RESUMEN
Normal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER+ breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast disease (n = 15)). Cyber-T identified differentially expressed genes. Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two-thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G-protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under-expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer-related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissue's response to an existing tumor.
Asunto(s)
Neoplasias de la Mama/química , Mama/química , Proteínas de Ciclo Celular/análisis , Epitelio/química , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción/análisis , Adulto , Biomarcadores de Tumor/análisis , Mama/anatomía & histología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Epitelio/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Mamoplastia , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
We conducted a study to examine the viability, host response, and volume retention characteristics of drilled human septal cartilage slurry when injected into an athymic nude mouse model. We injected 0.2 ml of the slurry into the hind limbs of 6 mice. The mice were sequentially sacrificed over a period of 180 days. Histologic reviews of the hind limbs were performed to determine the viability of injected chondrocytes, host response, and volume retention. Specimens were obtained and histomorphologic analysis was performed at 1, 30, 90, and 180 days after injection. We identified viable cartilage throughout the study. Cartilage injection was well tolerated, and minimal inflammatory reaction occurred without significant adverse effects. The injected bolus of cartilage was found to have progressively dispersed throughout the muscle over time. Our findings warrant further investigation with a larger cohort of nude mice or possibly human subjects.