Spontaneous feline mammary intraepithelial lesions as a model for human estrogen receptor- and progesterone receptor-negative breast lesions

Background. Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women. Methods. Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues. Results. Intraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs. Conclusion. The remarkable similarity of feline mammary IELs to those of humans, with the tendency to lose hormone receptor expression in atypical IELs, supports the cat as a possible model to study ER- and PR-negative breast lesions

ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC.POCI/CVT/62940/2004 and by the PhD grants (SFRH/BD/23406/2005 and SFRH/BD/31754/2006, of the Science and Technology Foundation (FCT) from Portugal

Transformation of local lives through volunteer tourism: Thai and Peruvian case studies

Volunteer tourism, because of its ambiguities and complexities, represents an interesting and controversial field of investigation. However, to date few empirical studies have been conducted on its transformative potential for the host populations. The literature on volunteer tourism focuses mainly on the volunteers, their motivations, expectations and the transformations they go through during volunteer tourism (Zahra and McGehee, 2013). This chapter aims at bridging the gap in the literature and addressing the potential of volunteer tourism to shape and transform host communities’ perceptions and behaviours. Through a comparative study of two popular volunteer tourism destinations in Peru and Thailand, the transformative process of the hosting population is investigated. It is argued that residents, in experiencing volunteer tourism and encountering volunteers, are active agents of change within the socio-cultural environments they inhabit. Further, in an attempt to understand hosts ‘as persons and how they encounter, receive, respond and react to the effective change in conditions which tourism ultimately entails’ (Robinson, 2012, p. 23), the authors reflect on the long-term social transformations that volunteer tourism brings to host communities. The concept of personal transformation and, in particular, hosts’ learning and personal development is explored

REPRODUCIBILITY AND FEASIBILITY OF CLASSIFICATION AND NATIONAL GUIDELINES FOR HISTOLOGICAL DIAGNOSIS OF CANINE MAMMARY GLAND LESIONS: A MULTI-INSTITUTIONAL RING STUDY.

A standardised histological diagnosis provides the basis for clinical treatment and management decisions but also contributes to monitoring cancer incidence, using cancer epidemiology to enlighten the causes of the disease, and framing the activity of cancer research. However, the accuracy of histological diagnosis is inadequately understood in veterinary oncology and often lacks standardisation and includes misleading terminology, causing variable/personal interpretation of histological criteria and resulting in non-uniform diagnosis and impossibility to compare studies and interchange data. The aim of the present work was to quantify interobserver agreement of canine mammary tumours (CMTs) among pathologists with different diagnostic experiences and belonging to different institutions when the same classification (including application of ICD-O codes), grading systems, and guidelines were applied. A group of 15 pathologists reviewed the recently published Davis-Thompson Foundation classification for mammary lesions, identified critical points and agreed on guidelines to overcome these points. The guidelines were applied in a blinded ring test on 36 CMTs. The interobserver agreement, feasibility, and reproducibility of guidelines, were statistically assessed by Kappa analysis. The overall concordance rate of diagnostic interpretations of participating pathologists expressed in terms of identification of Hyperplasia-Dysplasia vs Benign vs Malignant lesions showed a substantial agreement (average k ranging from 0.66 to 0.82, with a k-combined of 0.76). Instead, outcomes expressed in terms of ICD-O morphological code/diagnosis of histotype had only a moderate agreement (average k ranging from 0.44 and 0.64, with a k combined of 0.54). Results were encouraging, demonstrating that internationally established classifications and consensus panel guidelines can produce moderate to substantial agreement, however additional efforts are needed to further reduce interobserver variability in CMTs diagnosis, grading and classification

STANDARDIZATION INITIATIVE FOR CANINE MAMMARY TUMOURS: NATIONAL GUIDELINES, MULTI-INSTITUTIONAL RING TEST AND DIAGNOSTIC ALGORITHM

Introduction: Standardization of histological diagnosis is a matter of debate both in human and veterinary medicine, particularly for heterogeneous lesions such as canine mammary tumours (CMTs). Classification of CMTs has evolved over time; however, the accuracy of histological diagnosis is inadequately understood and often includes misleading terminology and variable/personal interpretation resulting in non-uniform diagnosis and impossibility to compare studies and interchange data. As an initiative of the Italian Association of Veterinary Pathology (AIPVET), a panel of 15 veterinary pathologists was formed with the aim to i) discuss the last Davis-Thompson DVM Foundation CMTs classification and develop guidelines for its application, ii) quantify interobserver diagnostic agreement, and iii) develop a graphic diagnostic algorithm. Materials and methods: The panel performed 25 meetings, identified critical points of CMT classification and agreed on consensus guidelines, arranged a blinded ring test on 36 CMTs and discussed the structure of a diagnostic algorithm. Results: Critical points were discussed and precise guidelines were elaborated including a consensus on robust prognostic markers and content of the histopathological report. Overall concordance rate (kappa analysis) of diagnostic interpretations showed substantial and moderate agreement, respectively, for identification of hyperplasia-dysplasia vs benign vs malignant lesions and morphological diagnosis of histotype. A diagnostic algorithm was produced to be tested for efficacy in further studies. Conclusions: Consensus guidelines can help standardization, producing moderate to substantial agreement; however, additional efforts such as development of easy to apply algorithms are needed to further reduce interobserver variability in CMT classification

Analisi sulle difformità dei percorsi formativi degli specializzandi di Igiene e Medicina Preventiva in Italia: le scuole di specializzazione sono in grado di formare pienamente gli specialisti in Sanità Pubblica del futuro?

Introduzione Il percorso formativo dello specialista in Igiene e Medicina Preventiva dovrebbe garantire adeguate conoscenze tecnico-scientifiche e professionali nei campi della medicina preventiva, della promozione della salute e della programmazione dei servizi sanitari secondo quanto indicato anche dal DM 285/2005. La Consulta degli Specializzandi, da sempre coinvolta in attività di monitoraggio della formazione a livello nazionale, si prefigge l'obiettivo di valutare l'omogeneità delle proposte formative tra le diverse sedi italiane, non solo per segnalare le criticità, ma anche per evidenziarne le opportunità. Materiali e Metodi Lo studio, di tipo cross-sectional, è stato condotto mediante la somministrazione di un questionario semi-strutturato inviato per la compilazione ai rappresentanti di tutte le Scuole di Igiene e Medicina Preventiva italiane. Lo strumento di valutazione è costituito da quattro sezioni: informazioni generali, attività formativa universitaria, attività formativa extra-universitaria, attività formativa intersettoriale. L'indagine è stata svolta nel periodo tra marzo e maggio 2013 ed è stata prodotta un'analisi descrittiva dei dati ottenuti. Risultati Il questionario è stato compilato da 28 Scuole su 33, distribuite su tutto il territorio nazionale. Il numero di iscritti varia tra 7 e 31 e il rapporto tra docenti del settore scientifico-disciplinare e medici in formazione è compreso tra 0,2 e 2. Per quanto riguarda la didattica, solo in 4 Scuole si effettuano tutti i corsi previsti dal DM. La maggior parte delle sedi svolge almeno il 75% dei corsi previsti, ma esistono sedi in cui il numero di corsi è inferiore al 50%. La maggior parte delle Scuole svolge più del 60% delle attività professionalizzanti essenziali secondo il decreto, ma 2 Scuole non arrivano al 50%. Tutte le Scuole prevedono un tirocinio di 6-12 mesi in ASL, per affiancare principalmente le attività del Dipartimento di Prevenzione. Ovunque è previsto un periodo in Direzione Medica Ospedaliera, mentre le Strutture Riabilitative rientrano raramente nella rete formativa. Nella maggioranza delle Scuole è possibile frequentare aziende con rischio biologico oppure seguire simili attività nei Servizi dedicati della ASL. Molte Scuole, infine, consentono di frequentare diverse strutture territoriali (Agenzia di Controllo delle Acque), regionali (Assessorati) o statali (Ministero, Istituto Superiore di Sanità); in alcuni casi si tratta di Università gemellate e Istituti di Ricerca. Discussione La maggior parte delle Scuole di Specializzazione italiane prevedono lo svolgimento della quasi totalità delle attività formative previste, ma l'organizzazione risulta estremamente eterogenea. In generale emerge una certa flessibilità relativamente alle strutture che gli specializzandi possono frequentare e ai tempi di permanenza, essendo sufficienti nella maggior parte dei casi gli accordi con i tutor. D'altra parte, l'assenza di un tirocinio strutturato non solo costituisce un punto di difformità tra le diverse Scuole, ma rischia di creare diseguaglianze tra specializzandi di una stessa Scuola. Infine, considerato che gli item valutati indagavano aree chiave della formazione, va notato che in alcune sedi non viene effettuata neanche la metà delle attività didattiche e pratiche. La Consulta degli Specializzandi continuerà il monitoraggio della formazione, ponendo particolare attenzione alle possibili discrepanze tra i piani didattici delle Scuole e quanto effettivamente svolto da ogni singolo specializzando