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Modern Pathology : An Official Journal... Jul 2014Although the cure rate for cutaneous squamous cell carcinoma is high, the diverse spectrum of squamous cell carcinoma has made it difficult for early diagnosis,...
Although the cure rate for cutaneous squamous cell carcinoma is high, the diverse spectrum of squamous cell carcinoma has made it difficult for early diagnosis, particularly the aggressive tumors that are highly associated with mortality. Therefore, molecular markers are needed as an adjunct to current staging methods for diagnosing high-risk lesions, and stratifying those patients with aggressive tumors. To identify such biomarkers, we have examined a comprehensive set of 200 histologically defined squamous cell carcinoma and normal skin samples by using a combination of microarray, QRT-PCR and immunohistochemistry analyses. A characteristic and distinguishable profile including matrix metalloproteinase (MMP) as well as other degradome components was differentially expressed in squamous cell carcinoma compared with normal skin samples. The expression levels of some of these genes including matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 10 (MMP10), parathyroid hormone-like hormone (PTHLH), cyclin-dependent kinase inhibitor 2A (CDKN2A), A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), FBJ osteosarcoma oncogene (FOS), interleukin 6 (IL6) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) were significantly differentially expressed (P≤0.02) in squamous cell carcinoma compared with normal skin. Furthermore, based on receiver operating characteristic analyses, the mRNA and protein levels of MMP1 are significantly higher in aggressive tumors compared with non-aggressive tumors. Given that MMPs represent the most prominent family of proteinases associated with tumorigenesis, we believe that they may have an important role in modulating the tumor microenvironment of squamous cell carcinoma.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Gene Expression Regulation, Neoplastic; Humans; Skin; Skin Neoplasms; Tissue Array Analysis
PubMed: 24356192
DOI: 10.1038/modpathol.2013.217 -
Annual International Conference of the... 2014The double Debye model can be used to capture the dielectric response of human skin in terahertz regime due to high water content in the tissue. The increased water...
The double Debye model can be used to capture the dielectric response of human skin in terahertz regime due to high water content in the tissue. The increased water proportion is widely considered as a biomarker of carcinogenesis, which gives rise of using this model in skin cancer detection. Therefore, the goal of this paper is to provide a specific analysis of the double Debye parameters in terms of non-melanoma skin cancer classification. Pearson correlation is applied to investigate the sensitivity of these parameters and their combinations to the variation in tumor percentage of skin samples. The most sensitive parameters are then assessed by using the receiver operating characteristic (ROC) plot to confirm their potential of classifying tumor from normal skin. Our positive outcomes support further steps to clinical application of terahertz imaging in skin cancer delineation.
Topics: Biomarkers, Tumor; Carcinoma, Basal Cell; Humans; Models, Theoretical; ROC Curve; Skin; Skin Neoplasms; Terahertz Spectroscopy
PubMed: 25570059
DOI: 10.1109/EMBC.2014.6943691 -
Journal of the European Academy of... Jan 2023
Topics: Humans; Carcinoma, Squamous Cell; Keratoacanthoma; Skin; Skin Diseases; Skin Neoplasms
PubMed: 35993817
DOI: 10.1111/jdv.18559 -
The Journal of Investigative Dermatology Feb 2019
Randomized Controlled Trial
Topics: Carcinogenesis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Count; Humans; Incidence; Macrophages; Niacinamide; Skin; Skin Neoplasms
PubMed: 30244097
DOI: 10.1016/j.jid.2018.08.018 -
Journal of Cutaneous Pathology Mar 2009Proteinase-activated receptor-2 (PAR-2) is a transmembrane G-protein expressed in many normal tissues and overexpressed in several cancer cell lines. It contributes to... (Comparative Study)
Comparative Study
Proteinase-activated receptor-2 (PAR-2) is a transmembrane G-protein expressed in many normal tissues and overexpressed in several cancer cell lines. It contributes to metastasis, promotes epidermal growth factor receptor proliferation, angiogenesis and tumor progression in many carcinomas. The purpose of this study was to investigate the expression of PAR-2 in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in comparison with that of normal skin. Immunohistochemical (IHC) expression of PAR-2 was examined using paraffin-embedded sections from 30 BCCs, 30 SCCs and also 30 normal sun-exposed skin specimens. PAR-2 was expressed in all specimens of SCC and normal skin. In marked contrast, all BCC specimens had negative IHC staining. Given the important role of PAR-2 in angiogenesis and metastasis, our finding can explain the far less aggressive behavior of BCC as compared with SCC.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Male; Middle Aged; Receptor, PAR-2; Skin; Skin Neoplasms
PubMed: 19032384
DOI: 10.1111/j.1600-0560.2008.01018.x -
Biochemical and Biophysical Research... Jul 1998We surveyed expression of Hox genes in multiple carcinogenesis of mouse skin by RT-PCR cloning. According to the sequences of the amplified DNA fragments within the...
We surveyed expression of Hox genes in multiple carcinogenesis of mouse skin by RT-PCR cloning. According to the sequences of the amplified DNA fragments within the homeobox of Hox genes, 25 of the 39 known Hox genes were amplified in the normal dorsal skin of adult mice. In the papilloma and carcinoma, clones of Hox A7 and Hox B7 were preferentially isolated among others. The entire Hox D locus was silent in both papilloma and carcinoma. Our present results suggest that the majority of Hox gene family members are expressed in normal mouse skin, while the repertoire is substantially limited in the papilloma and carcinoma.
Topics: Animals; Carcinoma; Female; Gene Amplification; Genes, Homeobox; Homeodomain Proteins; Mice; Mice, Inbred ICR; Papilloma; Polymerase Chain Reaction; Reference Values; Skin; Skin Neoplasms
PubMed: 9703999
DOI: 10.1006/bbrc.1998.9076 -
JAMA Dermatology Jan 2020Detection of cutaneous cancer on the face using deep-learning algorithms has been challenging because various anatomic structures create curves and shades that confuse...
IMPORTANCE
Detection of cutaneous cancer on the face using deep-learning algorithms has been challenging because various anatomic structures create curves and shades that confuse the algorithm and can potentially lead to false-positive results.
OBJECTIVE
To evaluate whether an algorithm can automatically locate suspected areas and predict the probability of a lesion being malignant.
DESIGN, SETTING, AND PARTICIPANTS
Region-based convolutional neural network technology was used to create 924 538 possible lesions by extracting nodular benign lesions from 182 348 clinical photographs. After manually or automatically annotating these possible lesions based on image findings, convolutional neural networks were trained with 1 106 886 image crops to locate and diagnose cancer. Validation data sets (2844 images from 673 patients; mean [SD] age, 58.2 [19.9] years; 308 men [45.8%]; 185 patients with malignant tumors, 305 with benign tumors, and 183 free of tumor) were obtained from 3 hospitals between January 1, 2010, and September 30, 2018.
MAIN OUTCOMES AND MEASURES
The area under the receiver operating characteristic curve, F1 score (mean of precision and recall; range, 0.000-1.000), and Youden index score (sensitivity + specificity -1; 0%-100%) were used to compare the performance of the algorithm with that of the participants.
RESULTS
The algorithm analyzed a mean (SD) of 4.2 (2.4) photographs per patient and reported the malignancy score according to the highest malignancy output. The area under the receiver operating characteristic curve for the validation data set (673 patients) was 0.910. At a high-sensitivity cutoff threshold, the sensitivity and specificity of the model with the 673 patients were 76.8% and 90.6%, respectively. With the test partition (325 images; 80 patients), the performance of the algorithm was compared with the performance of 13 board-certified dermatologists, 34 dermatology residents, 20 nondermatologic physicians, and 52 members of the general public with no medical background. When the disease screening performance was evaluated at high sensitivity areas using the F1 score and Youden index score, the algorithm showed a higher F1 score (0.831 vs 0.653 [0.126], P < .001) and Youden index score (0.675 vs 0.417 [0.124], P < .001) than that of nondermatologic physicians. The accuracy of the algorithm was comparable with that of dermatologists (F1 score, 0.831 vs 0.835 [0.040]; Youden index score, 0.675 vs 0.671 [0.100]).
CONCLUSIONS AND RELEVANCE
The results of the study suggest that the algorithm could localize and diagnose skin cancer without preselection of suspicious lesions by dermatologists.
Topics: Adult; Aged; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Datasets as Topic; Face; Female; Humans; Image Processing, Computer-Assisted; Keratinocytes; Male; Middle Aged; Neural Networks, Computer; Photography; ROC Curve; Skin; Skin Neoplasms
PubMed: 31799995
DOI: 10.1001/jamadermatol.2019.3807 -
Zentralblatt Fur Allgemeine Pathologie... 1984Two cases of neuroendocrine carcinomas of the skin were examined by light microscopic and electron microscopic methods. In both patients the disease showed an unusual...
Two cases of neuroendocrine carcinomas of the skin were examined by light microscopic and electron microscopic methods. In both patients the disease showed an unusual course characterized by the occurrence of numerous and wide-spread skin nodules. Light microscopically, we found a uniform tumor tissue with trabecular, nest- or cord-like arrangement of cancer cells. At electron microscopic investigation, neurosecretory granules (dense-cored vesicles) were detected. These organelles had a diameter between 90 and 220 nm. Furthermore, small bundles of intermediate filaments and a well-developed Golgi system as well as numerous vesicular structures were recognized. Specialized cell junctions were lacking, tumor cell complexes were often enveloped by a basal lamina-like structure. The light microscopic and electron microscopic observations are in accordance with other reports. The relationship of neuroendocrine skin carcinomas to Merkel cells is discussed. However, we suggest an origin of these carcinomas from multipotent epithelial stem cells. The multicentric development in our cases, the tumor localization, and recent electron microscopic findings in basal cell carcinomas lend the basis for speculations on relations between neuroendocrine carcinomas and basal cell carcinomas of the skin. Lastly, the morphologic differential diagnosis of neuroendocrine carcinomas is presented. Special attention is called to the distinction from melanomas, lymphomas and other neuroendocrine tumors. In spite of the fact that neuroendocrine carcinomas of the skin are well defined and considered to be a clinico-pathologic entity there are some open questions concerning the tumor biology and histogenesis.
Topics: Adenocarcinoma; Aged; Carcinoma, Basal Cell; Cytoplasmic Granules; Diagnosis, Differential; Humans; Male; Microscopy, Electron; Middle Aged; Skin; Skin Neoplasms
PubMed: 6524125
DOI: No ID Found -
Modern Pathology : An Official Journal... Nov 2002There are approximately 200,000 new cases of cutaneous squamous cell carcinoma diagnosed each year in the United States, with between 1300 and 2300 deaths per year from... (Comparative Study)
Comparative Study
There are approximately 200,000 new cases of cutaneous squamous cell carcinoma diagnosed each year in the United States, with between 1300 and 2300 deaths per year from metastatic disease. The tumor suppressor p16, encoded by the CDKN2/INK4a locus, has been reported mutated in >or=24% of squamous cell carcinomas. Mutations of the p16 gene have also been found in actinic keratoses, the first identifiable lesion in the continuum from normal skin to squamous cell carcinoma. We hypothesized that there may be an appreciable difference in expression of p16 between normal skin, actinic keratoses, squamous cell carcinoma in situ, and invasive squamous cell carcinoma. Ten actinic keratoses, 10 in situ squamous cell carcinomas, and 10 invasive squamous cell carcinomas were examined using the immunoperoxidase method with antigen retrieval for anti-p16(INK4a) antibody. All 10 actinic keratoses were positive for weak to moderate p16 staining in the lower third to lower half of the epidermis (especially the basal keratinocytes). This staining was significant when compared with the lack of staining seen in normal skin controls. Twenty percent of in situ squamous cell carcinomas had moderate to strong staining in only the lower half to lower two thirds of the epidermis, whereas 70% of the in situ squamous cell carcinomas exhibited full-thickness p16 staining, with no staining in the dermis. Thirty percent of invasive squamous cell carcinomas had full-thickness staining of the in situ component of the lesion, and 100% of invasive squamous cell carcinomas exhibited moderate to strong staining of the invasive component of the lesion. These findings indicate correlation between the increased expression of p16 during the progression of skin from actinic keratosis to in situ squamous cell carcinoma to invasive squamous cell carcinoma. These data may lend further support to the view of the actinic keratosis as a precursor lesion to squamous cell carcinoma.
Topics: Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Humans; Immunohistochemistry; Keratosis; Skin; Skin Neoplasms
PubMed: 12429789
DOI: 10.1097/01.MP.0000032536.48264.D1 -
The American Journal of Dermatopathology Aug 1991Five cases of basal cell carcinomas (BCC) of the skin are described showing morphologic and immunohistochemical features of myoepithelial differentiation....
Five cases of basal cell carcinomas (BCC) of the skin are described showing morphologic and immunohistochemical features of myoepithelial differentiation. Histologically, they were characterized by a dermal proliferation of tumor cells connected with the epidermis by areas showing the features of conventional BCC, with the deeper portions of the lesion showing a population of oval to spindle cells with eccentric nuclei and homogeneous, ground-glass, or hyaline eosinophilic cytoplasm characteristic of the so-called hyaline cell of myoepithelial tumors of salivary glands. Additionally, scattered cells showing a signet ring configuration were present, and in two cases, focal areas displaying chondromyxoid elements were also seen that appeared to merge imperceptibly with the surrounding spindle cell population. By immunohistochemistry, the tumor cells in the spindle cell component showed strong, diffuse positivity for CAM 5.2 and muscle specific actin, and variable expression of keratin AE1/AE3, vimentin, glial fibrillary acidic protein, and S-100 protein, these findings being consistent with the immunostaining pattern of myoepithelial cells and their neoplasms. A brief review of the literature on the topic is presented, along with a discussion of the possible pathogenesis of this process.
Topics: Adult; Aged; Antigens, Neoplasm; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Epithelium; Female; Humans; Immunohistochemistry; Male; Middle Aged; Skin; Skin Neoplasms
PubMed: 1928620
DOI: 10.1097/00000372-199108000-00005