The differential expression of EPHB4 and ephrin B2 in cutaneous squamous cell carcinoma according to the grade of tumor differentiation: a clinicopathological study.

BACKGROUND: EPHB4 and its ligand, ephrin B2, which are receptor tyrosine kinases of the erythropoietin-producing hepatocellular (EPH) family, are known to be linked to several human cancers. The aim of this study was to investigate their expression patterns in cutaneous squamous cell carcinoma (CSCC) in association with tumor differentiation and other variable clinical characteristics. MATERIALS AND METHODS: Immunohistochemical staining for EPHB4 and ephrin B2 was performed in 32 cases of CSCC with different histologic grades. The clinical characteristics and histologic grades of CSCC were evaluated in association with EPHB4 and ephrin B2 expression patterns. RESULTS: EPHB4 and ephrin B2 expression levels were significantly inversely proportional to the grade of differentiation of CSCC (P < 0.001 and P < 0.001, respectively). CONCLUSION: These results indicated that EPHB4 and ephrin B2 can be useful markers for poorly differentiated CSCC.

Expression of insulin-like growth factor-1 receptor in conventional cutaneous squamous cell carcinoma with different histological grades of differentiation.

BACKGROUND: Insulin-like growth factor-1 receptor (IGF-1R) is a key regulator of cell transformation and controls the expression of genes that governs cell cycling and cell survival. The aim of this pilot study was to gain insight into the expression pattern of IGF-1R in conventional cutaneous squamous cell carcinoma (CSCC) using immunohistochemical analysis. MATERIALS AND METHODS: Five cases of normal human paraffin-embedded skin sections, 4 cases of actinic keratosis, and 28 cases of paraffin-embedded sections of different histological subtypes of CSCC were selected for immunohistochemical analysis. RESULTS: In normal skin, IGF-1R expression was detected in the epidermal basal cell layer. In actinic keratosis, IGF-1R was expressed in the lower part of the epidermis. IGF-1R was detected in the cell surface membrane of well-differentiated CSCC. In moderately differentiated CSCC, IGF-1R was expressed predominantly in the cytoplasm. Interestingly, IGF-1R was expressed in the nuclei of tumor cells of poorly differentiated CSCC. CONCLUSIONS: The strong and differential expression of IGF-1R in different histological degrees of CSCC indicates a possible role for IGF-insulin receptor in the carcinogenesis and differentiation of this disease and identifies IGF-1R as an interesting target for prevention and treatment of CSCC that deserves further investigation.

Expression of Fas and Fas ligand in primary cutaneous squamous cell carcinoma in association with grade of tumor differentiation.

BACKGROUND: The aim of this study was to evaluate whether Fas (CD95) and Fas ligand (FasL) immunoreactivity in cutaneous squamous cell carcinoma (SCC) are correlated with grade of tumor differentiation. METHODS: A total of 31 cutaneous SCC specimens excised during 1997-2004 were collected from the four branch hospitals of the Catholic University of Korea. A tissue microarray technique was used for immunohistochemical staining. Expression of Fas and FasL was evaluated in correlation with the grade of tumor differentiation. Statistical analysis was performed using Fisher's exact test and exact trend test. RESULTS: Six of 31 SCCs exhibited strong (+++) intensity for Fas immunostaining, and all of these were well differentiated. Five of 31 SCCs exhibited strong (+++) intensity for FasL staining; all of these were moderately or poorly differentiated. CONCLUSIONS: Fas was expressed more strongly in well-differentiated SCCs than in poorly differentiated tumors. FasL was expressed more strongly in moderately and poorly differentiated tumors. These findings indicate that Fas and FasL play important roles in immune surveillance and grade of differentiation in SCC.

Photorejuvenation using long-pulsed alexandrite and long-pulsed neodymium:yttrium-aluminum-garnet lasers: a pilot study of clinical outcome and patients' satisfaction in Koreans.

Long-pulsed 755-nm alexandrite and long-pulsed 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers have been used for photorejuvenation of the face. The aim of this study was to investigate the safety and efficacy of long-pulsed alexandrite and long-pulsed Nd:YAG lasers for photorejuvenation in Korea. One hundred and sixteen Korean patients with photo-aged facial skin were enrolled. Sixty-two patients with facial pigmentation underwent long-pulsed alexandrite laser treatment. Eleven patients that wanted to improve facial pigmentation with minimal pain had quasi-long-pulsed alexandrite laser treatment. Forty three patients had long-pulsed Nd:YAG laser therapy. Outcome assessments included standard photographs and global evaluation by blinded investigators. The self-assessment grade was provided in questionnaires. Forty-four percent of patients reported excellent or good improvement of their pigmentary lesions (>50% improvement) using a long-pulsed alexandrite laser. Of patients who underwent long-pulsed Nd:YAG laser treatment, 36% reported excellent or good improvement in skin tightening, 50% in facial flushing and 45% in pigmentary lesions. We conclude that long-pulsed alexandrite and long-pulsed Nd:YAG lasers are safe and effective for facial photorejuvenation in Koreans.

Interferon-alpha Induced Sarcoidosis with Cutaneous Involvement along the Lines of Venous Drainage.

Sarcoidosis is a systemic inflammatory disease of an unknown origin and it is characterized by the presence of noncaseating epitheloid cell granulomas in multiple organs. Herein we report on a case of cutaneous and pulmonary sarcoidosis that was associated with interferon alpha treatment for hepatitis C. A 39-year-old man, a former intravenous drug user, presented with several erythematous papules on both antecubital areas. The histopathologic finding of a skin biopsy showed noncaseating granuloma. The mediastinal and axillary lymph nodes were enlarged on chest X-ray and computed tomography. To the best of our knowledge, this is the first report of cutaneous and pulmonary sarcoidosis that was associated with interferon treatment in the Korean dermatologic literature.

Lymphomatoid papulosis followed by anaplastic large cell lymphoma in a pediatric patient.

Lymphomatoid papulosis (LyP) is a benign, self-healing, papular eruption that can wax and wane over time. Transformation to T-cell lymphoma has been well documented in 10% to 20% of adults with LyP. However, this transformation rarely occurs in patients younger than 20 years of age. Here, we present the first known pediatric patient in Korea, a 12-year-old boy who developed a subcutaneous nodule on the scrotum 13 months after papulonecrotic lesions of LyP were identified on both lower extremities and face. Histological and immunohistochemical examination of the subcutaneous nodule revealed anaplastic large cell lymphoma (ALCL). A T-cell receptor gene rearrangement analysis demonstrated an identical rearranged pattern in the two specimens, indicating that a common T-cell clone had proliferated over time in both the LyP and ALCL lesions.

Recent trend in the incidence of premalignant and malignant skin lesions in Korea between 1991 and 2006.

We evaluated the recent trend in the incidence of premalignant and malignant skin lesions between 1991 and 2006. Among 571,057 newly registered dermatology out-patients from our 8 affiliated university hospitals, 2,598 were diagnosed with a premalignant (899, 0.16%) or malignant skin lesions (1,699, 0.30%). Of 899 premalignant cases, 71.2% were actinic keratosis (AK), and 24.6% were Bowen's disease. Of 1,699 malignant cases, 46.2% were basal cell carcinoma, followed by squamous cell carcinoma (19.1%) and melanoma (7.1%). This 16-yr survey was divided equally into two time periods to compare the incidence of premalignant and malignant skin lesions at different time settings. Between 1991 and 1998, the incidence of cutaneous premalignancy was 0.10% which doubled during 1999-2006. For cutaneous malignancy, the incidence was 0.25% during 1991-1998 and 0.34% in 1999-2006. Incidence of AK among the new outpatients was 0.07% in 1991-1998 which staggered up to 0.15% in 1999-2006. These findings show an increase of both premalignant and malignant skin lesions, AK in particular in the dermatology outpatient-based incidence.

The disintegrin-metalloproteinases ADAM 10, 12 and 17 are upregulated in invading peripheral tumor cells of basal cell carcinomas.

BACKGROUND: Members of the a disintegrin and metalloproteinase (ADAM) family are expressed in malignant tumors and participate in the pathogenesis of cancer. However, the presence of ADAM 10, 12, 17 and their role in basal cell carcinoma (BCC) have not been described. The purpose of this study was to investigate expression of ADAM 10, 12 and 17 in BCC. METHODS: Expression of ADAM 10, 12 and 17 was analyzed by immunohistochemistry in skin tissues obtained from 25 patients with different types of BCC. RESULTS: Immunoreactivity of ADAM 10, 12 and 17 was increased at the peripheral tumor margin compared with central areas of BCC tumor cell nests. Immunoreactivity of ADAM 10 and 12 was increased in the deep margin of invading tumor cell nests in mixed BCC. Focally increased expression of ADAM 12 was detected in squamous differentiated tumor cells of nodular BCC. In addition, immunoreactivity of ADAM 17 was increased in superficial BCC. CONCLUSIONS: ADAM 10, 12 and 17 showed different expression pattern in BCC histologic subtypes, indicating their different role in the BCC pathogenesis. Overexpression of ADAM 10, 12 and 17 immunoreactivity in deep invasion area of BCC indicates that these three proteases may play an important role in the locally invasive and highly destructive growth behavior of BCC. Additionally, we suggest that ADAM 17 may play an important role in early development of BCC.

Hair-cycle dependent differential expression of ADAM 10 and ADAM 12: An immunohistochemical analysis in human hair follicles in situ.

BACKGROUND: ADAM proteases play important roles in processes of development and differentiation. However, no report has been found in the literature addressing the expression and function of ADAM proteases during hair cycling. RESULTS: Cytoplasmic expression pattern of ADAM 10, 12 was similar between normal epidermis and hair infundibulum. In addition, cytoplasmic expression of ADAM 10 was observed in the hair bulb keratinocytes and fibroblasts of dermal papilla in anagen I-III hair follicles. In contrast, decreased ADAM 10 expression was observed in the hair matrix keratinocytes as compared to the hair bulb keratinocytes in anagen I-III hair follicles. Interestingly, ADAM 10 immunoreactivity was expressed weakly in the lower portion of outer root sheath (ORS) of anagen VI hair follicles, and strong ADAM 10 expression was detected in the ORS of catagen and telogen hair follicles. By contrast, ADAM 12 expression was not detected in the hair bulb keratinocytes of anagen I-III hair follicles. ADAM 12 immunoreactivity firstly appeared in the inner root sheath ( IRS ) of anagen IV-V hair follicles and was down-regulated in the IRS and hair cortex and medulla of catagen hair follicles, Strong ADAM 12 immunoreactivity was observed in the ORS of catagen and telogen hair follicles. MATERIAL AND METHODS: Samples of normal human skin (n = 30) were used. Immunohistochemical analysis was performed using ADAM 10, 12 specific polyclonal antibodies and a sensitive streptavidin-peroxidase technique. CONCLUSION: Our study demonstrates a comparable staining pattern of decreased ADAM 10 immunoreactivity in hair matrix keratinocytes and the basal cell layer of normal epidermis and hair infundibulum. Expression of ADAM 10 in dermal papilla cells may imply a role in the induction and development of anagen hair follicles. In addition, expression of ADAM 10 in the ORS and hair bulb assume the involvment of ADAM 10 in the downward migration of anagen hair follicles. Furthermore ADAM 12 expression in the IRS may indicate a role in the differentiation of anagen hair follicles. Downregulation of ADAM 12 upon the onset of catagen hair stage suggests that ADAM 12 may play an important role of ADAM 12 in the apoptosis of hair follicle keratinocytes. In summary our findings suggest that ADAM 10 and 12 may be of importance for the regulation of hair cycling.

Overexpression of CXCL16 in lesional psoriatic skin.

BACKGROUND: Psoriasis is characterized as an autoimmune disease resulting in an exaggerated innate immune response. The CXC-chemokine ligand 16 (CXCL16) is described to function as an adhesion molecule, a scavenger receptor or as a soluble molecule it acts as a chemoattractant. CXCL16 has been reported to be expressed in a variety of inflammatory diseases. However, no information has been reported in the literature about the expression of CXCL16 in psoriatic skin. PURPOSE: The present study was designed to analyze the expression and localization of CXCL16 in human psoriatic skin tissues. RESULTS: In normal skin, cytpoplasmic expression of CXCL16 was increased in keratinocytes of upper epidermal cell layers as compared to the lower epidermal cell layers. In lesional psoriatic skin, CXCL16 immunoreactivity was increased in the cytoplasm of keratinocytes of lower epidermal layer kerartinocytes as compared to the normal epidermis. Cytoplasmic CXCL16 expression was increased in the capillary endothelial cells of psoriatic dermis as compared to capillary endothelial cells of the normal dermis. Notably, almost all inflammatory cells in the dermis were negative for CXCL16. MATERIALS AND METHODS: Ten paraffinized specimens of human lesional psoriatic skin and five paraffinized specimens of normal skin were studied using an immunohistochemical streptavidinperoxidase technique. CONCLUSION: We here report for the first time alterations in the immunohistochemical staining pattern of CXCL16 in lesional psoriatic skin compared to the normal skin. These results suggest that CXCL16 may play a role in the pathogenesis of psoriasis.

The Expression of NMDA Receptor 1 Correlates with Clinicopathological Parameters in Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Ionotropic glutamate receptors of the N-methyl-D-aspartate receptor (NMDAR) type are expressed on keratinocytes and play a role in the proliferation, differentiation, and cornification of keratinocytes. However, the expression profile of NMDAR and its role in cutaneous malignancy is unclear. OBJECTIVE: We analyzed the expression of NMDAR-1 in cutaneous squamous cell carcinoma (SCC) and investigated the relationship between NMDAR-1 expression and clinicopathological parameters. METHODS: Thirty-two patients with biopsy-proven cutaneous SCC were enrolled in this study. Each patient was analyzed for tumor diameter, location, local recurrence, and metastasis by conducting a chart review. The SCC specimens were histologically divided into differentiated and undifferentiated groups based on Broders' system. NMDAR-1 expression was examined by performing immunohistochemistry, and the relative staining intensity in the SCCs was graded into 5 levels. According to the staining intensity of NMDAR-1, the specimens were categorized into two groups: the higher group and the lower group. RESULTS: Fifteen (88%) of 17 tumors in the higher group were differentiated SCC, whereas 14 (93%) of 15 tumors in the lower group were undifferentiated SCC. In addition, NMDAR-1 expression was inversely correlated with metastasis (p=0.049). Local recurrence was associated with a lower staining intensity, but the results were not statistically significant. CONCLUSION: Our results demonstrate that NMDAR-1 expression in cutaneous SCC is significantly correlated with its differentiation and metastasis. Therefore, it may be a prognostic indicator for cutaneous SCC.

A case of steatocystoma multiplex limited to the scalp.

We report here on a 63-year-old woman who had several small, yellowish papules on the scalp for the previous 2 years. There was no family history of similar lesions. Yellowish, creamy material was expressed from a papule during punch biopsy. Histologic examination from the lesion revealed the typical features of steatocystoma multiplex. We report here on this rare variant of steatocystoma multiplex that was limited to the scalp.