Estudio piloto comparativo del test VPH con genotipado parcial en primera línea frente a otras estrategias de cribado poblacional del cáncer de cérvix. Estudio CRYGEN 16/18 / Comparative pilot study about HPV test with partial genotyping in primary screening versus other strategies for cervical cancer population screening, CRYGEN 16/18 study

Introducción: La detección precoz del cáncer de cérvix requiere la implementación de programas de cribado del virus del papiloma humano (VPH). Sin embargo, existen discrepancias en la optimización de esas estrategias. Se evalúa el rendimiento de 10 protocolos basados en técnicas moleculares, citológicas o combinadas en cribado primario. Material y métodos: Se diseña un estudio ciego, prospectivo e intervencionista en 1.977 mujeres de 35 años. La determinación molecular se realizó por la plataforma Cobas 4800HPV. Los análisis citológicos se realizaron en las mismas muestras sin conocimiento del resultado molecular. Todas las mujeres en las que se detectaba VPH-16/VPH-18 o presentaban alteración citológica y detección de otros genotipos de alto riesgo (VPHar) eran derivadas a colposcopia. Resultados: El ensayo molecular detectó presencia de VPHar en el 12,5% de las mujeres, mientras solo el 8,1% de las citologías fueron patológicas. El 19,5% de las pacientes derivadas a colposcopia revelaron lesiones de alto grado, estando VPH-16 presente en el 65,3% de ellas. En 6 de esas ocasiones (VPH-16 siempre presente) la citología había sido informada como normal. El seguimiento al año de las mujeres con citología normal y detección de VPHar identificó una lesión HSIL/CIN2+(asociada a VPH-33). En el estudio comparativo con otras estrategias el protocolo denominado CRYGEN 16/18 rindió el mejor equilibrio de sensibilidad y especificidad con la menor derivación a colposcopia. Conclusiones. La realización de detección molecular de VPH con genotipado parcial en primera línea, al menos VPH-16, con derivación directa a colposcopia, aumenta la tasa de detección de lesiones HSIL/CIN2+.(AU)

Introduction: The early detection of cervical cancer requires the implementation of molecular screening programs for human papillomavirus (HPV). However, there are discrepancies in the optimization of screening protocols. The performance of 10 primary screening strategies based on molecular, cytological or combined techniques is now evaluated. Material and methods: A blind, prospective, and interventional study was designed in 1977 35-year-old women. The molecular determination was carried out by the Cobas 4800 HPV platform. Cytological analysis was performed on the same samples without knowledge of the result of the molecular assay. All women in whom HPV-16/HPV-18 was detected or presented cytological alteration together with detection of other high-risk genotypes (HPVhr) were referred to colposcopy. Results: The molecular assay detected the presence of HPVhr genotypes in 12.5% of the women, while only 8.1% of the cytologies were pathological. Among the patients referred to colposcopy, in 19.5% high-grade lesions were observed, being HPV-16 present in 65.3% of them. In six of these high-grade lesions (associated with HPV-16 in all cases), cytology was reported as normal. The follow-up one year later, of women with normal cytology and HPVhr detection a HSIL/CIN2+ lesion was detected (associated to HPV-33). In the comparative study with other strategies, the protocol called CRYGEN 16/18 yielded the best balance of sensitivity and specificity with the least referral to colposcopy. Conclusions: Performing molecular detection of HPVhr with partial first-line genotyping of at least HPV-16, with direct referral to colposcopy, increases the detection rate of HSIL/CIN2+ lesions.(AU)

Comparative pilot study about HPV test with partial genotyping in primary screening versus other strategies for cervical cancer population screening, CRYGEN 16/18 study.

INTRODUCTION: The early detection of cervical cancer requires the implementation of molecular screening programmes for human papillomavirus (HPV). However, there are discrepancies in the optimization of screening protocols. The performance of 10 primary screening strategies based on molecular, cytological or combined techniques is now evaluated. MATERIAL AND METHODS: A blind, prospective, and interventional study was designed in 1.977 35-year-old women. The molecular determination was carried out by the Cobas 4800 HPV platform. Cytological analysis were performed on the same samples without knowledge of the result of the molecular assay. All women in whom HPV-16/HPV-18 was detected or presented cytological alteration together with detection of other high-risk genotypes (HPVhr) were referred to colposcopy. RESULTS: The molecular assay detected the presence of HPVhr genotypes in 12.5% of the women, while only 8.1% of the cytologies were pathological. Among the patients referred to colposcopy, in 19.5% high-grade lesions were observed, being HPV-16 present in 65.3% of them. In six of these high-grade lesions (associated with HPV-16 in all cases), cytology was reported as normal. The follow-up one year later, of women with normal cytology and HPVhr detection a HSIL/CIN2+ lesion was detected (associated to HPV-33). In the comparative study with other strategies, the protocol called CRYGEN 16/18 yielded the best balance of sensitivity and specificity with the least referral to colposcopy. CONCLUSIONS: Performing molecular detection of HPVhr with partial first-line genotyping of at least HPV-16, with direct referral to colposcopy, increases the detection rate of HSIL/CIN2+ lesions.

Risk Factors Associated with CIN2+ in Spanish Patients with L-SIL/ASCUS Cytology Collected from a Madrid Hospital.

The management of patients with L-SIL/ASCUS cytology is controversial and not clearly standardized. OBJECTIVE: To analyze the risk factors associated with H-SIL/CIN2+ in a cohort of patients with ASCUS or L-SIL in a Pap smear. METHODS: Between 2012 and 2022, 1259 eligible women with ASCUS/L-SIL were referred for colposcopy. The risk factors associated with H-SIL/CIN2+ were analyzed. The colposcopic study, conventional or assisted with dynamic spectral imaging (DSI), was performed in all cases. Guided biopsies were performed in cases of abnormal examination or random biopsies when no lesions were found. A LEEP was performed in H-SIL/CIN2+ results or persistent LSIL/CIN. RESULTS: A normal or metaplastic specimen was found in 750 women (63.2%), LSIL/CIN1 in 346 (29.1%), and H-SIL/CIN2+ in 92 (7.7%). The presence of HR-HPV (OR = 2.1; IC 95% = 1.4-3.2), smoking habits (OR = 2.2; IC 95% = 1.4-3.5), and the performance of DSI combined with colposcopy (OR = 0.6; IC 95% = 0.37-0.83) were the factors associated with the detection of H-SIL/CIN2+. A summative effect of HR-HPV and smoking habit (OR = 2.9; IC 95% = 1.7-5.0) was observed in the detection of H-SIL/CIN2+. In multivariate analysis, the presence of HPV 16/18 was the unique independent factor associated with H-SIL/CIN2+. CONCLUSION: In women carrying an ASCUS/LSIL in the Pap smear, the unique independent factor predictive of H-SIL/CIN2+ is the presence of the HPV 16/18 genotype. Smoking women carrying ASCUS/LSIL with HR-HPV should be targeted for stricter follow-up to avoid an unsuspected H-SIL/CIN2+.

Development and psychometric properties of the human papillomavirus-quality of life (HPV-QoL) questionnaire to assess the impact of HPV on women health-related-quality-of-life.

PURPOSE: The HPV-Quality-of-Life (HPV-QoL) questionnaire was developed to determine the impact of Human-Papillomavirus (HPV) infection and related interventions on women health-related quality-of-life. This study provides the development and preliminary psychometric properties of a novel HPV-QoL questionnaire for adult women with HPV. METHODS: After reviewing literature and cognitive debriefing interviews in women who had experienced HPV-related conditions, instrument items and domains were developed. A draft questionnaire was pilot tested for comprehension and ease of completion. Psychometric evaluation of the final HPV-QoL scale was conducted in a psychometric study including 252 adult women derived to our centre by a positive HPV test in the cervical cancer screening program and/or presenting genital warts. RESULTS: The present study reveals that the HPV-QoL questionnaire, structured in four domains: general well-being [including psychological well-being and social well-being subdomains], health, contagiousness and sexuality, showed good metric properties of feasibility irrespective of age or educational level, and time to administer was less than 5 min. Internal consistency and temporal stability (reliability) showed values above the acceptable standards. The instrument showed its concurrent validity by means of a significant correlation with mental and sexual existing instruments; GHQ-12 and FSFI questionnaires, respectively, and also known groups validity showing significant differences among the subgroups regarding either sexual dysfunction or mental deterioration. CONCLUSION: This study provides an HPV-QoL questionnaire with an innovative patient-reported outcomes specific measurement tool to assess HRQoL in women with HPV infection. The present study suggests this questionnaire has satisfactory psychometric properties, including validity and reliability. Results support the use of the HPV-QoL questionnaire as a HRQoL measurement instrument for daily medical practice and clinical research.

Quadrivalent Human Papillomavirus Vaccine Effectiveness after 12 Years in Madrid (Spain).

A fully government-funded human papillomavirus (HPV) vaccination program started in 2007 in Spain (only 11-14-year-old girls). The first of those vaccinated cohorts, with the quadrivalent vaccine (Gardasil), turned 25 years old in 2018, the age at which cervical cancer screening begins in Spain. The current study could provide the first evidence about the effectiveness of the quadrivalent vaccine against HPV in Spain and the influence of age of vaccination. The present ambispective cohort study, which was conducted on 790 women aged 25 and 26 years old, compares the rate of HPV prevalence and cytologic anomaly according to the vaccination status. The overall infection rate was 40.09% (vaccinated group) vs. 40.6% (non-vaccinated group). There was a significant reduction in the prevalence of HPV 6 (0% vs. 1.3%) and 16 (2.4% vs. 6.1%), and in the prevalence of cytological abnormalities linked to HPV16: Atypical Squamous Cells of Undetermined Significance (ASCUS) (2.04% vs. 14%), Low-grade Squamous Intraepithelial Lesions (LSIL) (2.94% vs. 18.7%) and High-grade Squamous Intraepithelial Lesion (HSIL) (0% vs. 40%), in the vaccinated group vs. the non-vaccinated group. Only one case of HPV11 and two cases of HPV18 were detected. The vaccine effectively reduces the prevalence of vaccine genotypes and cytological anomalies linked to these genotypes.

Effectiveness of Prophylactic Human Papillomavirus Vaccine in the Prevention of Recurrence in Women Conized for HSIL/CIN 2-3: The VENUS Study.

Background: Recent data have shown that the human papillomavirus (HPV) vaccine could impact on a decrease in high-grade cervical intraepithelial lesions (HSIL) in women who have undergone surgical treatment. This study aimed to evaluate the efficacy of human papilloma virus (HPV) vaccination against persistent/recurrent disease in patients undergoing conization for high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia-grade 2-3 (HSIL/CIN 2-3). Methods: From January 2009 to March 2019, 563 patients with HSIL/CIN 2-3 underwent conization. The population was divided into two groups according to vaccination status: vaccinated-group (V-Group) and non-vaccinated-group (NV-Group). Bivalent or quadrivalent vaccines were administered indiscriminately. A follow-up was scheduled every 6-12 months according to clinical guidelines. The mean follow-up was 29.6 vs. 36.5 months in the V-group and NV-group, respectively. Results: 277 (49.2%) women were vaccinated, while 286 (50.8%) were not. Overall, persistent/recurrent HSIL/CIN 2-3 was presented by 12/277 (4.3%) women in the V-Group and 28/286 (9.8%) in the NV-Group (HR: 0.43, 95% Confidence interval 0.22-0.84, p = 0.014). Vaccination was associated with a 57% reduction in HSIL persistence/recurrence after treatment. When no disease was present in the first 6-month follow-up visit, persistence/recurrence rates were very low in both groups: 1.1% in the V-Group vs. 1.5% in the NV-Group (p > 0.05). The factor associated with a high-risk of HSIL persistence/recurrence was the presentation of a positive co-test in the first control after treatment (p < 0.001). Conclusions: Our results corroborate the benefit of HPV vaccination in woman treated for HSIL/CIN 2-3, showing a reduction of persistent/recurrent HSIL/CIN 2-3.

Comparative pilot study about HPV test with partial genotyping in primary screening versus other strategies for cervical cancer population screening, CRYGEN 16/18 study. / Estudio piloto comparativo del test VPH con genotipado parcial en primera línea frente a otras estrategias de cribado poblacional del cáncer de cérvix. Estudio CRYGEN 16/18.

INTRODUCTION: The early detection of cervical cancer requires the implementation of molecular screening programs for human papillomavirus (HPV). However, there are discrepancies in the optimization of screening protocols. The performance of 10 primary screening strategies based on molecular, cytological or combined techniques is now evaluated. MATERIAL AND METHODS: A blind, prospective, and interventional study was designed in 1977 35-year-old women. The molecular determination was carried out by the Cobas 4800 HPV platform. Cytological analysis was performed on the same samples without knowledge of the result of the molecular assay. All women in whom HPV-16/HPV-18 was detected or presented cytological alteration together with detection of other high-risk genotypes (HPVhr) were referred to colposcopy. RESULTS: The molecular assay detected the presence of HPVhr genotypes in 12.5% of the women, while only 8.1% of the cytologies were pathological. Among the patients referred to colposcopy, in 19.5% high-grade lesions were observed, being HPV-16 present in 65.3% of them. In six of these high-grade lesions (associated with HPV-16 in all cases), cytology was reported as normal. The follow-up one year later, of women with normal cytology and HPVhr detection a HSIL/CIN2+ lesion was detected (associated to HPV-33). In the comparative study with other strategies, the protocol called CRYGEN 16/18 yielded the best balance of sensitivity and specificity with the least referral to colposcopy. CONCLUSIONS: Performing molecular detection of HPVhr with partial first-line genotyping of at least HPV-16, with direct referral to colposcopy, increases the detection rate of HSIL/CIN2+ lesions.

Vulvitis de Zoon en mujer en edad fértil. Reporte de un caso / Zoon vulvitis in a woman of childbearing age. A case report / Zoon vulvitis in a woman of childbearing age. A case report

RESUMEN La vulvitis de Zoon o vulvitis de células plasmáticas es una enfermedad inflamatoria crónica infrecuente, caracterizada por placas eritematosas bien delimitadas y brillantes que pueden afectar cualquier localización de la vulva. Suele presentarse en mujeres posmenopáusicas y plantea un difícil diagnóstico diferencial. Se insiste en la necesidad de realizar biopsia vulvar para obtener un diagnóstico histológico de certeza. Se presenta el caso de una paciente de 36 años y se comenta las opciones terapéuticas actuales descritas en la literatura.

ABSTRACT Zoon vulvitis or vulvitis circumscripta plasmacellularis is a rare chronic inflammatory disease characterized by well-delimited and shiny erythematous plaques that can affect any location of the vulva. It usually occurs in postmenopausal women and poses a difficult differential diagnosis. The need for a vulvar biopsy is emphasized to obtain a certain histological diagnosis. The case of a 36-year-old patient is presented and the current therapeutic options described in the literature are discussed.

Úlcera vulvar aguda de Lipschütz / Acute vulvar ulcer of Lipschütz

RESUMEN La úlcera de Lipschütz es una entidad poco frecuente e infradiagnosticada. Se presenta el caso de una paciente de 24 años sin antecedente de contacto sexual que consultó por aparición súbita de úlceras vulvares dolorosas, en el contexto de un cuadro pseudogripal. Se discuten los principales diagnósticos diferenciales, dado que es una enfermedad no relacionada con enfermedades de transmisión sexual y poco reconocida por los profesionales de la salud, que precisa de manejo conservador.

ABSTRACT Lipschütz ulcer is a rare underdiagnosed entity. We present the case of a 24-year-old patient without history of sexual contact who consulted for sudden occurrence of painful vulvar ulcers, in the context of flu-like symptoms. The main differential diagnoses are discussed, as it is a disease unrelated to sexually transmitted diseases and little recognized by health professionals, which requires conservative management.

Prevención primaria del virus del papiloma humano / Primary prevention of human papillomavirus

La patología relacionada con la infección por el virus del papiloma humano constituye en la actualidad un ver-dadero problema de salud pública. Si bien la primera relación causal entre el virus del papiloma humano y un cáncer fue con el cáncer de cérvix, a lo largo de los últimos años se ha podido demostrar cómo es también el agente causal de cánceres en otras localizaciones, siendo el responsable de una fracción nada despreciable de los casos de cáncer de ano, vagina, vulva, pene y orofaringe, algunos de ellos con un incremento considerable en su incidencia en los últimos años. El descubrimiento de la asociación del virus del papiloma humano con estos cánceres ha permitido el desarrollo de vacunas frente al virus del papiloma humano que sirven para la prevención primaria. Si bien en el caso del cáncer de cérvix disponemos de estrategias de prevención secundaria basadas en el cribado, no ocurre lo mis-mo con el resto de cánceres VPH-dependientes, donde la prevención solo es posible a través de estrategias de prevención primaria basadas en la vacunación. Es crucial por tanto que los profesionales sanitarios tengan un conocimiento actualizado sobre la infección por el virus del papiloma humano, la carga de enfermedad asociada y las estrategias de que disponemos para su prevención

The pathology related to human papillomavirus infection is currently a real public health problem. Although the first causal relationship between human papillomavirus and a cancer was with cervical cancer, over the last few years it has been possible to show how it is also the causative agent of cancers in other locations, being responsible for a not inconsiderable fraction of cases of cancer of the anus, vagina, vulva, penis and oropharynx, some of them with a considerable increase in their incidence in recent years. The discovery of the association of human papillomavirus with these cancers has allowed the development of vaccines against human papillomavirus that serve for primary prevention. Although in the case of cervical cancer we have secondary prevention strategies based on screening, the same is not possible for the other HPV-dependent cancers, in which prevention is only possible through primary prevention strategies based on vaccination. It is therefore essential that health professionals have up-to-date knowledge about human papillomavirus infection, the burden of associated disease and the strategies available to prevent it

Guía de cribado del cáncer de cuello de útero en España, 2014 / No disponible

No disponible

Guía de cribado del cáncer de cuello de útero en España, 2014 / No disponible

No disponible

Linfoma cervical primario: presentación de un caso y revisión de la literatura / Primary lymphoma of the uterine cervix: a case report and literature review

El linfoma primario cervical es una enfermedad muy infrecuente que se presenta clínicamente como un carcinoma de cérvix. El diagnóstico del linfoma de cérvix requiere una biopsia profunda, ya que la citología puede ser negativa. Aunque no existe consenso en el tratamiento, tradicionalmente se empleaba radioterapia. Sin embargo, últimamente se sugiere realizar tratamiento quimioterápico, pudiendo completarse con cirugía. Se presenta el caso de una paciente con linfoma cervical que requirió varias tomas de biopsia para su diagnóstico y en la que se empleó con éxito quimioterapia neoadyuvante seguida de cirugía (AU)

Primary lymphoma of the uterine cervix is extremely rare and the clinical presentation is similar to that of carcinoma of the cervix. Diagnosis is made with a deep cervical biopsy because smear tests can show false negative results. The standard treatment has not yet been established but used to be radiotherapy. Currently, combination chemotherapy is used with or without surgery. We report a case of cervical lymphoma that needed several biopsies to establish the diagnosis and was successfully treated with neoadjuvant chemotherapy and surgery (AU)

La inmunosupresión es un factor mayor de riesgo en la recidiva de las lesiones del tracto genital inferior asociadas al virus del papiloma humano / Immunosuppression is a major prognostic factor in recurrence of human papillomavirus-associated lesions of the lower genital track

Objetivo: Analizar las características de las lesiones preneoplásicas del tracto genital inferior (TGI) y los factores asociados a su recidiva. Material y métodos: Se estudió a 376 mujeres tratadas de algún tipo de neoplasia intraepitelial del TGI, en la década de los 90. Las lesiones se agruparon en cervicales y vulvares, y estas en lesiones de alto (CIN II-III o VIN) y de bajo grado (CIN I o atipia vulvar por virus del papiloma humano [AV-VPH]). El tratamiento de las CIN se realizó con asa diatérmica y para las lesiones vulvares fue la resección con bisturí frío y/o láser CO2.ResultadosLa edad media de las mujeres fue 32 años. La multicentricidad fue identificada en el 57% de las CIN y en el 87% de las lesiones vulvares. Un 10% de las mujeres en ambos grupos presentó algún tipo de inmunosupresión. Se identificó VPH de riesgo alto en el 25% de los casos. Con un seguimiento medio de 21 meses, la recidiva global de la CIN fue del 17% y la acumulada a 5 años del 47%. En las lesiones vulvares fue del 15 y el 54%, respectivamente. En ambos grupos lesionales la recidiva apareció en los primeros 3 años en más del 90% de los casos y se asoció a la inmunosupresión y el genotipo viral de riesgo alto, aunque el único factor de riesgo independiente en el análisis multivariante fue la inmunosupresión. Ninguna paciente progresó a cáncer invasor. Conclusiones: La inmunosupresión es el factor riesgo predictivo más importante de recurrencia. Las conductas orientadas a estimular la inmunidad podrían ser eficaces en prevención de la recurrencia de la enfermedad por el VPH (AU)

Objective: To analyze the characteristics of preneoplastic lesions of the lower genital tract (LGT) and the factors associated with their recurrence. Material and methods: A total of 376 women treated for some type of intraepithelial neoplasm of the LGT between 1990 and 1999 were studied. The lesions were classified into cervical intraepithelial neoplasms (CIN) and vulvar intraepithelial neoplasms (VIN) and were further classified into high-grade lesions (CIN 2-3 or VIN) and low-grade lesions (CIN 1 or human papillomavirus vulvar atypia [HPV-VA]). Treatment of cervical lesions consisted of CO2 laser and / or loop electrosurgical excision while that of vulvar lesions consisted of cold-knife local excision and / or CO2 laser. Results: The mean age of women was 32 years. Multicentric disease was found in 57% of CIN lesions and in 87% of vulvar lesions. Ten percent of women in both groups had some type of immunosuppression. High-risk HPV was identified in 25% of patients. With a mean follow-up of 21 months, the overall CIN recurrence was 17% and accumulated recurrence rate at 5 years was 47%. In vulvar lesions, these values were 15% and 54%, respectively. In both groups, more than 90% of recurrences occurred in the first 3 years, and relapse was associated with immunosuppression and high-risk viral genotype. In multivariate analysis, the only independent risk factor was immunosuppression. None of the lesions progressed to invasive cancer. Conclusions: The most important risk factor predictive of recurrence is immunosuppression. Measures to stimulate immunity could be effective in preventing HPV-related disease (AU)

Decidualización peritoneal y embolización de arterias uterinas en la hemorragia puerperal tras cesárea / Peritoneal deciduosis and uterine artery embolization in puerperal hemorrhage after cesarean section

La decidualización peritoneal es una metaplasia de células peritoneales, que aparece en la gestación por acción de la progesterona. Anatomopatológicamente, son lesiones altamente vascularizadas, por lo que es preciso el diagnóstico definitivo mediante técnicas inmunohistoquímicas para diferenciarlo de tumores malignos. La embolización arterial selectiva es una técnica conservadora para el tratamiento de las hemorragias posparto con mínimos efectos secundarios, que permite la conservación de la fertilidad. Presentamos el hallazgo de una decidualización peritoneal severa durante la realización de una cesárea en una paciente que posteriormente precisó embolización de arterias uterinas por hemorragia puerperal (AU)

Deciduosis peritonei consists of the presence of decidua in the peritoneal surface and develops during pregnancy due to the effect of progesterone. The typical lesions are highly vascularized and immunohistochemical studies are required to exclude a diagnosis of malignancy. Selective arterial embolization is a conservative procedure to treat postpartum hemorrhages with minimal side effects and allows fertility to be preserved. We present a case of severe deciduosis peritonei identified during a cesarean section in a patient who subsequently required embolization of the uterine arteries due to a postpartum hemorrhage (AU)

[Overexpression and prognostic value of p53 and HER2/neu proteins in benign ovarian tissue and in ovarian cancer]. / Grado de expresión y valor pronóstico de las proteínas p53 y HER2/neu en el tejido ovárico benigno y en el cáncer de ovario.

BACKGROUND AND OBJECTIVE: To investigate the prognostic value of p53 and HER2/neu overexpression in epithelial ovarian cancer (EOC). PATIENTS AND METHOD: p53 and HER2/neu immunostaining were performed in 198 tissue samples, 124 EOC, 44 benign ovarian tumors and 30 normal ovaries. Nuclear p53 and membranous HER2/neu immunostaining were evaluated. RESULTS: Neither p53 nor HER2/neu overexpression was seen in the benign ovarian tumors. HER2/neu immunostaining was observed in one normal ovary. P53 overexpression was found in 25% EOC and was related with advanced stage, endometrioid, clear cell and undifferentiated types, grade G3, and sub-optimal surgery. HER2/neu immunostaining was observed in 24.2% and it was associated with advanced stage, clear cell and undifferentiated types, and suboptimal surgery. Both, p53 and HER2/neu overexpression decreased overall and progression-free survival, but in the multivariant analysis, only HER2/neu overexpression was an independent prognostic factor of overall survival (RR = 2.8; 95% confidence interval [CI], 1.2-5.6) and recurrence (RR = 2.8; 95% CI, 1.1-7.1). Simultaneous p53 and HER2/neu overexpression made the prognosis worse (p < 0.01). CONCLUSIONS: HER2/neu overexpression (but not p53 overexpression) is a major prognostic factor in EOC.

Grado de expresión y valor pronóstico de las proteínas p53 y HER2/neu en el tejido ovárico benigno y en el cáncer de ovario / Overexpression and prognostic value of p53 and HER2/neu proteins in benign ovarian tissue and in ovarian cancer

Fundamento y objetivo: Determinar la expresión de las proteínas p53 y HER2/neu en el tejido ovárico y analizar su valor pronóstico en el cáncer de ovario. Pacientes y método: Se estudió a un total de 198 pacientes, 124 con cáncer epitelial de ovario (CEO), 44 con tumores benignos y 30 con ovarios normales. Se midió la expresión nuclear de p53 y en membrana de HER2/neu mediante técnicas inmunohistoquímicas. Resultados: No se observó sobreexpresión de p53 o HER2/neu en los tumores benignos de ovario. Sólo hubo sobreexpresión de HER2/neu en un ovario normal. El 25% de los casos de CEO mostró sobreexpresión de p53 y ésta se relacionó con los estadios avanzados, con los tipos histológicos endometrioides, de células claras e indiferenciados, con el grado G3 y con la citorreducción subóptima. El 24,2% de los CEO sobreexpresó HER2/neu y se relacionó con los tumores en estadio avanzado, con los tipos histológicos de células claras e indiferenciado y con una citorreducción subóptima. Tanto la sobreexpresión de p53 como la de HER2/neu se asociaron a una reducción de la supervivencia global y libre de enfermedad de las pacientes con CEO; sin embargo, en el estudio multivariable sólo la sobreexpresión de HER2/neu fue un factor independiente predictivo de menor supervivencia, tanto global (riesgo relativo [RR] = 2,8; intervalo de confianza [IC] del 95%, 1,2-5,6) como libre de enfermedad (RR = 2,8; IC del 95%, 1,1-7,1). La sobreexpresión conjunta de ambas proteínas empeoró aún más el pronóstico de estas pacientes (p < 0,01). Conclusiones: La sobreexpresión de HER2/neu es un factor pronóstico importante en el CEO, no así la sobreexpresión de p53

Background and objetive: To investigate the prognostic value of p53 and HER2/neu overexpression in epithelial ovarian cancer (EOC). Patients and method: p53 and HER2/neu immunostaining were performed in 198 tissue samples, 124 EOC, 44 benign ovarian tumors and 30 normal ovaries. Nuclear p53 and membranous HER2/neu immunostaining were evaluated. Results: Neither p53 nor HER2/neu overexpression was seen in the benign ovarian tumors. HER2/neu immunostaining was observed in one normal ovary. P53 overexpression was found in 25% EOC and was related with advanced stage, endometrioid, clear cell and undifferentiated types, grade G3, and sub-optimal surgery. HER2/neu immunostaining was observed in 24.2% and it was associated with advanced stage, clear cell and undifferentiated types, and suboptimal surgery. Both, p53 and HER2/neu overexpression decreased overall and progression-free survival, but in the multivariant analysis, only HER2/neu overexpression was an independent prognostic factor of overall survival (RR = 2.8; 95% confidence interval [CI], 1.2-5.6) and recurrence (RR = 2.8; 95% CI, 1.1-7.1). Simultaneous p53 and HER2/neu overexpression made the prognosis worse (p < 0.01). Conclusions: HER2/neu overexpression (but not p53 overexpression) is a major prognostic factor in EOC