Cell cycle aberration in ameloblastoma and adenomatoid odontogenic tumor: As evidenced by the expression of p53 and survivin.

Context: p53 and survivin are involved in cell cycle progression and inhibition of apoptosis, respectively. Survivin is a unique protein which functions in progression of cell division and inhibits apoptosis leading to cell proliferation and cell survival. According to the literature, mutation of p53 leads to promotion of survivin function. Thus, the importance of cell cycle aberration and uncontrolled proliferation resulting from mutation of p53 and up‑regulation of survivin is discussed. Aims: To assess the role of p53 and survivin in ameloblastoma and adenomatoid odontogenic tumor (AOT). Settings and Design: The percentages of positive tumor cells were considered for statistical evaluation. Nuclear labeling index for p53 and nuclear, cytoplasmic and combined labeling index for survivin was obtained from the stained slides. Materials and Methods: Immunohistochemical expression of p53 and survivin was done qualitatively and quantitatively in 25 cases each of ameloblastoma and AOT. Statistical Analysis Used: Mann–Whitney U‑test, Wilcoxon signed ranks test and Pearson’s correlation test. Results: Quantitatively, p53 and survivin expression was statistically significant in AOT (P = 0.003) and qualitatively, in ameloblastoma (P = 0.004). Survivin expression was significant (P = 0.002) between the study groups unlike that of p53 (P = 0.554). Conclusions: There was no much difference in p53 expression in ameloblastoma and AOT suggestive of cell cycle aberration in both the odontogenic tumors, but significant difference in survivin expression in ameloblastoma and AOT with higher percentage of positive cells in ameloblastoma may be indicative of an aggressive behavior of ameloblastoma.

Expresión de KI67, P53, BCL2 en el carcinoma de mama en nuestro medio / Ki67 expression, P53, Bcl-2 in breast carcinoma in our midst

Objetivo: Determinar la expresión del Ki67, p53 y Bcl2 en pacientes con diagnóstico de cáncer de mama en nuestro medio. Métodos: Se realizó un estudio descriptivo, retrospectivo de diseño no experimental de tipo transeccional de la expresión por técnica inmunohistoquímica de los marcadores moleculares Ki67, p53 y Bcl2 de casos con el diagnóstico de carcinoma de mama en un grupo de 110 mujeres que acudieron consecutivamente a una consulta de mama en la Clínica Docente los Jarales (CDLJ) durante el período comprendido 2005 - 2011. La muestra fue intencional y conformada por los casos seleccionados del archivo historias de la consulta que cumplieron los siguientes criterios de inclusión. Resultados: La edad promedio fue de 51,81 años, más del 60 % eran posmenopáusicas. El tumor en la mayoría se localizó en la mama izquierda, Más del 60 % de los tumores tenían un tamaño entre los 2 a 5 cm y más del 80 % metástasis regionales. En más de la mitad de los tumores se observó inmunoexpresión de los receptores hormonales. El 60 % de los tumores correspondieron al subtipo luminal A. El Ki67 se observó en mayor porcentaje de casos en los tumores de pacientes entre 25 a 46 años y el p53 y Bcl2 en aquellos entre 36 a 46 y 58 a 68 años respectivamente. El Ki67, p53 y Bcl2 marcaron en mayor número de casos clasificados estadio clínico II-III, como de tumores entre 2 a 5 cm y con más de 7 ganglios metastásicos. Conclusión: Es necesario generar aún más evidencia sobre las características propias de nuestra población femenina afectada por la neoplasia para comprender su comportamiento en ellas y racionalizar en consecuencia lo correspondiente a su terapéutica.

Objective: To determine the expression of Ki67, p53 and Bcl2 in patients diagnosed with breast cancer in our midst. Methods: A descriptive, retrospective design nonexperimental transeccional expression by immunohistochemistry of molecular markers Ki67, p53 and Bcl2 in cases with a diagnosis of breast cancer in a group of 110 consecutive women attending a breast query the Jarales Teaching Clinic (CDLJ) during the period from 2005 to 2011. The sample was composed of intentional and file cases selected records of the query that met the following inclusion criteria. Results: The mean age was 51.81 years, over 60 % were postmenopausal. The tumor was located in most of the left breast, over 60 % of the tumors had a size between 2-5 cm and over 80 % regional metastases. In more than half of the tumors was observed immunoexpression hormone receptors. 60 % of the tumors corresponded to the luminal subtype A. Ki67 was observed in the highest percentage of cases in tumors from patients aged 25 to 46 years and the p53 and Bcl2 in those between 36 to 46 and 58 to 68 respectively. The Ki67, p53 and Bcl2 marked in more cases classified clinical stage II-III, as tumors between 2-5 cm and more than 7 metastatic nodes. Conclusion: It is necessary to generate further evidence on the characteristics of our female population affected by neoplasia to understand their behavior accordingly rationalize them and what matches your therapy.

Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

Tumor del estroma gastrointestinal (TEGI): un estudio de su frecuencia y perfil de inmunohistoquímica / Gastrointestinal stromal tumors: analysis of 51 cases, immunohistochemical expression

Background: Gastrointestinal Stromal Tumors (GIST) have a mesenchymal origin and correspond to 1 percent of all gastrointestinal tumors. They have a benign behavior in approximately 75 percent of cases. They express CD117, CD34, smooth muscle actin, S-100 and desmin, markers that are useful in the differential diagnosis of smooth muscle tumors and those of neurogenic origin. Aim: To report our experience with GIST. Material and Methods: A retrospective, observational study. The pathology reports of GIST in the period 2004-2008 were reviewed. Immunohistochemical expression, pathological grade, mitotic index and histological patterns were reviewed. The medical records of patients were reviewed to obtain age and gender, location, size and presence of metastases. Results: A total of 51 GIST were identified, coming from 21 males and 30 females. Nineteen tumors were located in the small bowel, 18 in the stomach, four in the rectum, two in the colon and in five, the location was not specified. In 28 cases, the pathological pattern was spindle cell, in 12 mixed, in six epithelioid, in three pleomorphic, in one signet ring cell and giant cell in one. Forty nine percent of tumors were of high grade. Metastases were found in the liver in two cases, in the omentum in two and in the spleen, kidney, retroperitoneum and pancreas, in one case each. Two had lymph node involvement. Conclusions: GIST tumor corresponded to a 0.12 percent of all pathology reports during the study period. Most tumors in this series were of high grade.

Introducción: Los Tumores del Estroma Gastrointestinal (TEGI) son de origen mesenquimal comprendiendo el 1 por ciento de todos los tumores GI. Son benignos del 70 a 80 por ciento. Expresan CD117, CD34, actina de músculo liso, S-100 y desmina, marcadores útiles en el diagnóstico diferencial de tumores de músculo liso y tumores de origen neurogénico. Material y Método: Es un estudio retrospectivo y descriptivo. Se revisaron los reportes en el período 2004-2008 registrados como TEGI, valorando la expresión Inmunohistoquímica, grado histológico, índice mitótico, y patrones histológicos. Del reporte histológico se obtuvo la edad y sexo del paciente, localización, tamaño y metástasis. Resultados: Se recolectaron 51 casos corroborados como TEGI. Encontrando una prevalencia del sexo femenino (30) y una edad media de 52 años. Las localizaciones fueron: Intestino delgado (19), estómago (18), no especificado (5), recto (4), colon (2), retroperitoneo (2), no encontramos en esófago. Los patrones encontrados fueron el fusocelular (28), mixto (12), epitelioide (6), pleomórfico (3), células en anillo de sello (1), células gigantes (1). La mayoría (49 por ciento) fue de alto grado, presentando metástasis a hígado (2), ganglios (2), epiplón (2), bazo (1), riñón (1), retroperitoneo (1) y páncreas (1). Discusión: Se realizaron un total de 41.035 estudios histopatológicos, de los cuales 51 casos corresponden a LEGI, esto equivale al 0,12 por ciento. Encontramos tumores en los que su morfología, tamaño e índice mitótico fueron de bajo grado y presentaron metástasis y recidivas al momento del diagnóstico. Veinticinco casos fueron de alto grado (49 por ciento), lo cual es mayor a lo reportado por la literatura 20-30 por ciento, probablemente porque este es un hospital de concentración y generalmente los pacientes acuden a atención médica en una etapa avanzada de la enfermedad.

Expresión de marcadores de proliferación celular e invasión tisular en cáncer papilar del tiroides y su asociación con metástasis ganglionares / Expression of proliferation and invasion markers in papilary thyroid carcinoma with and without lymph node involvement

Background: Several molecules that may have a role in tumor proliferation, differentiation and invasion, have been detected in thyroid carcinoma. Some of these molecules are NIS, c-MET, TIMP1 an ephrinB2. Aim: To detect the presence of these molecules in tissue samples of thyroid carcinoma and relate their expression to the biological behavior of the tumor. Material and Methods: Tissue samples were prospectively obtained from 35 patients operated for a papillary thyroid carcinoma. Twelve patients had regional lymph node involvement. NIS, c-MET, TIMP1 and EphrinB2 were detected by real time polymerase chain reaction(RT-PCR) and immunohistochemistry. Results: The expression of markers by RT-PCR was non significantly higher among tumors with lymph node involvement. Immunohistochemistryshowed a significantly lower nuclear expression and a higher cytoplasmatic expression of EphrinB2 in tumors with lymph node involvement. Conclusions: Immunohistochemical expression of EphrinB2 could be useful for the initial staging of papillary thyroid carcinoma.

Expresion inmunohistoquimica e inestabilidad microsatelital en el sindrome de lynch / Immunohistochemical expression and microsatellite instability in Lynch syndrome

Las mutaciones de los genes MLH1 y MSH2 son frecuentemente implicadas en el síndrome de Lynch. La expresión inmunohistoquímica (IHQ) es una forma simple de selección para pruebas moleculares. Se analizó la IHQ de MLH1 y MSH2 en pacientes con síndrome de Lynch (16 casos) y pacientes menores de 50 años sin antecedentes familiares (25 casos). Se estudiaron 41 tumores de un grupo de pacientes (64% mujeres) de edad promedio 40.7 años (rango: 16-75). Se obtuvieron resultados concluyentes en 40 casos (97.6%). Dieciocho casos (45%) presentaron falta de expresión (MLH1 negativa: 11 casos; MSH2 negativa: 6 casos; MLH1 negativa y MSH2 negativa: 1 caso), con una incidencia significativamente mayor en pacientes con síndrome de Lynch (68.7% vs. 28%, p=0.01). Entre los casos esporádicos, 5 casos (20%) mostraron falta de expresión MLH1 y 2 casos (8%) con falta de expresión MSH2. La falta de expresión IHQ presentó una fuerte asociación con inestabilidad microsatelital alta (IMS): expresión normal: 5.9%, expresión negativa: 92.3%, P<0.0001. Los índices de sensibilidad y especificidad de la IHQ para detectar IMS fueron de 92.3% y 94.1% respectivamente. Los patrones de IHQ y de IMS no se relacionaron a ninguna característica histopatológica. En conclusión, el análisis inmunohistoquímico de las proteínas MLH1 y MSH2 fue altamente sensible y específico para detectar IMS y permitió identificar en un 45% de los casos la proteína alterada. El índice de falta de expresión IHQ entre los casos esporádicos diagnosticados antes de los 50 años justifica su implementación sistemática en este grupo de pacientes.

Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p<0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (< 50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.