The value of Phosphohistone H3 as a cell proliferation marker in oral squamouscell carcinoma. A comparative study with Ki-67 and the mitotic activity index

Background: The Phosphohistone H3 (PHH3) antibody is recognized as a biomarker of cell proliferation, specificfor cells in mitosis, of prognostic value in different malignant neoplasms, however it has been poorly studied inoral squamous cell carcinoma (OSCC). The main objective of this study was to evaluate the immunoexpression ofthe PHH3 in the OSCC, through the correlation with the immunoexpression of Ki-67, the mitotic activity index(MAI), histological grading, clinical-morphological parameters and the rate of survival.Material and Methods: The study sample consisted of 62 cases of OSCC diagnosed in the Pathological AnatomyLaboratory of the Faculty of Dentistry, University of the Republic (Uruguay). In each of them, an immunohistochemical technique was performed for Ki-67 and PHH3 (serine 10) antibodies. Image J software was used for theMAI and biomarker quantification, defining the percentage of positivity and mitotic figures per 1000 tumor cells.Results: a significant association was obtained between the expression of PHH3 (p 0.016) and MAI (p 0.031) withsurvival time. However, no similar relationship was found with Ki-67 (p 0.295). Although it was confirmed astatistical association between histological grade and Ki-67 immunoexpression (p 0.004), PHH3 did not show asimilar relationship (p 0.564).Conclusions: It was confirmed the role of the PHH3 antibody as a biomarker of mitotic figures in OSCC and as apotential marker of cell proliferation. It is noteworthy that this is one of the first works that evaluates a possiblerelationship between the expression of this antibody and survival in OSCC. (AU)

Perfil inmunohistoquímico del mixoma odontogénico, con énfasis en marcadores de agresividad tumoral y microdensidad vascular / Perfil imuno-histoquímico do mixoma odontogênico, com ênfase em marcadores de agressividade tumoral e microdensidade vascular / Immunohistochemical profile of odontogenic myxoma, with a focus on microvascular density and tumor aggressiveness markers

Con el fin de tener una mayor comprensión sobre el comportamiento biológico del mixoma odontogénico (MO), se realizó inmunohistoquímica en 31 muestras, utilizando marcadores relacionados con mecanismos de progresión tumoral (adhesión, angiogénesis, apoptosis, inflamación y proliferación celular). El epitelio odontogénico fue detectado en cuatro muestras mediante CK19 y CD138, este último, mostró expresión baja en matriz extracelular (MEC) y alta en las células tumorales. La microdensidad vascular (MDV) media fue de 7.51 y 5.35 vasos marcados con CD34 y VEGF-A respectivamente. Una alta expresión de Orosomucoide-1 y Mast Cell Tryptase se observó células tumorales y en MEC. El MO mostró negatividad para Calretinina. Este perfil inmunohistoquímico, la baja expresión para Ki-67, Bcl-2 y p53, y la relativamente baja MDV, sugieren que la actividad proliferativa, anti-apoptótica o angiogénica no representan los principales mecanismos de crecimiento del MO, los cuales podrían estar asociados a eventos como inmunomodulación y degradación de la MEC.

Immunohistochemistry tests were performed in 31 samples to elucidate the biological behavior of the odontogenic myxoma (OM), using markers related to mechanisms of tumor progression (adhesion, angiogenesis, apoptosis, inflammation and cell proliferation). Odontogenic epithelium was detected in four samples with CK19 and CD138; the latter had a low expression in the extracellular matrix (ECM) and a high expression in tumor cells. The mean microvascular density (MVD), assessed with CD34 and VEGF-A, was 7.51 and 5.35 blood vessels. A high expression of orosomucoid-1 and mast cell tryptase was observed in tumor cells and ECM, while calretinin was negative. The immunohistochemical profile mentioned above, as well as the low expression of Ki67, Bcl-2 and p53 and the relatively low MVD, suggest that the proliferative, antiapoptotic and angiogenic activities do not represent the main growing mechanisms of OM, which could be associated to other events, such as immunomodulation and ECM degradation.

Para melhor compreensão do comportamento biológico do mixoma odontogênico (MO), imuno-histoquímica foi realizada em 31 amostras, utilizando marcadores relacionados aos mecanismos de progressão tumoral (adesão, angiogênese, apoptose, inflamação e proliferação celular). Epitélio odontogênico foi detectado em quatro amostras por CK19 e CD138, o último mostrou baixa expressão na matriz extracelular (MEC) e alta em células tumorais. A microdensidade vascular (MDV) média foi de 7.51 e 5.35 vasos marcados com CD34 e VEGF-A, respectivamente. Uma alta expressão de Orosomucoide-1 e Mast Cell Tryptase foi observada nas células tumorais e na MEC. O MO mostrou negatividade para Calretinina. O perfil imuno-histoquímico mencionado acima, a baixa expressão de Ki-67, Bcl-2 e p53 e a relativamente baixa MDV, sugerem que a atividade proliferativa, anti-apoptótica ou angiogênica não representam os principais mecanismos de crescimento do MO, os quais poderiam estar associados com eventos como imunomodulação e degradação da MEC.

Estudio de la proliferación celular en gérmenes dentarios humanos / Cell proliferation study in human tooth germs

El objetivo de este estudio fue conocer la expresión de MCM4-5-6 en gérmenes dentarios humanos en estado de campana. Materiales y Métodos Se obtuvieron preparados histológicos de 4 maxilares fetales incluidos en parafina en el archivo de bloques de la cátedra de Histología de la Facultad de Odontología, UdelaR. Se procedió al corte de los mismos en secciones para técnica de rutina (HE) y de IHQ para MCM 4, 5 y 6. Resultados: Las diferentes regiones del órgano del esmalte mostraron 100 % de positividad en el estrato intermedio, una variación de 100 % a 0 % en el epitelio interno del órgano del esmalte, desde el sector cervical al sector incisal del mismo, y0% tanto en el retículo estrellado como en el epitelio externo del órgano del esmalte. Conclusiones: Los resultados obtenidos permitieron evidenciar y confirmar la acción proliferativa de las diferentes zonas del órgano del esmalte.

The aim of this study was to determine the expression of MCM4-5-6 in human tooth germs in the bell stage. Materials and methods: Histological samples were collected from four fetal maxillae placed in paraffin at the block archive of the Histology Department of the School of Dentistry, UdelaR. Sections were made for HE routine technique and for immunohistochemistry technique for MCM4-5-6. Results: Different regions of the enamel organ showed 100% positivity in the intermediate layer, a variation from 100% to 0% in the inner epithelium from the cervical loop to the incisal area, and 0% in the stellar reticulum as well as the outer epithelium. Conclusions: The results show and confirm the proliferative action of the different areas of the enamel organ.

JOSE VEROCAY - "Pragues pathologist". The history of a Latin-American doctor.

José Verocay (Paysandú 1876 - Eichwald/Dubí, Bohemia 1927) was a Uruguayan anatomopathologist, recognized worldwide as "Prague's pathologist" (Fig. 1). In 1910, he described, for the first time, the morphological structure later called Verocay's bodies, which are used for diagnosing schwannoma. He spent the end of the XIXth century and the beginning of XXth century in Charles-Ferdinand University in Prague. During the last years of his life, he tried unsuccessfully to reintegrate himself into the Uruguayan academic community. In 1927, he passed away in Eichwald, Teplitz district, Bohemia. Keywords: Prague's pathologist - Veroca y - Verocay's bodies.

José Verocay, el "patólogo de Praga" (1876-1927) / José Verocay, "Prague's pathologist" (1876-1927) / José Verocay, "o patologista de Praga" (1876-1927)

José Verocay (Paysandú, 1876-Teplitz Bohemia, 1927) fue un médico anatomopatólogo uruguayo de reconocimiento internacional, quién en 1910 describió, por primera vez, las estructuras que más tarde fueran nombradas como "cuerpos de Verocay", consideradas de fundamental importancia en el diagnóstico de Schwannoma (a pesar de no ser exclusivos del mismo). Su formación personal y científica se desarrolló en Europa en la Universidad Carolina de Praga, culminando con el máximo cargo académico posible de obtener en sus condiciones, el Privat Dozent (1910). Luego de su exilio, en 1919 regresa a Uruguay donde obtiene el cargo de Profesor de Anatomía Patológica en la Escuela de Odontología (1925). Ese mismo año aspira al cargo de Profesor de Anatomía Patológica de la Facultad de Medicina, cargo al cuál no accede generando una gran controversia entre médicos y estudiantes. En 1927 debido al deterioro de su salud, decide viajar a Viena en pos de su cura, en Uruguay se le realiza un Homenaje público a iniciativa de los estudiantes de odontología de la época, realizado en el Salón de Actos de la Facultad de Medicina, en donde por aquellos años se formaban los futuros odontólogos. Allí los propios estudiantes lo proclaman: "Maestro insigne de la generación médica actual", "Profesor por derecho propio de la Juventud médica". Fallece en Eichwald, distrito de Teplitz, Bohemia, en 1927, con 51 años de edad. Este artículo busca ser un breve repaso de su trayectoria académica en el Uruguay y en el mundo.

José Verocay (Paysandú 1876-Teplitz Bohemia 1927) was an Uruguayan pathologist of international recognition. In 1910 he described for the first time the structures that were later named "Verocay's bodies", considered of fundamental importance in the diagnosis of schwannoma (also present in other pathologies). His personal and scientific training was carried out in Europe at the University Carolina in Prague, culminating with the maximum academic position, Privat Dozent (1910). After his exile, in 1919, he returned to Uruguay where he obtained the position of Professor of Pathological Anatomy at the School of Dentistry (1925). That year he aspired to the position of Professor of Pathological Anatomy of the Faculty of Medicine, a position which he did not get, generating a great controversy between doctors and students. In 1927 due to the deterioration of his health, he decided to travel to Vienna looking after his cure. In Uruguay a public tribute was made by the initiative of the students of dentistry, it took place in the Hall of Acts of the Faculty of Medicine, where, in those years, the future odontologists were educated. There, the students themselves proclaimed him "Master of the current medical generation", "Professor in his own right Medical Youth". He passed away in Eichwald, Teplitz district in Bohemia, in 1927 at the age of 51. This article seeks to be a brief review of his academic career in Uruguay and in the world.

José Verocay (Paysandú, 1876-Teplitz Bohemia, 1927) foi um anatomopatologista médico uruguaio de reconhecimento internacional, que em 1910 descreveu, pela primeira vez, as estruturas que mais tarde foram chamadas "corpos de Verocay", considerados de fundamental importância na diagnóstico de schwannoma (apesar de não ser exclusivo dele). Seu treinamento pessoal e científico foi desenvolvido na Europa na Universidade da Carolina em Praga, culminando com o máximo de posição acadêmica possível para obter nas suas condições, o Privat Dozent (1910). Após o seu exílio, em 1919 voltou ao Uruguai onde obteve o cargo de Professor de Anatomia Patológica na Faculdade de Odontologia (1925). No mesmo ano, ele aspirou ao cargo de Professor de Anatomia Patológica da Faculdade de Medicina, cargo que não tem acesso a gerar uma grande controvérsia entre médicos e estudantes. Em 1927, devido à deterioração de sua saúde, ele decidiu viajar para Viena em busca de sua cura, no Uruguai foi feito um tributo público a iniciativa dos estudantes de odontologia da época, realizada no Salão da Assembléia da Faculdade de Medicina, onde naqueles anos os dentistas futuros foram formados. Os próprios estudantes proclamam: "Mestre da geração médica de hoje", "Professora por direito próprio da juventude médica". Ele morreu em Eichwald, distrito de Teplitz, Bohemia, em 1927, com 51 anos de idade. Este artigo pretende ser uma breve revisão de sua carreira acadêmica no Uruguai e no mundo.

Comparative Study of the Minichromosome Maintenance Proteins Complex (MCM 4/5/6) in Ameloblastoma and Unicystic Ameloblastoma.

INTRODUCTION: Solid/conventional ameloblastoma (AM) and unicystic ameloblastoma (UAM) are the most frequent benign epithelial odontogenic tumors located in the maxillary region, and their treatment usually consists of extensive surgical resection. Therefore, it is relevant to study molecular markers to better understand the biological behavior of these tumors. The aim of this study was to describe and compare the expression of proteins related to cellular proliferation: Ki-67 and MCM4-6 complex. MATERIALS AND METHODS: An immunohistochemistry technique was performed, with antibodies against Ki-67, MCM4, MCM5, and MCM6, in 10 AM and 10 UAM tumors. The results were quantified using label index and analyzed statistically. RESULTS: AM and UAM had greater expression of MCM6, followed by MCM5, MCM4, and Ki-67 ( P < .05). Immunoexpression of Ki-67 and MCM5 was exclusively nuclear, whereas the expression of MCM4 and MCM6 was nuclear and cytoplasmic. CONCLUSION: The results suggest that MCM5 is a trustable cell proliferation marker with higher sensitivity compared with Ki-67 and may be useful to predict the biological behavior of AM and UAM. Despite this, further studies are necessary, including a correlation with clinical parameters to confirm these findings.