{"id":117578,"date":"2015-05-06T00:00:00","date_gmt":"2015-05-06T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/patologa%c2%ada-cervical-valor-predictivo-de-la-tecnica-inmunocitoqua%c2%admica-p16-ki67-para-detectar-lesiones-cin2-subyacente\/"},"modified":"2015-05-06T00:00:00","modified_gmt":"2015-05-06T00:00:00","slug":"patologa%c2%ada-cervical-valor-predictivo-de-la-tecnica-inmunocitoqua%c2%admica-p16-ki67-para-detectar-lesiones-cin2-subyacente","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ginecologia\/patologa%c2%ada-cervical-valor-predictivo-de-la-tecnica-inmunocitoqua%c2%admica-p16-ki67-para-detectar-lesiones-cin2-subyacente\/","title":{"rendered":"Patolog\u00eda cervical. \u00abvalor predictivo de la t\u00e9cnica inmunocitoqu\u00edmica p16\/ki67 para detectar lesiones cin2+ subyacente\u00bb"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Mar\u00eda  Amparo Torroba Caron <\/strong><\/h2>\n<p>Resumen  el carcinoma de c\u00e9rvix representa la tercera neoplasia m\u00e1s frecuente en el mundo en las mujeres y una de las causas principales de muerte en pa\u00edses en v\u00edas de desarrollo. El virus del papiloma humano (vph) es causa necesaria pero no suficiente para el desarrollo de esta neoplasia, puesto que casi todos los casos diagnosticados (99%) resultan positivos. Est\u00e1 totalmente asumido que el screening peri\u00f3dico con el test de papanicolau es efectivo en reducir la incidencia y mortalidad del c\u00e1ncer cervical, aunque en ocasiones puede presentar baja sensibilidad. La determinaci\u00f3n de vph-ar aporta baja especificidad, dado que la mayor\u00eda de infecciones por vph son transitorias (hasta un 90% de las infecciones se aclaran en los dos primeros a\u00f1os).  nuestro estudio versar\u00e1 de c\u00f3mo un marcador dual inmunocitoqu\u00edmico (p16\/ki67) puede indicar la desregulaci\u00f3n del ciclo celular causado por oncoprote\u00ednas del vph: e6 y e7.  objetivos: \t el objetivo principal de esta tesis es: o\tcomprobar si la tinci\u00f3n dual con biomarcadores p16ink4a  y ki-67 que se expresan en las c\u00e9lulas de las citolog\u00edas diagnosticadas de asc y lsil se asocia bien con lesi\u00f3n cin2+ subyacente, o con progresi\u00f3n en un per\u00edodo determinado a cin2+  y los objetivos secundarios: o\tcomparar la tasa de positividad, sensibilidad y especificidad para citolog\u00eda con tinci\u00f3n dual versus determinaci\u00f3nvph-ar, para detectar lesiones cin2+ o\tver qu\u00e9 relaci\u00f3n guarda la positividad de la t\u00e9cnica dual p16\/ki-67 con los distintos genotipos virales de alto riesgo, en los casos confirmados histol\u00f3gicamente como cin2+. Frecuencia de los distintos genotipos en estas lesiones\t  metodolog\u00eda general: &quot;\tobjetivo principal: se seleccionaron 306 pacientes a las que se les realiz\u00f3 t\u00e9cnica dual inmunocitoqu\u00edmica p16\/ki-67. Tras su realizaci\u00f3n se valor\u00f3 como positiva o negativa. De las 306 muestras citol\u00f3gicas, el 50% de ellas se sigui\u00f3 de toma bi\u00f3psica, con tres posibles diagn\u00f3sticos: negativo para displasia (16), cin1 (80) y cin2+ (57). o\tel &quot;gold standard&quot; es el diagn\u00f3stico histol\u00f3gico de cin2+ o\tel seguimiento de las pacientes fue de 1 d\u00eda hasta 30 meses en alg\u00fan caso &quot;\tobjetivo  n\u00c2\u00ba2: a 146 pacientes de las 306 se les realiz\u00f3 adem\u00e1s tests de vph: captura h\u00edbrida (hc2) y genotipado por pcr (clart\u00c2\u00bf hpv2).  &quot;\tobjetivo n\u00c2\u00ba3: de las 57 pacientes en las que se confirmaron histol\u00f3gicamente lesiones de cin2+ se enviaron cortes de tejidos embebidos en parafina (tep) a la unidad de virolog\u00eda para genotipado con pcr (m\u00e9todo clart\u00c2\u00bf). resultados: \tobjetivo principal: o\tse obtiene un aumento significativo de la sensibilidad para detectar lesi\u00f3n cin2+ subyacente, manteniendo la alta especificidad que ya aportaba el test de papanicolau por s\u00ed solo. o\tse observan leves diferencias en sensibilidad\/especificidad entre los asc y los lsil objetivo n\u00c2\u00ba 2: \t\tse observa, tanto en asc como en lsil, una similar sensibilidad entre ambos tests (t\u00e9cnica dual y determinaci\u00f3n de vph) para detectar lesi\u00f3n cin2+ subyacente cercana al 90%, existiendo sin embargo una especificidad mayor para la t\u00e9cnica dual, estad\u00edsticamente significativa. objetivo n\u00c2\u00ba3: \tse diagnostic\u00f3 cin2+ en 57 pacientes de las 306 inclu\u00eddas en el estudio (18,6%). En m\u00e1s de la mitad de los casos (el 56%) la infecci\u00f3n fue por un \u00fanico genotipo, siendo el m\u00e1s frecuente el 16 (en 14 pacientes, el 50% de los casos positivos para vph-ar), seguido del 31, y despu\u00e9s con la misma frecuencia el 18, 45, 51 y 58. \ten los casos de infecci\u00f3n m\u00faltiple tambi\u00e9n es el genotipo 16 el que m\u00e1s frecuentemente se asocia con otros genotipos (hasta en un 59% de los casos). El vph 18 s\u00f3lo aparece asociado en un 18% con otros genotipos. \tla frecuencia absoluta ha sido para el vph16, seguido del 31 y posteriormente del 18.     summary  cervical cancer is the third most common neoplasia in women and still is one of the main causes of death in less developed countries. Human papillomavirus (hpv) is necessary but not sufficient cause for this neoplasia as almost all the diagnosed cases (99%) were positive for cervical cancer. Regular screening together with the performance of a pap test are believed to be effective in lowering cervical cancer incidence and mortality rates, although it can show low sensitivity. Hr-hpv tests have a low specificity as most hpv infections are temporary (up to 90% of the infections resolve within the first two years).  \tour study will deal with how immunocytochemistry involving dual staining for p16 and ki-67 can show cell cycle deregulation caused by hpv oncoproteins: e7 inactivates prb, so p16 overexpression increases dramatically, and e6 stimulates the proliferative activity of ki-67 by interfering with p53.   objectives: \t the main objective of this thesis is to: o\tcheck that dual staining of asc and lsil cytology with p16ink4a and ki-67 biomarkers is associated with an underlying cin2+ lesion, or is progressing to cin2+ over a specific period of time.  and the following secondary objectives: o\tcomparing positivity, sensitivity and specificity rates for positive, dual stained results for dual staining cytology to determination of hr-hpv, in order to detect cin2+ lesions.   o\tobserving the connection of positive dual-stained results for p16 and ki-67 with the different high-risk viral genotypes in histologically confirmed cases of cin2+. Frequency with which different genotypes appear in these lesions.  materials and methods  &quot;\tmain objective: 306 selected patients underwent p16\/ki-67 dual immunostaining testing. The tests were positive or negative. Out of the 306 cytology samples, 50% were followed by bioptic sampling (histological analysis of 153 patients), with three possible diagnoses: negative for dysplasia (16), cin1 (80) and cin2+ (57).  o\tthe gold standard is the histologic diagnosis of cin2+. o\tthe clinical follow-up of patients took from 1 day up to 30 months in some cases.   &quot;\tobjective no.2: 146 patients underwent hpv testing as well:  digene hybrid capture (hc 2) test and a pcr-based genotyping assay (clart\u00c2\u00bf hpv2). &quot;\tobjective no.3: sections of paraffin-embedded tissues from the 57 patients were sent to the department of virology for a pcr-based genotyping assay (clart\u00c2\u00bf hpv2).  results: main objective: o\tthree hundred and forty-nine p16\/ki-67 dual-stained cytology tests were performed in 306 patients with asc and lsil diagnoses, resulting in a general and important rise in sensitivity for the detection of an underlying cin2+ lesion, maintaining the same high specificity given only by the pap test.   o\tsome minor differences in sensitivity and specificity are found in asc and lsil. objective no. 2: \tin asc and lsil, both tests (dual staining and determination of hpv) have a similar sensitivity of 90% when detecting any underlying cin2+ lesion, although a statistically significantly higher specificity of dual stained cytology has been observed. objective no. 3: \tcin2+ has been diagnosed in 57 patients out of the 306 patients who participated in this study (18,6%). In more than half of the cases (56%), the infection was due to only one genotype, the most common being genotype 16 (in 14 patients or 50% of the hr-hpv-positive cases), followed by genotype 31 and then genotypes 18, 45, 51 and 58 with the same frequency. \tin cases of multiple infection, it is also genotype 16 which is most frequently associated with other genotypes (in up to 59% of the cases). Hpv-18 is only associated with other genotypes in 18% of the cases.  \tin order, the following absolute frequency was observed: hpv-16, 31 and finally 18.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Patolog\u00eda cervical. \u00abvalor predictivo de la t\u00e9cnica inmunocitoqu\u00edmica p16\/ki67 para detectar lesiones cin2+ subyacente\u00bb<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Patolog\u00eda cervical. \u00abvalor predictivo de la t\u00e9cnica inmunocitoqu\u00edmica p16\/ki67 para detectar lesiones cin2+ subyacente\u00bb <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Mar\u00eda  Amparo Torroba Caron <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 05\/06\/2015<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Enrique Poblet Martinez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: vicente Vicente ortega <\/li>\n<li>\u00c1lvaro Zapico go\u00f1i (vocal)<\/li>\n<li>Jos\u00e9 Garcia solano (vocal)<\/li>\n<li>roberto Matorras weinig (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Mar\u00eda Amparo Torroba Caron Resumen el carcinoma de c\u00e9rvix representa la tercera neoplasia m\u00e1s frecuente en el 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