared from Gantrez® S-97 and poly(ethylene glycol) (PEG) 200 Da and characterized in terms of swelling, insertion and mechanical properties. GNRs were synthesised and tunned using seed-mediated growth method. The integrated devices developed could revolutionise BCC treatment benefiting both patients and healthcare providers.

In vitro 5-Fluorouracil resistance produces enhanced photodynamic therapy damage in SCC and tumor resistance in BCC.

Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, with rising incidence in the recent years. It includes basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Several non-invasive therapies have been developed for its treatment such as topical 5-Fluorouracil (5FU) and photodynamic therapy (PDT), among others. Despite both are appropriated for NMSC treatment, recurrence cases have been reported. To prevent this, in this work we explore the potential of the combination of PDT and 5FU to treat SCC and BCC. First we evaluate the efficacy of PDT in cells resistant to 5FU. For this purpose, we use SCC-13 and CSZ-1 cells, obtained from a human SCC and a murine BCC, respectively. We first induced 5FU resistance in these cell lines by repeated treatments with the drug and then, the efficacy to PDT was evaluated. The results obtained indicated that SCC-5FU resistant cells were sensible to PDT administration, whereas BCC-5FU resistant cells were also resistant to PDT. The observed responses in both cell lines are in concordance to Protoporphyrin IX (PpIX) and reactive oxygen species (ROS) levels produced after the incubation with MAL and subsequent light exposure. The obtained data support the fact that PDT seems to be an appropriate therapeutic option to be administered after 5FU resistance in SCC. However, PDT would not be a choice therapy for resistant BCC cells to 5FU.

847 Modeling basal cell carcinoma in 3D organotypic raft cultures

Basal cell carcinoma (BCC) is the most-commonly diagnosed cancer worldwide with limited availability for non-surgical treatments. The Hedgehog signaling cascade drives tumorigenesis, but efforts to develop effective chemotherapeutics have been thwarted by chemoresistant tumor recurrence. A contributing factor to this is an overall lack of human-based preclinical models. We endeavored to develop 3D organotypic raft models that mimic characteristics of human BCC by combining primary normal human epidermal keratinocytes (NHEK) with established murine BCC cells.

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment.

How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity–PAGA, cellular entropy, and regulon analysis in stromal cells reveals a cancer-specific rewiring of fibroblasts, where STAT1, TGF-β, and inflammatory signals induce a noncanonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, whose expression we validated in situ. Last, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro vismodegib-resistant BCC cell growth, Hedgehog signaling, and in vivo tumor growth in a BCC mouse model, validating HSP70’s essential role in tumor growth and reinforcing the critical nature of tumor microenvironment cross-talk in BCC progression.

Long-Noncoding RNA ANCR Activates the Hedgehog Signaling Pathway to Promote Basal Cell Carcinoma Progression by Binding to PTCH.

PurposeThe long non-coding RNA (lncRNA) anti-differentiation noncoding RNA (ANCR) is closely related to the occurrence and development of various malignancies. However, its expression and potential role in basal cell carcinoma (BCC) have not been established. In this study, we characterized the effects of ANCR in BCC and its underlying mechanism.MethodsThe expression of ANCR in BCC tissues and cells was detected by qRT-PCR. Proliferation, invasion, migration and apoptosis of ANCR overexpressed or knock down TE354.T and A431 cells were examined by CCK8, transwell assay, wound healing assay and flow cytometry analysis, respectively. Western blot was performed to measure the expression of apoptosis-related proteins (BAX, BCL2 and Cleaved-caspase3), epithelial-mesenchymal transformation-related proteins (E-cadherin, N-cadherin, vimentin and β-catenin), and Hedgehog-pathway-related proteins (PTCH, GLI1 and SMO). RNA pull-down assay was used to analyze the relationship between ANCR and PTCH. The effect of ANCR on BCC growth in vivo was analyzed using xenograft model. TUNEL assay was used to determine the cell apoptosis.ResultsANCR and Hedgehog pathway were more highly expressed in BCC tissues than in adjacent normal tissues. ANCR overexpression substantially promoted BCC cell proliferation, invasion, and migration, inhibited apoptosis, and up-regulated BCL2 and decreased the expression of BAX and Cleaved-caspase3 proteins. Additionally, the upregulation of N-cadherin, vimentin, β-catenin, PTCH, GLI1, and SMO expression, and downregulation of E-cadherin expression were observed after ANCR overexpression. Moreover, ANCR knockdown had the opposite effects. An RNA pull-down assay further revealed that ANCR is specifically bound to PTCH. In vivo experiments also showed that ANCR overexpression significantly increased tumor growth and decreased apoptosis, which was reversed by cyclopamine, a specific inhibitor of the Hedgehog signaling pathway.ConclusionANCR activates the Hedgehog signaling pathway by binding to PTCH, thereby promoting BCC progression; accordingly, ANCR could be a candidate therapeutic target in BCC.

Delivery of Targeted Co(III)-DNA Inhibitors of Gli Proteins to Disrupt Hedgehog Signaling.

The Hedgehog (Hh) signaling pathway is integral for embryonic development and normal cell maintenance. However, aberrant expression of the Hh pathway is recognized as the oncogenic driving force for basal cell carcinoma (BCC). Current chemotherapeutic treatments that inhibit Hh signaling allow treatment of only locally advanced and metastatic BCCs via inhibition of the transmembrane protein, smoothened. It is further recognized that downstream mutations often lead to chemoresistant tumor recurrence. The Gli proteins are the ultimate regulators of Hh signaling and belong to a family of Cys2His2 zinc finger transcription factors (ZnFTFs) that we have shown can be irreversibly inhibited by a series of cobalt(III) Schiff base-DNA (CoSB-DNA) conjugates. However, a significant challenge is the delivery of CoSB-DNA complexes in mammalian tissues. Herein, we report a polyethyleneimine-functionalized graphene oxide nanoconjugate (GOPEI) that delivers CoGli, a CoSB-DNA complex that targets Gli specifically. We describe the characterization of the surface functionalization of GOPEI and accumulation in ASZ murine BCC cells via confocal microscopy and inductively coupled plasma-mass spectrometry (ICP-MS). Lysosomal escape of CoGli is further confirmed by confocal microscopy. We report the successful targeting of Gli by CoGli and a 17-fold improvement in potency over small-molecule Gli inhibitor GANT-61 in inhibiting Hh-driven migration of ASZ murine BCC cells. This study provides a promising starting point for further investigating CoGli inhibitors of Hh signaling in developed mammalian tissues.

Increased expression of LAT1 in basal cell carcinoma: implications for tumour cell survival.

Basal cell carcinoma (BCC) is the most common type of cancer in fair-skinned individuals worldwide. Altered metabolism is a hallmark of cancer, and a growing body of evidence has shown increased expression of the large neutral amino acid transporter small subunit 1 (LAT1) in several types of cancers, including BCC. However, the mechanisms behind changed LAT1 expression in BCC are largely unknown. To describe the protein expression of LAT1 and its colocalization with LAT2, and to examine LAT1 in association with BCC tumour biology characteristics such as cell proliferation, apoptosis and hypoxia. Immunofluorescence stains were used on formalin-fixed, paraffin-embedded tissue samples (n = 14) from excised BCCs, and their protein-staining patterns were examined. There was no correlation between expression of LAT1 and LAT2, and the colocalization was low. Compared with normal epidermis, there was significantly higher expression in BCC tissue of the proliferation markers topoisomerase IIα (P < 0.01) and Ki-67 (P = 0.01). The fraction of LAT1-expressing cells in BCC tissue was significantly (P < 0.01) inversely correlated with the fraction of proliferative active tumour cells. Cleaved caspase-3 was significantly (P = 0.02) increased in tumour areas with high LAT1 expression. The present study shows that LAT1 is not usually expressed by proliferating BCC cells. The morphological localization suggests that tumour cells use LAT1 to adapt to environmental changes such as starvation and/or hypoxia. These findings could have implications for future development of LAT1-inhibitory BCC treatments.

PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation.

Basal cell carcinoma (BCC) is a locally invasive epithelial cancer that is primarily driven by the Hedgehog (HH) pathway. Advanced BCCs are a critical subset of BCCs that frequently acquire resistance to Smoothened (SMO) inhibitors and identifying pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify a PI3K pathway expression signature in BCC. Pharmacological inhibition of PI3K activity in BCC cells significantly reduces cell proliferation and HH signaling. However, treatment of Ptch1fl/fl; Gli1-CreERT2 mouse BCCs with the PI3K inhibitor BKM120 results in a reduction of tumor cell growth with no significant effect on HH signaling. Downstream PI3K components aPKC and Akt1 showed a reduction in active protein, whereas their substrate, cyclin-dependent kinase inhibitor p21, showed a concomitant increase in protein stability. Our results suggest that PI3K promotes BCC tumor growth by kinase-induced p21 degradation without altering HH signaling.

Association between income and suspected nonmelanoma and melanoma skin cancers among participants of the American Academy of Dermatology's SPOT Skin Cancer screening program: A cross-sectional analysis

To the Editor: Lower income and socioeconomic status (SES) have been associated with a worse prognosis of cutaneous melanoma, partly due to poorer skin cancer awareness and screening, resulting in thicker tumors at diagnosis.1 Meanwhile, higher SES populations in selected European countries (Denmark, the Netherlands, Italy) have a greater incidence of nonmelanoma skin cancer, particularly basal cell carcinoma (BCC). However, no association between SES and survival has been found.2,3 While prior research focused on the American Academy of Dermatology's SPOT skin cancer screening program reported risk factors for suspected melanoma, BCC, and squamous cell carcinoma (SCC),4 income as a proxy for SES has not been studied as an independent predictor of skin cancer risk among this population.

HLA-G, cytokines, and cytokine receptors in the non-aggressive basal cell carcinoma microenvironment.

Non-aggressive basal cell carcinoma (BCC) growth is slow and might be mediated by the immune system. This study analysed the human leukocyte antigen (HLA)-G expression and cytokine profile in non-aggressive BCC subtypes from distinct locations. HLA-G was evaluated via immunohistochemistry and cytokine expression was analysed by a quantitative real-time polymerase chain reaction in 26 primary BCC samples, including nodular BCC (nBCC, n = 16) and superficial BCC (n = 10) from cephalic (ceBCC, n = 12) and non-cephalic (n = 14) locations, and by bioinformatics analysis of public GEO databases. Inflammatory infiltrate was concentrated around the tumour nests. HLA-G-positive inflammatory cells (53.85%) were more abundant than HLA-G-positive tumour cells (21.54%, p < 0.001). HLA-G immunoreactivity was predominantly cytoplasmic in BCC cells and was primarily associated with lymphocytes and macrophages surrounding the tumour. nBCC showed a higher percentage of HLA-G-positive tumour cells (p = 0.04), and ceBCC showed stronger intensity (p = 0.04). IFN-gamma and IL-10 expression were 1.95 and 1.22-fold higher, respectively, relative to that in normal skin, with a positive correlation between them (r = 0.61; p = 0.002). IL-23 expression was higher in nBCC (p = 0.04) and positively correlated (r = 0.47; p = 0.05) with slight intensity of HLA-G-positive tumour cells. The up-regulation of IL23A and IL10RB and down-regulation of IFNGR1 and IL4R gene expression in BCC compared to levels in adjacent tissues were demonstrated in the GSE125285 dataset. The exhibited cytokine profile was consistent with the induction of HLA-G expression in non-aggressive BCC subtypes. HLA-G expression in tumour cells and inflammatory cells surrounding BCCs supports the generation of inhibitory signals on various immune cells that exert anti-tumour responses.

Evaluation of The Best Surgical Margin for Basal Cell Carcinoma

Background: Basal cell carcinoma (BCC) is one of the non-melanocytic malignancies of the skin, originating from the epidermal basal cells. It is considered the most common skin malignancy in humans. The treatment should remove the lesion with preserving the maximum level of healthy surrounding tissues. So, treatment is controversial between adequate safety margin and leaving satisfactory cosmetic results. Objective: In this study, we aim to evaluate the intact safety margin for BCC post-operative, being regarded as 3 mm or more before surgery (pathologically by routine and immunohistochemical staining using BerEP4). Patients and Methods: The study included 40 patients presented with basal cell carcinoma (BCC). All were assessed for the duration, size, type, and site of the lesion. The treatment of the primary lesion and recurrence time was reported for all cases. Different reconstructive types of local fascio-cutaneous flaps were performed. The excised specimens were referred to pathological verification of the diagnosis and evaluation of the boundaries, either free or infiltrated. Results: There was a statistically significant association between recurrence and tumor size (p=0.001), deep facial invasion (p < 0.001), muscle invasion (p=0.001), ill-defined tumor borders (p < 0.001), positive surgical margins, and safety margins size (p < 0.001). Conclusion: Excision of BCC with 3 mm or more as a safety margin is enough to preserve healthy tissues and avoid the requirement for difficult procedures of reconstruction. The use of BerEP4 is a highly specific marker for detecting BCC cells that, can be missed by routine H&E staining.