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ABSTRACT: We evaluated the role of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and hypoxia-inducible factor 1-a (HIF1-a) in melanoma angiogenesis and investigated their expression in dysplastic nevi, as potential melanoma precursors. In addition, we examined a possible correlation of VEGF expression with PlGF and HIF1-a. These factors were detected immunohistochemically in 95 melanomas of all types and stages and in 28 dysplastic nevi. We used 10 intradermal melanocytic nevi as controls. HIF1-a was expressed in 93 out of 95 (97.89%) melanomas and in none of the dysplastic or control nevi. HIF1-a expression was more intense in melanocytes around necrotic areas but did not correlate with melanoma type, the Clark staging or the Breslow thickness. A strong positive association was detected between HIF1-a and VEGF expression in all cases. VEGF was detected in 82 out of 95 (86.31%) melanomas and in 21 out of 28 (75%) dysplastic nevi, whereas it was expressed weakly in neoplastic cells of the controls. Its expression was more intense in melanomas, especially in nodular melanomas of elevated stage and thickness. PIGF was detected in 46 out of 95 (48.42%) melanomas and in none of the nevi. Expression did not correlate with melanoma staging nor thickness; however, it was more intense in superficial spreading melanomas, where a weak positive association between VEGF and PlGF was also detected. There was no association between HIF1-a and PlGF in any melanoma type. Hypoxia, through the expression of HIF1-a, plays a key role in melanoma progression; it activates VEGF secretion, which induces angiogenesis and metastasis. The role of PlGF seems to be limited.
Melanoma research 10/2011; 21(5):389-94. · 2.06 Impact Factor
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ABSTRACT: The aim of the study was to investigate the expression of PGP 9.5 in cutaneous keratoacanthomas (KAs) and squamous cell carcinomas (SCCs). Thirty-one cases of KA (10 in the growth stage, 9 in the mature phase and 12 in the involution stage) and 36 SCCs including 13 well differentiated cases, 12 moderately differentiated tumors, 7 poorly differentiated lesions and 4 pseudoadenoid entities were investigated. PGP 9.5 expression was positively correlated with tumor stage (P < 0.001) and potential perineural invasion (P < 0.001). There was no significant difference in the distribution of patients presenting variable levels of PGP 9.5 staining with regard to maximal tumor size and the extent and degree of stromal invasion. PGP 9.5 expression proved closely associated with tumor aggressiveness and is classified as a marker for predicting the outcome of resection-treated skin cancer patients.
Archives for Dermatological Research 06/2009; 301(9):653-8. · 2.28 Impact Factor
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ABSTRACT: squamous cell carcinoma (SCC) consists of altered keratinocytes, presents variable differentiation, inexorably progresses, and on occasion metastasizes.
to investigate the biological activity of epidermal cells in SCCs by estimating the expression of PGP 9.5 and cyclin D1 using immunohistochemistry. Methods: the sample included 13 well-differentiated cases of cutaneous SCC (grade I), 12 moderately differentiated tumors (grade II), and 7 poorly differentiated lesions (grade III). Four cases belonged to the distinct entity of pseudoadenoid SCC.
PGP 9.5 expression was positively correlated with tumor stage (P < .001) and potential perineural invasion ( P < .001), whereas cyclin D1 expression correlated inversely with the degree of cellular differentiation (P < .001) and PGP 9.5 immunostaining (P < .001).
PGP 9.5 and cyclin D1 coexpression was closely associated with tumor aggressiveness and can be classified as a marker for predicting the outcome of resection-treated skin cancer patients.
International Journal of Surgical Pathology 06/2009; 17(6):413-20. · 1.00 Impact Factor
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ABSTRACT: In the present study we evaluated, in involved and clinically uninvolved skin of Rosacea, microvessels density (MVD) and total vascular area (TVA) in addition to multiple morphologic characteristics of microvessels and also mast cells (MCs) number. We examined also the relationship between angiogenesis, MCs number and disease clinicopathological data. The study included 69 patients with Rosacea. A skin biopsy with a 4-mm punch was performed from clinically involved skin in each case. In nine randomly selected patients, facial biopsy specimens were obtained from both involved and clinically uninvolved skin. Histological sections, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, TVA and several morphometric parameters related to the vessel size or shape. MCs detection in the dermis was carried out using the chloracetate esterase method (Fast Blue RR) in parafin sections. Serum antibodies against H.pylori were detected. Statistically important differences concerning the factors of angiogenesis between lesional and clinically non-lesional skin were demonstrated. A statistical important correlation was found also between high vascular density, PPR clinical type and the presence of ocular manifestations. MVD or TVA showed no correlation with the degree of solar elastosis or inflammation and with the Demodex density as well. However, high MVD values were found to correlate with granuloma formation in the dermis. MCs number were significantly greater in lesional compared to clinically non-lesional skin. Statistical significance was shown between MCs density and disease duration. However, no correlation between MCs number and blood vessel density was found. Angiogenesis seems to play an important role in the pathogenesis especially of the more severe clinical form of Rosacea. MCs seem to participate in evolution to disease chronicity by contributing to inflammation, angiogenesis and tissue fibrosis.
Archives for Dermatological Research 04/2008; 300(3):125-31. · 2.28 Impact Factor
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Acta Dermato Venereologica 02/2008; 88(2):191-2. · 3.18 Impact Factor
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International Journal of Dermatology 01/2008; 46(12):1321-2. · 1.14 Impact Factor
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ABSTRACT: The aim of this study was to investigate the biologic activity of epidermal cells in keratoacanthomas (KAs) and squamous cell carcinomas (SCCs) by counting the number of silver-stained nucleolar organizer regions (AgNORs), to estimate the quantity of Ig-producing cells and the inflammatory cellular infiltrate (ICI), and to make a comparative evaluation. Thirty KAs (10 at growth stage, 10 at mature stage, and 10 at involution stage) and 28 SCCs (nine well differentiated-Grade 1 (G1), seven moderately differentiated-Grade 2 (G2), five poorly differentiated-Grade 3 (G3), and seven pseudoadenoid) were investigated. The KAs examined had a mean number of 1.727 AgNORs (S.D. 0.232), and IgG predominated in most cases. IgG and IgE increase at the involution, IgA remains at almost the same level, and IgM decreases during the maturity stage. The SCCs examined had a mean number of 2.105 AgNORs (S.D. 0.446). IgG predominated and gradually increased in proportion to the degree of malignancy. There is a significant difference in the number of AgNORs and the proportion of Ig subclasses in contrast to the cellular infiltrate among the three stages of KA. In SCCs, the number of AgNORs and the percentage of Igs and ICI increased gradually in proportion to the degree of malignancy.
Pathology - Research and Practice 02/2007; 203(9):659-65. · 1.21 Impact Factor
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ABSTRACT: This study was conducted to elucidate the biological activity of epidermal cells in cutaneous squamocellular tumors by counting the number of silver-stained nucleolar organizer regions (AgNORs), to estimate the quantity of Ig-producing cells and the inflammatory cellular infiltrate (ICI), and to achieve a comparative evaluation. Twenty cases of actinic keratosis (AK), 20 in situ squamous cell carcinomas (ISC), and 20 invasive squamous cell carcinomas (SCCs) were assessed using a silver colloid technique. Ig-producing or binding cells and ICI were also investigated immunohistochemically. In all samples, AgNORs, Ig-producing cells, and ICI increased in proportion to the degree of malignancy. With regard to AgNORs values, a statistically significant difference was confirmed between AK and ISC (p<0.01), AK and SCC (p<0.001), and ISC and SCC (p<0.05). IgG-producing cells predominated in each case. Furthermore, a linear correlation was detected between ICI and AgNORs in AK and ISC. The significant difference in the number of AgNORs among the 3 stages of involution of SCC reinforces the value of AgNORs as a marker for malignant potential. Despite the absence of a correlation between AgNORs and the proportion of Ig-producing cells, the association between ICI and AgNORs in AK and ISC was obvious.
Pathology - Research and Practice 01/2007; 203(12):857-62. · 1.21 Impact Factor
