El objetivo del presente trabajo fue evaluar las diferencias conductuales en hembras lactantes en sistema intensivo confinado en una granja de la zona norte de la provincia de Buenos Aires. Con este ...fin se realizó un etograma de 43 pautas de comportamiento, estas fueron categorizadas en tres grandes grupos: dirigidas a los lechones, dirigidas al hábitat y generales. Se evaluaron 28 hembras, 11 Landrance (L) y 17 Yorkshire (Y) durante los 28 días de lactancia. Con 3 sesiones de observaciones diarias de 20 minutos cada una, durante 5 días a la semana. Los resultados obtenidos mostraron diferencias significativas (p<0,05) en pautas dirigidas al lechón: olfatear lechón, empujar lechón y morder lechón; dirigidas al hábitat: hociquear suelo y hociquear jaula; y generales: masticar, y vulva contra jaula. Con excepción de esta última, cuya mayor frecuencia correspondió a las hembras Y, el resto de las pautas mencionadas mostró una frecuencia significativamente mayor en las hembras L. Si bien ambas razas, de aptitud mixta, son utilizadas como madres de líneas maternas, los resultados obtenidos muestran actividad diferencial. Una interpretación posible es el mecanismo por el cual intentan reducir el estrés (“coping activo” vs. “coping pasivo”). Esto pone en evidencia diferentes maneras de manejar el estrés y por ende, diferente manera de acoplar con el ambiente, lo que vuelve el factor “raza” de suma importancia a la hora de estudiar y mejorar el bienestar animal en la producción.
Introduction
Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways—one involving high‐risk human papilloma virus infection (HPV‐associated), and the other without HPV ...infection (HPV‐independent) often involving TP53 mutation. HPV‐associated VSCC generally has a better progression‐free survival than HPV‐independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC.
Material and methods
Immunohistochemistry for p53, Ki67 and p16INK4A (a surrogate marker for HPV infection) was performed on formalin‐fixed paraffin‐embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi‐square test and multivariable Cox regression model were used to investigate the association of different parameters with progression‐free survival and disease‐specific survival (DSS), and Kaplan–Meier curves were used to show the association of different parameters with survival.
Results
The results of p53 and p16INK4A immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression‐free survival (p = 0.024) after adjustment for FIGO stage. p16INK4A immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression‐free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders.
Conclusions
p53 and p16INK4A immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.
Better tools are required for personalized treatment guidance of women with vulva squamous cell carcinoma. Our results demonstrate that patients with p53‐mutations have the highest risk for recurrence and death, and those positive for HPV mRNA, have better prognosis.
Zusammenfassung
Anogenitale und oropharyngeale Infektionen mit humanen Papillomviren (HPV) sind weit verbreitet. Im Fall einer klinisch manifesten Erkrankung ist die HPV‐Infektion mitunter mit ...erheblichen Auswirkungen auf die Lebensqualität assoziiert, die Behandlung geht mit einer hohen Rezidivrate einher und invasive Neoplasien (zum Beispiel Zervix‐, Anal‐, Vulva‐, Penis‐, Oropharynxkarzinom) sind zudem durch eine signifikante Morbidität und Mortalität gekennzeichnet. Die Impfung gegen HPV ist eine effektive und sichere Maßnahme zur Primärprävention HPV‐assoziierter Läsionen, allerdings sind die HPV‐Impfraten in Deutschland nach wie vor niedrig. Die vorliegende Publikation ist eine gekürzte Fassung der auf den Seiten der AWMF verfügbaren Langfassung der evidenz‐ und konsensbasierten Leitlinie „Impfprävention HPV‐assoziierter Neoplasien“. Auf der Grundlage eines systematischen Reviews mit Metaanalysen wurden von einem repräsentativen Gremium erstellte und formell konsentierte Empfehlungen zur Vakzinierung verschiedener Alters‐ und Personengruppen erarbeitet. Darüber hinaus wurden konsensbasierte Empfehlungen zu spezifischen, im Praxisalltag relevanten Fragestellungen bezüglich besonderer Situationen erstellt. Diese sollen in einem Themenfeld, in dem vielfach Unsicherheiten bestehen und sowohl Patientinnen und Patienten als auch Gesundheitsdienstleisterinnen und ‐dienstleister teils mit kontroversen und emotional aufgeladenen Standpunkten konfrontiert sind, auf Grundlage der aktuell vorliegenden Studienlage und eines repräsentativen Expertenkonsenses Orientierung und Sicherheit bieten.
El fibroadenoma es una neoplasia benigna usualmente localizada en mama. Su localización vulvar es extremadamente rara, con publicación de pocos casos. Su origen es incierto y muy debatible, en tanto ...se piensa que puede originarse de un tejido mamario ectópico vulvar o de glándulas anogenitales similares a las de tejido mamario que existen normalmente. Se presenta un caso inusual de fibroadenoma vulvar en una mujer de 29 años que durante dos años evidenció tumoración a nivel de la vulva que le producía dispareunia y sangrado poscoital. A nivel del labio mayor de la vulva se extirpó un tumor bien delimitado de 3 x 2 x 2 cm, blanquecino, de consistencia firme. En la microscopia se observó un fibroadenoma que por inmunohistoquímica mostró positividad para receptores de estrógeno y progesterona.
The expression of the cyclin-dependent kinase inhibitor p16 correlates with the presence of human papillomavirus. The purpose of this investigation was to assess the prognostic relevance of p16 ...expression in patients with vulvar squamous cell carcinoma (VSCC) treated with radical surgery followed by adjuvant (chemo) radiation in selected cases.
Seventy-eight patients were analyzed retrospectively.
Positive p16 immunostaining was detected in 19 (24.4%) patients. Five-year disease-free survival (DFS) and 5-year overall survival (OS) were better in p16-positive compared to p16-negative patients (83.9% versus 37.3% p=0.002 and 91.7% versus 57.6%, p=0.003, respectively). p16 expression retained prognostic relevance at multivariate analysis for both DFS and OS.
p16 expression was detected in 24.4% of patients with VSCC and was found to be an independent prognostic variable for both DFS and OS.
There is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based on p16 and p53 ...immunohistochemistry (IHC) as surrogate markers for HPV and TP53 mutations.
A large retrospective cohort of surgically treated women with primary VSCC was used. VSCC were classified into three subtypes: HPV-positive (HPVpos), HPV-negative/p53 mutant (HPVneg/p53mut), and HPV-negative/p53 wildtype (HPVneg/p53wt). Overall survival (OS), relative survival (RS), and recurrence-free period (RFP) were depicted using the Kaplan-Meier method and survival curves for relative survival; associations were studied using univariable and multivariable Cox proportional hazard models.
Of the 413 VSCCs, 75 (18%) were HPVpos, 63 (15%) HPVneg/p53wt, and 275 (66%) HPVneg/p53mut VSCC. Patients with HPVneg/p53mut VSCC had worse OS and RS (HR 3.43, 95%CI 1.80–6.53, and relative excess risk (RER) of 4.02; 95%CI 1.48–10.90, respectively, and worse RFP (HR 3.76, 95%CI 2.02–7.00). HPVpos VSCC patients showed most favorable outcomes. In univariate analysis, the molecular subtype of VSCC was a prognostic marker for OS, RS and RFP (p = 0.003, p = 0.009, p < 0.001, respectively) and remained prognostic for RFP even after adjusting for known risk factors (p = 0.0002).
Stratification of VSCC by p16- and p53-IHC has potential to be used routinely in diagnostic pathology. It results in the identification of three clinically distinct subtypes and may be used to guide treatment and follow-up, and in stratifying patients in future clinical trials.
•Management of women with vulvar squamous cell carcinoma (VSCC) presents clinical challenges, impacting quality of life.•Better tools are needed for individual risk assessment and treatment guidance.•Classification of VSCC based on p16- and p53-immunohistochemistry identifies three prognostic distinct subtypes.•HPVpos VSCC have best clinical outcome, and HPVneg/p53 mutant VSCC have highest risk for death and recurrence.
Vulvar squamous cell carcinomas and their precursors are currently classified by the World Health Organization based on their association with high-risk human papillomavirus (HPV). HPV independent ...lesions often harbor driver alterations in TP53, usually seen in the setting of chronic vulvar inflammation. However, a group of pre-invasive vulvar squamous lesions is independent from both HPV and mutant TP53. The lesions described within this category feature marked acanthosis, verruciform growth and altered squamous maturation, and over the last two decades several studies have added to their characterization. They have a documented association with verrucous carcinoma and conventional squamous cell carcinoma of the vulva, suggesting a precursor role. They also harbor recurrent genomic alterations in several oncogenes, mainly PIK3CA and HRAS, indicating a neoplastic nature. In this review, we provide a historical perspective and a comprehensive description of these lesions. We also offer an appraisal of the terminology used over the years, going from Vulvar Acanthosis with Altered Differentiation and Verruciform Lichen Simplex Chronicus to Differentiated Exophytic Vulvar Intraepithelial Lesion and Vulvar Aberrant Maturation, the latter term having been recently proposed by the International Society for the Study of Vulvovaginal Diseases. In line with the recognition of these lesions by the 2020 World Health Organization Classification of Tumours as a neoplastic precursor, we herein propose the term HPV-independent, p53-wild-type verruciform acanthotic Vulvar Intraepithelial Neoplasia (HPVi(p53wt) vaVIN), which better conveys not only the pathology but also the neoplastic nature and the biologic risk inherent to these uncommon and challenging lesions. We outline strict morphologic and immunohistochemical criteria for its diagnosis and distinction from mimickers. Immunohistochemistry for p16 and p53 should be performed routinely in the diagnostic work-up of these lesions, and the morphologic alternative term vaVIN should be reserved for instances in which p16/HPV/p53 status is unknown. We also discuss management considerations and the need to further explore precursors within and beyond the spectrum of verruciform acanthotic vulvar intraepithelial neoplasia.
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