Hypoxia-inducible factors 1alpha and 2alpha are related to vascular endothelial growth factor expression and a poorer prognosis in nodular malignant melanomas of the skin.

Hypoxia is a key regulatory factor in tumour growth, activating angiogenesis, glycolysis and cell migration. It is readily recognized by the intracellular accumulation of hypoxia-inducible factor 1alpha (HIF1alpha) and HIF2alpha. Accumulation of HIF1alpha and HIF2alpha was detected immunohistochemically in a series of 46 nodular malignant melanomas of the skin (epithelioid cell variant), treated with wide local excision. The results were correlated with vascular density (VD) and expression of the angiogenesis-stimulating factors vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). Further associations were sought with patient prognosis and the important histopathological features of Breslow's thickness, Clark's level of invasion, mitotic rate, inflammatory cell infiltrates and tumour ulceration. HIF1alpha and HIF2alpha accumulation in malignant melanomas was directly correlated with VEGF expression. Tumours with high VEGF or HIF2alpha expression were associated with a poorer prognosis on both univariate and multivariate analyses. Tumours displaying high VD were also associated with a poor prognosis, but only on univariate analysis. Such vascularized malignant melanomas had only a limited inflammatory cell response. TP and VEGF were frequently co-expressed. The value of Breslow's thickness and Clark's level in prognosis was reaffirmed, although only on univariate analysis. Overexpression of the transcription factors HIF1alpha and HIF2alpha are linked to VEGF expression in nodular malignant melanomas. Loss of immune surveillance, as indicated by a limited inflammatory cell response, was also associated with high angiogenic activity. HIF2alpha, VEGF and, to a lesser extent, VD are important prognostic factors in these cutaneous tumours

Identification of human papillomavirus DNA in melanoma biopsy specimens of Greek population

The aim of this retrospective study was to evaluate melanoma biopsy specimens from the Greek population living in the prefecture of Larissa for the presence of human papillomavirus (HPV) DNA and to determine the possible relationship between HPV and clinical outcome in these patients. Twenty-eight melanoma biopsy specimens, 20 from primary cutaneous melanoma and eight from melanoma metastasis were obtained from 28 patients. The biopsy samples were formalin-fixed and paraffin wax-embedded. The control group consisted of three junctional melanocytic nevi, histologically confirmed, and three punch biopsies from normal skin that were obtained from six healthy individuals. The presence and types of HPV DNA were assessed by the amplification of a fragment of the L1 region by consensus primer polymerase chain reaction (PCR) combined with restriction fragment length polymorphism analysis (RFLPA). In each biopsy specimen that was evaluated, HPV 6, HPV 11, HPV 16 and HPV 18 positive controls from genital HPV lesions were included. Five of 28 (17.85%) biopsy melanoma specimens were positive for HPV DNA. Conversely, HPV was not detected in any of the biopsy specimens of the control group (0/6). HPV viral type 16 was found in two samples and HPV 6 DNA in three. Our results regarding the possible relationship between melanoma and HPV DNA were not statistically significant (p > 0.05). These findings suggest that ultraviolet sun exposure remains the main cause of melanoma in our region. The role of cutaneous HPV infection in the pathogenesis of melanoma remains elusive. © 2005 Bioscience Ediprint Inc

Calcipotriol monotherapy versus calcipotriol plus UVA1 versus calcipotriol plus narrow-band UVB in the treatment of psoriasis

The purpose of this study was to evaluate the efficacy of calcipotriol ointment as monotherapy versus calcipotriol in combination with narrow-band ultraviolet (UV)-B or UVA1 phototherapy and to determine whether calcipotriol in combination with UVA1 is an alternative to calcipotriol with narrow-band UVB phototherapy Forty-five patients with plaque psoriasis were divided into three treatment groups with no significant differences in Psoriasis Area and Severity Index (PASI) scores, mean age, sex or skin type. The total duration of the treatment was 3 months. Regarding PASI score, psoriasis regression was statistically significant between the groups. The response to UVA1 and narrow band UVB with calcipotriol was superior to calcipotriol monotherapy. UVA1 phototherapy with calcipotriol could be an alternative to narrow-band UVB phototherapy with calcipotriol

Correlation between maternal first trimester plasma leptin levels and birth weight among normotensive and preeclamptic women

Objective. To determine the connection between maternal first trimester serum leptin levels and newborn weight. Methods.The study included 37 preeclamptic women and 53 normotensive women who considered the control group. Maternal blood samples were withdrawn at 13 weeks of gestation for the measurement of leptin concentrations. Birth weights were transformed to z-scores according to maternal and obstetrical features, based on customised centiles. Non-parametric tests, student's t-test, Pearson's correlation, Spearman's correlation and linear regression analysis were performed in our analysis. Results.Pre-pregnancy body mass index and first trimester maternal plasma leptin levels were significantly higher among women with preeclampsia (p=0.015 and p<0.001, respectively). Birth weight z-score was negatively correlated with leptin levels (r-0.570, p<0.001), in preeclamptic group and in control group (r-0.477, p<0.001). The regression modelling demonstrated a significant negative association between birth weight z-scores and leptin for both groups. Conclusion.Maternal first trimester serum leptin demonstrates a significant negative association with neonatal weight in preeclamptic pregnancies and to a lesser extent in normotensive pregnancies. A possible leptin's involvement in pathophysiological adaptations that define the foetal growth potential can be supported. © 2010 Informa UK, Ltd

Evaluation of cytokine serum levels in patients with plaque-type psoriasis

Psoriasis is a chronic debilitating cutaneous disorder that affects both sexes and appears clinically as inflamed, edematous skin lesions covered with a silvery white scale. Strong evidence suggests that immune mechanisms are implicated in its pathogenesis, such as persistent activation of T-lymphocytes, excessive proliferation of keratinocytes and reactivation of proto-oncogenes and other elements. Additionally, several recent studies have demonstrated that cytokines play a significant role in the pathogenesis of the disease, as they can be found in the affected skin of psoriatic patients. In this study we evaluated levels of circulating cytokines in the serum of 45 Greek psoriatic patients before initiation of treatment and compared the results with those in 45 healthy volunteers. According to our findings interleukin (IL)-2, IL- 10, IL- 12 and tumor necrosis factor-alpha (TNF- alpha) levels were statistically significantly elevated in the serum of psoriatic patients before therapy compared with those of controls. IL-6 serum levels did not differ between psoriatic patients and healthy volunteers. Conversely, interferon-gamma serum levels of psoriatic patients were statistically significantly lower than those of healthy volunteers

Expression of 6 Common Antigenic Markers in Invasive Ductal Breast Carcinoma: Potential Clinical Implications

Expression of estrogen (ER) and progesterone receptors, c-erbB-2 oncogene, mutant p53 antioncogene (mp53), e-cadherin adhesion, and apoptotic caspase-8 antigens in tumor relative to matched normal tissue specimens from 102 unselected patients with primary ductal breast carcinoma of various tumor grades was assessed by immunohistochemistry and correlated with patient's biologic and clinical features, such as age, menstrual status, age of menarche, tumor grade and diameter, the presence or absence of metastases, and number of infiltrated lymph nodes. We observed association of e-cadherin adhesion, ER and progesterone antigen marker expression with low histologic grade tumors and limited number of lymph node metastases and of c-erbB-2, mp53, and casp-8 antigen marker expression with high histologic grade tumors and increased number of lymph node metastases. We also observed strong correlation (P < 0.05) between 4 of the 6 biomarkers and 4 of the 7 patient/tumor parameters examined. Our findings support the hypothesis of independent expression of these 4 strong biomarkers and reveal that nearly 40% of all breast tumor cases studied express similar proportions of 2 major phenotypic combinations [ER/c-erbB-2/mp53/casp-8: +/+/-/+ (19.6%) & +/-/-/+ (17.8%)]. We conclude that, in agreement with earlier reports, our findings support the diagnostic and potential prognostic value of these markers in the clinical assessment of breast cancer