Expresión de Aurora Quinasa A, Aurora Quinasa B y Survivina en relación con el ciclo celular de las queratosis actínicas y de los carcinomas epidermoides de la piel

Resumen

El estudio de las moléculas reguladoras del ciclo celular de la familia Aurora quinasas y de la familia de Survivina se ha realizado en numerosos tumores y los datos obtenidos se han correlacionados con los marcadores clásicos de proliferación celular, incluidos el índice de Ki67 y la expresión del oncogén p53: Sin embargo, la evaluación inmunohistoquímica de estas moléculas, incluidas Aurora A, Aurora B, Survivina y Fosfosurvivina, han sido escasamente exploradas en los carcinomas epidermoides (CE) cutáneos, y, en nuestro conocimiento, no han sido cuantificadas en lesiones premalignas de queratosis actínicas. En la presente Tesis se compara la cuantificación de la expresión nuclear inmunoihistoquímica de Aurora A, Aurora B, Survivina y Fosfosurvivina en las áreas de CE bien diferenciados con respecto al índice de estos marcadores en las áreas de CE pobremente diferenciado. En el grupo de casos con queratosis actínica se evalúan los índices de estos marcadores con el patrón de expresión de la epidermis normal de los bordes quirúrgicos y con los dos grados histopatológicos de las aéreas bien y pobremente diferenciadas del CE. Los datos cuantitativos demuestran un significativo mayor número de núcleos Aurora A y Aurora B positivos en las áreas de CE pobremente diferenciadas que en las bien diferenciadas. También la expresión de Survivina es superior en las zonas con pobre diferenciación, pero contrariamente la expresión de Fosfosurvivina es ligeramente mayor en el patrón bien diferenciado del CE. En las queratosis actínicas, el número de células Aurora A y Aurora B positivas es mucho mayor que en la epidermis normal; sin embargo, el alto número de núcleos Aurora A positivos en las queratosis actínicas no llega a alcanzar los altos valores encontrados en las áreas de CE bien diferenciado. Contrariamente la cuantificación de núcleos Aurora B positivos demuestra un significativo mayor número en las queratosis actínicas que en las zonas bien diferenciadas los CE, no habiendo encontrado significación cuando se compara con los patrones de CE pobremente diferenciado. En las lesiones intradérmicas de queratosis actínicas, la expresión de Survivina y Fosfosurvivina es significativamente mayor que en la epidermis normal; además, el alto índice de Survivina observado en las lesiones queratósicas es significativamente menor cuando se compara con los dos patrones bien y pobremente diferenciados de CE. La cuantificación de Fosfosurvivina de las queratosis actínicas demuestra índices significativamente mayores que los obtenidos en los dos tipos de CE cutáneos. Los datos obtenidos en este estudio sugieren un comportamiento diferente de estas moléculas reguladoras del ciclo celular en las lesiones premalignas cutáneas de queratosis actínicas y en los dos tipos bien diferenciado y pobremente diferenciado de CE. Además, estos datos inmunohistoquímicos y cuantitativos pudieran tener relación con el diferente comportamiento biológico y con el pronóstico de estos tumores cutáneos Regulating proteins of the cellular cycle related to Aurora Kinase and Survivin have been studied in different tumors, and have been correlated with the most common proliferation cell markers, including Ki67 index and the p53 oncogen expresion. However, immunohistochemical evaluation of these proteins, including Aurora A, Aurora B, Survivin and Phospho-Survivin, have been scarcely explored in Squamous Cell Carcinoma (SCC). As far as we know, these proteins have not been quantified in premalignant skin lesions, such as Actinic Keratoses. This Thesis research compares the quantification of immunohistochemical nuclear expression of Aurora A, Aurora B, Survivin and Phospho-Survivin in the areas with welldifferentiated SCC pattern regarding to the level of these markers in areas affected with poorly-differentiated SCC. In the Actinic Keratoses cases, levels of these markers were compared with those observed in the surgical borders containing normal epidermis, as well as with the two histopathological well and poorly-differentiated grades of SCC. Quantitative data show a higher number of positive Aurora A and Aurora B cells in poorly-differentiated SCC areas than in well-differentiated pattern of SCC. Survivin expression is also higher in poorly-differentiated tumors. On the contrary, Phospho-Survivin expression is slightly higher in the well-differentiated SCC pattern. The number of positive Aurora A and Aurora B cells is much higher in Actinic Keratoses than in normal epidermis. Nevertheless, the amount of Aurora A in Actinic Keratoses does not reach the high levels found in the areas of well-differentiated SCC. On contrary, quantification of positive Aurora B nuclei shows a significant higher level in Actinic Keratoses than observed in the well-differentiated SCC pattern; however, levels of Aurora B index were similar in Actinic Keratoses compared with obtained in areas of poorly-differentiated SCC. In intradermal lesions of Actinic Keratoses, Survivin and Phospho-Survivin expression is significantly higher than in normal epidermis; and the high level of Survivin in the Actinic Keratoses is significantly lower when comparing with well and poorly-differentiated patterns of SCC. Quantification of Phospho-Survivin in Actinic Keratoses shows significantly higher levels than the results obtained from both types of cutaneous SCC. Regulating proteins of the cellular cycle related to Aurora Kinase and Survivin have been studied in different tumors, and have been correlated with the most common proliferation cell markers, including Ki67 index and the p53 oncogen expresion. However, immunohistochemical evaluation of these proteins, including Aurora A, Aurora B, Survivin and Phospho-Survivin, have been scarcely explored in Squamous Cell Carcinoma (SCC). As far as we know, these proteins have not been quantified in premalignant skin lesions, such as Actinic Keratoses. This Thesis research compares the quantification of immunohistochemical nuclear expression of Aurora A, Aurora B, Survivin and Phospho-Survivin in the areas with welldifferentiated SCC pattern regarding to the level of these markers in areas affected with poorly-differentiated SCC. In the Actinic Keratoses cases, levels of these markers were compared with those observed in the surgical borders containing normal epidermis, as well as with the two histopathological well and poorly-differentiated grades of SCC. Quantitative data show a higher number of positive Aurora A and Aurora B cells in poorly-differentiated SCC areas than in well-differentiated pattern of SCC. Survivin expression is also higher in poorly-differentiated tumors. On the contrary, Phospho-Survivin expression is slightly higher in the well-differentiated SCC pattern. The number of positive Aurora A and Aurora B cells is much higher in Actinic Keratoses than in normal epidermis. Nevertheless, the amount of Aurora A in Actinic Keratoses does not reach the high levels found in the areas of well-differentiated SCC. On contrary, quantification of positive Aurora B nuclei shows a significant higher level in Actinic Keratoses than observed in the well-differentiated SCC pattern; however, levels of Aurora B index were similar in Actinic Keratoses compared with obtained in areas of poorly-differentiated SCC. In intradermal lesions of Actinic Keratoses, Survivin and Phospho-Survivin expression is significantly higher than in normal epidermis; and the high level of Survivin in the Actinic Keratoses is significantly lower when comparing with well and poorly-differentiated patterns of SCC. Quantification of Phospho-Survivin in Actinic Keratoses shows significantly higher levels than the results obtained from both types of cutaneous SCC.