RESUMO
This study was designed to identify predictive signatures of pathological complete response (pCR) in breast cancer treated by taxane-based regimen, using clinicopathological variables and transcriptomic data (Affymetrix Hgu133 Plus 2.0 devices). The REMAGUS 02 trial (n = 153,training set) and the publicly available M.D. Anderson data set (n = 133, validation set) were used. A re-sampling method was applied. All predictive models were defined using logistic regression and their classification performances were tested through Area Under the Curve (AUC) estimation. A stable set of 42 probesets (31 genes) differentiate pCR or no pCR samples. Single-or 2-probesets signatures, mainly related to ER pathway, were equally predictive of pCR with AUC greater then 0.80. Models including probesets associated with ESR1, MAPT, CA12 or PIGH presented good classification performances. When clinical variables were entered into the model, only CA12 and PIGH, remained informative (p = 0.05 and p = 0.005) showing that a combination of a few genes provided robust and reliable prediction of pCR.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Transcriptoma , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/química , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Anidrases Carbônicas/genética , Quimioterapia Adjuvante , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , RNA/análise , Receptores de Estrogênio/análise , Taxoides/administração & dosagem , Resultado do Tratamento , Proteínas tau/genéticaRESUMO
BACKGROUND: The METAVIR score, which is the most widely used score in France, was specifically elaborated and evaluated in chronic hepatitis C and has never been validated in HIV-hepatitis virus B (HBV) co-infected patients. AIMS: To validate the use of the METAVIR scoring system for activity and fibrosis on liver biopsies in co-infected HIV-HBV patients. METHODS: METAVIR scoring for activity and fibrosis was first conducted on both original and virtual slides by one pathologist for comparison. Then 55 biopsies turned into virtual slides were scored by three pathologists independently. RESULTS: The scoring comparison between virtual slides and glass slides showed an almost perfect agreement for fibrosis (weighted kappa (kappa(w)) 0.8) and a substantial agreement for activity (kappa(w) 0.68). The inter-observer agreement on virtual slides was moderate to almost perfect (kappa(w) 0.52 to 0.84) for fibrosis and was dependent on the pair of pathologists considered. The best agreement was obtained in scoring advanced fibrosis and cirrhosis versus significant fibrosis versus no or mild fibrosis (kappa(w) 0.70 to 0.84). The agreement for cirrhosis was rated moderate to substantial (kappa(w) 0.54 to 0.79). Agreement for activity was substantial (kappa(w) 0.66 to 0.8). CONCLUSIONS: This study validates the use of virtual slide technology to assess fibrosis and activity on liver biopsies. It also validates the use of the METAVIR score in co-infected HIV-HBV patients and illustrates the challenges in establishing the histological diagnosis of cirrhosis in the HIV-HBV context.