Association of increased osteopontin and splice variant-c mRNA expression with HER2 and triple-negative/basal-like breast carcinomas subtypes and recurrence.

Osteopontin, a secreted phosphoglycoprotein, promotes tumor progression through binding to integrins and CD44 cell receptors. Its overexpression has been correlated with metastasis and adverse outcome in several neoplasms. In breast carcinoma, osteopontin mRNA and its splicing variant-c, a suggested marker for transformed cells, have not been extensively analyzed. Immunohistochemistry was performed in 415 breast carcinomas to examine total osteopontin and osteopontin-c protein distribution. RNA was extracted and retrotranscribed to cDNA from 309 tumors classified into immunophenotypes and in six cell lines representing the breast cancer subtypes. Total osteopontin and osteopontin-c mRNA levels were measured by quantitative RT-polymerase chain reaction. The median fold change of total osteopontin mRNA was higher in HER2-positive (fold-change = 14.7) and triple-negative/basal-like (fold-change = 14.7) tumors, whereas osteopontin-c mRNA was elevated in triple-negative/basal-like subtype (fold-change = 2.8). Total osteopontin levels were increased in SK-BR-3 (HER2-positive) and MDA-MB-468 (triple-negative/basal-like) cell lines. Higher total and osteopontin-c mRNA levels were seen in tumors of high grade, with necrosis, positive nodal status and high Nothingam Prognostic Index score. Disease-free survival was significantly shorter for patients whose tumors overexpressed total osteopontin (67% vs 73%). Moreover, increased osteopontin-c stratified subgroups of patients at higher risk of recurrence among immunophenotypes, especially in triple-negative/basal-like subtype (70% vs 83%). By multivariate analyses for disease-free survival, osteopontin-c emerged as a significant predictor of relapse. In summary, our data showed an association of osteopontin with poor prognostic factors, aggressive subtypes HER2 and triple-negative/basal-like, and higher risk of recurrence.

Imaging cytometry for counting circulating tumor cells: comparative analysis of the CellSearch vs ImageStream systems.

Circulating tumor cell (CTC) enumeration is important clinically for identifying prognostic and predictive factors in patients with solid cancers. The CellSearch device (Veridex) is an immunomagnetic CTC selection and enumeration system used in clinical practice. The ImageStream (Amnis) combines the strengths of flow cytometry and fluorescent microscopy in a single platform and has potential application for CTC counting. The performance in CTC enumeration was compared between the ImageStream and CellSearch systems. Various numbers of PANC-1 tumor cells were spiked into 7.5 mL of peripheral blood from a healthy donor. Before cell analysis by the ImageStream, tumor cell enrichment was performed by immunomagnetic selection with anti-EpPCAM. Anti-CD45 and anti-CK markers were used to discriminate between tumor cells and leukocytes. The ratios of tumor cells recovered from each dilution were calculated for both methods. The Wilcoxon rank test was applied to compare the results of the two methods and the reference value. The results of the two tested methods differed significantly from the reference value, but did not differ between them. Nevertheless, lower level of trueness and precision was observed in ImageStream when fewer numbers of CTCs were analyzed. Our results suggest that ImageStream platform for CTC enumeration has a potential value for the early diagnosis of disseminated disease, but needs an improvement of precision for the enumeration of low number of CTC.

[Mediterranean and Western dietary patterns in adult population of a Mediterranean area; a cluster analysis]. / Patrón de dieta mediterránea y occidental en población adulta de un área mediterránea; un análisis cluster.

OBJECTIVE: To identify dietary patterns among participants in a representative nutritional survey in the Valencia Community, and to analyze the association with socio-demographic characteristics and lifestyles. METHODS: Data for this study were from 1803 participants (973 women) in the Nutrition and Health Survey conducted in 1994 on a representative sample of adult population of Valencia Community. Diet was assessed by a validated food frequency questionnaire. Foods intakes were adjusted for 1,000 calories and grouped in 26 groups. Cluster analysis was used to identify dietary patterns using standardized values of the variables (z-scores). RESULTS: Three dietary patterns were identified and labeled as follows: the Prudent pattern (57.2%), characterized by a low-medium intake of most food of groups; the Mediterranean pattern (29.1%) characterized by high intake of fruits, vegetables, fish, poultry, cheese, and legumes; and the Western pattern (13.7%) characterized by high intake of meat and processed meats, high fat content foods, sweets and sugar, beverages, and alcoholic beverages. The Mediterranean pattern obtained higher scores for known diet quality index defined a priori. Using the Mediterranean pattern as reference, Western pattern included significantly more young people, higher number of men and smokers, and the Prudent pattern higher number of men, lower physical activity and lower alcohol consumption. CONCLUSION: Three dietary patterns were identified among participants in the Nutrition Survey of Valencia conducted in the mid-1990S: Prudent, Mediterranean and Western. The Prudent pattern was the most prevalent; the Mediterranean pattern was associated with healthier lifestyles and behaviors; and the Western pattern, the less prevalent although more frequently followed by youth, men and smokers. Further Nutrition Surveys should be carried out to make nutritional surveillance and analyze health effects of these observed patterns.

Antecedentes/objetivo: El objetivo de este estudio ha sido identificar patrones dietéticos a partir de los datos recogidos en la Encuesta de Nutrición y Salud de la Comunidad Valenciana realizada sobre una muestra representativa de población adulta y explorar los posibles factores asociados a los patrones identificados. Metodología: Un total de 1.803 individuos adultos (973 mujeres) participaron en la encuesta de Nutrición y Salud realizada en 1994 en la Comunidad Valenciana. La dieta fue evaluada mediante cuestionario de frecuencia alimentaria (CFA) validado de 93 ítems alimentarios. Las ingestas de alimentos se ajustaron por mil calorías y se crearon 26 grupos de alimentos usando valores estandarizados (z-scores) para la identificación de patrones dietéticos por el método análisis de k-medias prefijando 3 clúster. Se usó regresión logística multinomial múltiple para explorar la asociación entre patrones y variables sociodemográficas, antropométricas y de estilos de vida. Resultados: Se identificaron tres patrones dietéticos denominados como Prudente, Mediterráneo y Occidental. El patrón Prudente (57,2%) se caracterizó por un consumo intermedio de los principales grupos de alimentos; el Mediterráneo (29,1%) destacó por un elevado consumo de frutas, verduras y pescado; y el Occidental (13,7%) por un alto consumo de carnes rojas, embutidos, platos preparados, croquetas, bebidas azucaradas, dulces, chocolates y bebidas alcohólicas. El patrón Mediterráneo presentó las mayores puntuaciones para varios índices de calidad alimentaria analizados y definidos a priori en la literatura. Usando como referencia el patrón Mediterráneo, los que seguían un patrón Occidental fueron significativamente más jóvenes, un mayor número de hombres y fumadores; los que seguían un patrón Prudente presentaron un mayor número de hombres, no practicaban actividad física regular y menor consumo de alcohol. Conclusión: De los tres patrones dietéticos identificados como Prudente, Mediterráneo y Occidental en adultos de la Comunidad Valenciana a mediados de los noventa, el patrón Prudente fue el más prevalente, el Mediterráneo el que se asoció a conductas y hábitos de vida más saludables, y el Occidental el menos frecuente aunque fue más seguido entre jóvenes, hombres y fumadores. Se deberían realizar encuestas nutricionales que permitan hacer vigilancia nutricional y analizar la evolución de estos patrones dietéticos y sus posibles efectos sobre la mortalidad en población española.