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
Author
Ágreda Ulloa, LuisEntity
UAM. Departamento de Anatomía PatológicaDate
2015-02-26Subjects
Piel - Cáncer - Tesis doctorales; Queratosis actínica - Tesis doctorales; MedicinaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Anatomía Patológica. Fecha de lectura: 26-02-2015Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
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.
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