Herpes simplex virus mucocutaneous tumoural lesions - Systematic review.

The goal was to characterize the clinical-epidemiological profile of patients with mucocutaneous tumoural herpes simplex virus (MCT HSV) lesions across the world. Two researchers extracted and independently reviewed data from the literature search engine PubMed/MEDLINE through October 2018. From 110 reported patients, the following data were available: the patients' ages ranged from 7 to 76 years; the majority was male (62.73 %-69/110) and immunosuppression was found in 97.25 % (106/109, missing 1) cases, of whom 88 were HIV- related. Lesions size varied from 0.2-13 cm, settling in the anogenital region in 76.36 % (84/110) patients; 84.13 % (53/63, missing 47) complained of pain and multiple recurrences were found in 44.94 % (40/89, missing 21) cases. On clinical basis, the initial hypothesis was neoplasia in 36/53 patients. Histopathological diagnosis was achieved in 90 % (90/100, missing 10) cases and was sample size-dependent. Type 2 HSV was detected in 86.07 % (68/79, missing 31) lesions. MCT HSV lesions recurrence after treatment was reported in 33.96 % (18/53, missing 57) patients. Pathophysiology is poorly understood. Physicians should be aware of MCT HSV lesions in immunosuppressed patients to avoid inappropriate therapeutic strategies.

Dermal vasculature and melanocytic proliferation index in photodamaged skin in the assessment of lateral margins of lentigo maligna and lentigo maligna melanoma.

Lentigo maligna (LM) is the most common subtype of melanoma on the face. When it invades the dermis it is called lentigo maligna melanoma (LMM). Its histological delimitation is controversial due to subjectivity. Analysis of peritumoral vasculature and proliferation index of melanocytes may help to differentiate tumor areas from tumor-free areas, as neoplasia-induced angiogenesis in such scenarios, as well as the higher proliferation index of melanocytes in melanomas, are well established. This work compares the peritumoral vasculature and melanocyte proliferation index of LM and LMM with that of adjacent non-neoplastic skin and sun-damaged skin (control). Forty-three resection cases of LM and LMM were selected retrospectively. Immunohistochemistry was performed for anti-CD31 and anti-CD105 to assess vascularization. Melanocyte proliferation index double labeling was performed using the anti-Melan-A and anti-Ki-67. The Chalkley optical grid was used to quantify blood vessel hotspots. Doubly labeled cells with anti-Melan-A and anti-Ki-67 were counted at tumor, free margin, and control skin. Microvasculature quantification under the melanomas, for both CD31 and CD105, was greater than at the margins of the same specimens (P < 0.0001; P = 0.0001) and greater than control skin (P = 0.0016; P = 0.0027), with higher density for CD31 than CD105. The mean number of double-labeled proliferating melanocytes at the melanoma periphery was greater than at the adjacent free skin and control skin (P = 0.0011). The control skin samples showed the highest CD31-positive vasculature in the head and neck region, with a positive correlation between melanocytic proliferation index and vasculature. The presence of neovascularization (CD105) and proliferating melanocytes (Ki67+/Melan-A+) are suspicious findings for LM/LMM, helping to outline, diagnose, and evaluate tumor margins.

Etapas da progressão do carcinoma espinocelular cutâneo: estudo imuno-histoquímico das proteínas p53 e Ki-67 e de marcadores endoteliais / Steps of progression in cutaneous squamous cell carcinoma: an immunohistochemical study of p53 and Ki67 proteins and endothelial markers

As etapas cruciais da carcinogênese cutânea incluem disfunção da proteína supressora tumoral p53 e angiogênese. A contribuição de tais eventos, individual e sinergicamente, ainda não está bem estabelecida na cascata de fenômenos que resultam no carcinoma espinocelular cutâneo. Objetivou-se avaliar a expressão imuno-histoquímica da p53, o índice proliferativo e a angiogênese nos estádios evolutivos do carcinoma espinocelular cutâneo, e investigar a relação da expressão da p53 com as demais variáveis. Foram estimadas as porcentagens de células imunomarcadas para p53 e Ki-67 em três grupos de cânceres: 30 queratoses solares, 30 carcinomas espinocelulares superficialmente invasores e 30 carcinomas espinocelulares invasores. O método Chalkley foi utilizado para quantificar a área microvascular, empregando-se marcador de neoangiogênese (CD105) e pan-endotelial (CD34) em cada grupo. A área microvascular em amostras marcadas pelo CD105 aumentou, significantemente, com a progressão do carcinoma espinocelular cutâneo. O mesmo não ocorreu com o uso do CD34. Contudo, nos três grupos (queratose solar, carcinoma espinocelular superficialmente invasor e invasor) encontrou-se aumento significante da área microvascular, com ambos os marcadores (CD34 e CD105), em comparação à respectiva pele adjacente. Não houve diferença significante na taxa de células positivas para p53 e Ki-67 entre os grupos. Encontrou-se correlação positiva e significante entre a área microvascular marcada pelo CD105 e o índice de marcação para a p53 no carcinoma espinocelular superficialmente invasor, bem como entre o índice de marcação para p53 e para o Ki-67 no carcinoma espinocelular invasor. A conversão angiogênica é um evento precoce no carcinoma espinocelular cutâneo, e a neovascularização é paralela à progressão do tumor. O uso do CD105 permite avaliar a atividade angiogênica no tumores escamosos. A angiogênese no estádio inicial da invasão e a atividade proliferativa na fase francamente invasora estão associadas com a expressão imuno-histoquímica da proteína p53. A perda da função supressora tumoral da p53, em etapas progressivas, atua diretamente na carcinogênese cutânea. (AU)

Multistep skin carcinogenesis crucially involves loss of function of p53 tumor suppressor protein and angiogenesis. The contribution of such events, individually and synergically, is not well established in the cascade of phenomena that results in cutaneous squamous cell carcinoma. We aimed to evaluate the immunohistochemical expression of p53, the proliferative index and angiogenesis in spectral stages of cutaneous squamous cell carcinoma, and investigate the relationship between p53 expression with the other variables. We estimated the percentages of immunostained cells for p53 and Ki-67 (proliferation marker) in three groups of cancer: 30 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by neoangiogenesis (CD105) and panendothelial (CD34) immunomarker in each group. The microvascular area in CD105-stained specimens significantly increased with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. There was no significant difference for the rate of p53- and Ki-67-positive cells between the groups. Significant positive correlation was found between the CD105 microvascular area and the rate of p53 positive cells in superficially invasive squamous cell carcinoma as well as between the rate of p53- and Ki-67-positive cells in invasive squamous cell carcinoma. The angiogenic switch is an early event in cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows evaluating angiogenic activity in squamous tumors. Neovascularization in the initial stage of invasion and proliferative activity in the frankly invasive stage were both associated with p53 immunoexpression. Loss of p53 tumor suppressor function through progressive steps is directly involved in skin carcinogenesis.(AU)

p53 immunoexpression in stepwise progression of cutaneous squamous cell carcinoma and correlation with angiogenesis and cellular proliferation.

Multistep carcinogenesis involves loss of function of tumor suppressor proteins such as p53 and induction of angiogenesis. Such mechanisms contribute to cutaneous squamous cell carcinoma progression and may be interconnected. We aimed to explore p53 immunoexpression in spectral stages of cutaneous squamous cell carcinoma and correlate expression to both neovascularization and cellular proliferation. We estimated the percentages of immunostained cells for p53 and Ki67 (proliferation marker) in three groups: 23 solar keratoses, 28 superficially invasive squamous cell carcinomas and 28 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by neoangiogenesis (CD105) immunomarker in each group. There was no significant difference for rate of p53- and Ki67-positive cells between groups. Significant positive correlation was found between the CD105 microvascular area and the rate of p53 positive cells in superficially invasive squamous cell carcinoma as well as between the rate of p53- and Ki67-positive cells in invasive squamous cell carcinoma. p53 and Ki67 immunoexpression did not increase with cutaneous squamous cell carcinoma progression. Neovascularization in the initial stage of invasion and proliferative activity in the frankly invasive stage were both associated with p53 immunoexpression. Loss of p53 tumor suppressor function through progressive steps may be directly involved in skin carcinogenesis.

Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers.

OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.

Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers

OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.