Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity

Immunohistochemical analysis of E-cadherin has changed the way lobular neoplasia is perceived. It has helped to classify difficult cases of carcinoma in situ with indeterminate features and led to the identification of new variants of lobular carcinoma. Pleomorphic lobular carcinoma (PLC) and pleomorphic lobular carcinoma in situ (PLCIS), recently described variants of invasive and in situ classic lobular carcinoma, are reported to be associated with more aggressive clinical behaviour. Although PLC/PLCIS show morphological features of classic lobular neoplasia and lack E-cadherin expression, it is still unclear whether these lesions evolve through the same genetic pathway as lobular carcinomas or are high-grade ductal neoplasms that have lost E-cadherin. Here we have analysed a case of extensive PLCIS and invasive PLC associated with areas of E-cadherin-negative carcinoma in situ with indeterminate features, using immunohistochemistry, chromogenic in situ hybridization, high-resolution comparative genomic hybridization (CGH) and array-based CGH. We observed that all lesions lacked E-cadherin and beta-catenin and showed gain of 1q and loss of 16q, features that are typical of lobular carcinomas but are not seen in high-grade ductal lesions. In addition, amplifications of c-myc and HER2 were detected in the pleomorphic components, which may account for the high-grade features in this case and the reported aggressive clinical behaviour of these lesions. Taken together, these data suggest that at least some PLCs may evolve from the same precursor or through the same genetic pathway as classic lobular carcinomas. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Bile-salt-induced aggregation of poly(N-isopropylacrylamide) and lowering of the lower critical solution temperature in aqueous solutions

The effect of sodium cholate (NaC; concentration 1-16 mM), a biological surfactant, on the aggregation behavior of 1% (w/v, 2.2 × 10(-3) M) poly(N-isopropylacrylamide) (PNIPAM) aqueous solutions was studied as a function of temperature. From turbidity, dynamic light scattering, viscosity, and fluorescence measurements, it was observed that (i) there is NaC-induced nanoscale aggregation of PNIPAM in its sol state and (ii) the lower critical solution temperature corresponding to sol-gel transition shifts to a lower temperature by about 2 °C.

A lumped parameter model for the analysis of the motion of the muscles of the lower limbs under whole-body vibration

Through a lumped parameter modelling approach, a dynamical model, which can reproduce the motion of the muscles of a human body standing in different postures during Whole Body Vibrations (WBVs) treatment, has been developed. The key parameters, associated to the dynamics of the motion of the muscles of the lower limbs, have been identified starting from accelerometer measurements. The developed model can be usefully applied to the optimization of WBVs treatments which can effectively enhance muscle activation. © 2013 IEEE.

Population viability analyses of Chamaecrista keyensis (Leguminosae: Caesalpinioideae), a narrowly endemic herb of the lower Florida Keys: Effects of seasonal timing of fires and the urban -wildland interface

This research first evaluated the effects of urban wildland interface on reproductive biology of the Big Pine Partridge Pea, Chamaecrista keyensis, an understory herb that is endemic to Big Pine Key, Florida. I found that C. keyensis was self-compatible, but depended on bees for seed set. Furthermore, individuals of C. keyensis in urban habitats suffered higher seed predation and therefore set fewer seeds than forest interior plants. ^ I then focused on the effects of fire at different times of the year, summer (wet) and winter (dry), on the population dynamics and population viability of C. keyensis. I found that C. keyensis population recovered faster after winter burns and early summer burns (May–June) than after late summer burns (July–September) due to better survival and seedling recruitment following former fires. Fire intensity had positive effects on reproduction of C. keyensis. In contrast, no significant fire intensity effects were found on survival, growth, and seedling recruitment. This indicated that better survival and seedling recruitment following winter and early summer burns (compared with late summer burns) were due to the reproductive phenology of the plant in relation to fires rather than differences in fire intensity. Deterministic population modeling showed that time since fire significantly affected the finite population growth rates (λ). Particularly, recently burned plots had the largest λ. In addition, effects of timing of fires on λ were most pronounced the year of burn, but not the subsequent years. The elasticity analyses suggested that maximizing survival is an effective way to minimize the reduction in finite population growth rate the year of burn. Early summer fires or dry-season fires may achieve this objective. Finally, stochastic simulations indicated that the C. keyensis population had lower extinction risk and population decline probability if burned in the winter than in the late summer. A fire frequency of approximately 7 years would create the lowest extinction probability for C. keyensis. A fire management regime including a wide range of burning seasons may be essential for the continued existence of C. keyensis and other endemic species of pine rockland on Big Pine Key. ^

Expressão imuno-histoquímica do ativador de plasminogênio do tipo uroquinase e seu receptor em carcinoma epidermoide de língua oral e sua relação com parâmetros clínico-patológicos

Squamous cell carcinoma (SCC ) is the most common malignancy of the oral cavity (OSCC), with a high mortality rate. Due to this, the discovery of biomarkers that facilitate the understanding of the biological behavior of the tumor and improve treatment is necessary. Urokinase type plasminogen activator (uPA) and its receptor, uPAR, are responsible for the proteolysis of structures of the basement membrana and extracellular matrix, facilitating tumor invasion. This study aims to assess the immuno expression of these proteins in 46 cases of squamous cell carcinoma of the oral tongue (OTSCC). These results were related to the presence of metastasis, clinical TNM staging, locoregional recurrence, outcome of the lesion and histological grading. Immunostaining of each case was evaluated semiquantitatively, in the front of invasion and center of the tumor, in which scores were assigned: 0 (0% of positive cells), 1 (1-10% of positive cells), 2 (11 -50% positive cells) and 3 (more than 50% positive cells). The expression of uPA was observed in 93.5% (n=43) of the cases in the front of invasion, with predominance of score 2 (n=16; 34.8%) and in 67.9% (n=31) of the cases in the center of the tumor, with predominance of score 1 (n=15; 32.6%). Overall, the immunoexpression of uPA was not associated with clinical parameters. Regarding the malignant histological grading, a higher expression of uPA was observed in cases of high-grade malignancy comp ared to low-grade malignancy (p=0.05). Regarding the morphological parameters, increased expression of uPA was observed in the worst mode of invasion (p=0.03 ). The expression of uPAR was observed in 73.9% of cases in the front of invasion, with a predominance of score 1 (n=21; 45.6 %), and in 47.5% (n=21) of the cases in the center of the tumor, with a predominance of score 0 (n=25; 54.4%). Although no statistical differences were observed in relation to lymph node metastasis, clinical TNM staging, outcome, and histological grading, there was a higher expression of uPAR in cases with locoregional recurrence (p=0.04). Regarding the tumor intra -localization, it was observed an increased expression of uPA and uPAR at the front of invasion in relation to the center of the tumor (p<0.001). Regarding the correlation between uPA and uPAR, there was no statistical sign ificance. Based on these results, it is suggested that uPA and uPAR are involved in the progression of CELO, mainly in the deeper region of the tumor.

Expressão imuno-histoquímica do ativador de plasminogênio do tipo uroquinase e seu receptor em carcinoma epidermoide de língua oral e sua relação com parâmetros clínico-patológicos

Squamous cell carcinoma (SCC ) is the most common malignancy of the oral cavity (OSCC), with a high mortality rate. Due to this, the discovery of biomarkers that facilitate the understanding of the biological behavior of the tumor and improve treatment is necessary. Urokinase type plasminogen activator (uPA) and its receptor, uPAR, are responsible for the proteolysis of structures of the basement membrana and extracellular matrix, facilitating tumor invasion. This study aims to assess the immuno expression of these proteins in 46 cases of squamous cell carcinoma of the oral tongue (OTSCC). These results were related to the presence of metastasis, clinical TNM staging, locoregional recurrence, outcome of the lesion and histological grading. Immunostaining of each case was evaluated semiquantitatively, in the front of invasion and center of the tumor, in which scores were assigned: 0 (0% of positive cells), 1 (1-10% of positive cells), 2 (11 -50% positive cells) and 3 (more than 50% positive cells). The expression of uPA was observed in 93.5% (n=43) of the cases in the front of invasion, with predominance of score 2 (n=16; 34.8%) and in 67.9% (n=31) of the cases in the center of the tumor, with predominance of score 1 (n=15; 32.6%). Overall, the immunoexpression of uPA was not associated with clinical parameters. Regarding the malignant histological grading, a higher expression of uPA was observed in cases of high-grade malignancy comp ared to low-grade malignancy (p=0.05). Regarding the morphological parameters, increased expression of uPA was observed in the worst mode of invasion (p=0.03 ). The expression of uPAR was observed in 73.9% of cases in the front of invasion, with a predominance of score 1 (n=21; 45.6 %), and in 47.5% (n=21) of the cases in the center of the tumor, with a predominance of score 0 (n=25; 54.4%). Although no statistical differences were observed in relation to lymph node metastasis, clinical TNM staging, outcome, and histological grading, there was a higher expression of uPAR in cases with locoregional recurrence (p=0.04). Regarding the tumor intra -localization, it was observed an increased expression of uPA and uPAR at the front of invasion in relation to the center of the tumor (p<0.001). Regarding the correlation between uPA and uPAR, there was no statistical sign ificance. Based on these results, it is suggested that uPA and uPAR are involved in the progression of CELO, mainly in the deeper region of the tumor.

Resilience and the cultural landscape : the case of the Lower Ninth Ward after Hurricane Katrina

Le but de cette recherche est d’évaluer l’importance du paysage culturel dans la résilience des communautés urbaines post-catastrophes. Ce travail se concentre sur le quartier du Lower Ninth Ward dans la ville de La Nouvelle-Orléans (États-Unis) après le passage de l’ouragan Katrina en 2005. Les catastrophes naturelles prennent une envergure et causent des dommages considérables lorsqu’elles touchent des villes. La reconstruction post -désastre est donc très dispendieuse pour les villes et les gouvernements, d’autant que certaines régions sont dévastées au point qu’elles doivent être reconstruites au complet. Cependant, le coût le plus lourd à assumer reste celui en vies humaines et si rebâtir les éléments concrets d’une ville est une tâche difficile à entreprendre, reconstruire une communauté est considérablement plus complexe. Dans le but de comprendre une telle démarche, cette recherche se concentre sur les éléments intangibles, comme l’attachement au lieu et les réseaux sociaux, dont une communauté a besoin pour se reconstituer de façon durable et résiliente. Le concept de résilience est très contesté dans la littérature et plusieurs chercheurs se sont essayés à le mesurer. Cette recherche adopte une perspective critique sur le concept et le revisite d’un point de vue holistique pour mettre en lumière sa complexité. Cette démarche permet de remettre en question l’importance de mesurer un concept finalement en perpétuelle redéfinition dans le temps et selon les échelles géographiques. De plus, en établissant une relation entre résilience et paysage culturel, il a été possible de mieux comprendre la complexité de la résilience. Touchant à plusieurs disciplines (architecture de paysage, urbanisme et sociologie), cette recherche utilise une méthodologie qui reflète son aspect multidisciplinaire : les méthodes mixtes. Ces dernières permettent la collecte de données quantitatives et qualitatives qui produisent une vue globale de la situation post-Katrina à travers le regroupement de recensions statistiques, d’observations de terrain et d’articles de journaux. Parallèlement, des entretiens ont été réalisés avec des résidents du quartier ainsi qu’avec des professionnels pour mieux comprendre les différents points de vue. Cette méthodologie a permis de produire des résultats au niveau du cas d’étude autant qu’au niveau théorique. La recherche valide l’importance de prendre en compte le paysage culturel dans les situations post-catastrophes, (en particulier) dans la mesure où il s’agit d’un élément souvent négligé par les urbanistes et les acteurs locaux. En effet, les éléments constitutifs du paysage culturel tels que l’attachement au lieu et les réseaux sociaux, participent d’un sentiment d'appartenance (« home ») et d’une volonté, pour les résidents, de reconstruire leurs habitations, leur communauté ainsi que leur quartier. Toutefois, il faut reconnaître que ces éléments ne suffisent pas à retrouver ce qu’ils ont perdu. Ainsi, l’étude du paysage culturel permet non seulement de mieux comprendre la complexité de la résilience, mais démontre également que cette dernière est une construction sociale.

Eosinophilia is a favourable prognostic marker in oral squamous cell carcinoma

Suusyöpä on yleisin pään ja kaulan alueen pahanlaatuisista kasvaimista. Niistä yli 90 % on levyepiteelikarsinoomia. Koska suusyöpäpotilaan viisivuotisennuste on vain noin 50 %, on jatkuva tarve löytää keinoja ennustamaan potilaan selviytymistä ja ohjaamaan hoitoa. Suun levyepiteelikarsinooman ympäristössä havaitaan säännöllisesti eosinofiilejä. Eosinofiili on ihmisen immuunijärjestelmän erikoistunut solu, joiden määrä lisääntyy sekä tulehdusreaktioissa että syöpien läheisyydessä. Toistaiseksi ei tiedetä, miten eosinofiilit liittyvät suun levyepiteelikarsinoomaan, mutta oletuksena on, että suusyöpään liittyvällä eosinofilialla, TATE (tumor-associated tissue eosinophilia), voisi olla vaikutusta suun levyepiteelikarsinoomapotilaan ennusteeseen. Tämän tutkimuksen tarkoituksena oli selvittää TATE:n ilmenemistä ja vaikutusta potilaan ennusteeseen suun levyepiteelikarsinoomassa. Lisäksi tutkimus käsittelee potilaan ennusteen kannalta optimaalista eosinofiilimäärän raja-arvoa, jota voitaisiin käyttää patologin työkaluna ennusteen arvioinnissa. Tutkimusaineisto koostui Turun yliopiston Suupatologian laitoksella vuosina 2002-2010 tutkituista 122 suuontelon ja huulen limakalvokoepalasta, jotka oli otettu diagnostisia tarkoituksia varten 99 potilaalta. Tutkimuksen potilaista 44 oli naisia ja 55 miehiä, ja heidän keski-ikänsä oli 65,3 vuotta. Seuranta-aika oli keskimäärin 40,7 kk. Kaksi tutkijaa analysoivat hematoksyliini-eosiinilla värjätyt näytteet suurentamalla ne 400-kertaisiksi valomikroskoopilla. Eosinofiilien määrä laskettiin yhteensä kuudelta edustavimmalta syövän ja strooman alueelta. TATE:n suhde potilaan kliinispatologisiin piirteisiin ja selviytymiseen selvitettiin Turun yliopistollisen keskussairaalan potilastiedoistoista ja analysoitiin tilastollisesti käyttämällä Fischerin testiä. Työllä oli Varsinais-Suomen sairaanhoitopiirin eettisen toimikunnan lupa (nro T10/2011, päätös O31/11). Levyepiteelikarsinooman kliininen kuva vaihteli haavaisen muutoksen ollessa yleisin. Yleisin sijainti levyepiteelikarsinoomalle oli kieli. TATE:a löydettiin 61,5 %:sta (78/122) levyepiteelikarsinoomanäytteitä. Mikäli TATE:a ei löydetty tai sen määrä oli korkea, oli potilaan selviytyminen tilastollisesti merkitsevästi parempi kuin potilailla, joilla TATE oli matala. Lisäanalyyseissä havaittiin, että potilaan ennuste oli tilastollisesti merkitsevästi huonompi, mikäli TATE:n raja-arvo oli vähemmän kuin neljä eosinofiiliä per tutkittu mikroskooppinäkymä (HPF). TATE on täten merkki suun levyepiteelikarsinoomapotilaan paremmasta ennusteesta erityisesti, kun havaitaan enemmän kuin neljä eosinofiiliä/HPF. Tutkimustulosten varmistamiseksi tarvitaan kuitenkin jatkossa laajempia tutkimuksia.