RESUMEN
PURPOSE: Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. RESULTS: Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. MATERIALS AND METHODS: Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. CONCLUSIONS: The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/metabolismo , Ganglios Linfáticos/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Barrera Hematoencefálica , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Riesgo , Análisis de Supervivencia , Transcriptoma , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
INTRODUCTION: Endoscopic para-aortic lymphadenectomy (PALN) is a crucial step in the management of gynecological cancers. However, some concerns exist on the completeness of PALN according to the route (transperitoneal vs. extraperitoneal single-port or multiport). We compared these three surgical techniques using a propensity score. METHODS: We retrospectively reviewed all patients undergoing an endoscopic PALN for a gynecological cancer from May 2010 to Mars 2015. Fifty-one patients had a single-port extraperitoneal PALN, 16 a multiport extraperitoneal PALN and 62 a transperitoneal PALN. Factors independently related to technique performances were tested on a multivariate model adjusted for a propensity score. RESULTS: The number of lymph nodes removed by transperitoneal route was 15 and extraperitoneal route single and multiport was 12. After adjustment for the propensity score of undergoing the extraperitoneal approach, no difference in the number of lymph node removed was noted (P=0.17). There was more lymphocyst after transperitoneal (17%) and multiport extraperitoneal PALN (19%) than after extraperitoneal PALN (2%) (P=0.04). Success rate of single-port extraperitoneal PALN was 94% (n=48). Four patients required a conversion to an open route due to vascular injury. DISCUSSION: Using a propensity score, single-port extraperitoneal route offers similar efficacy to perform PALN than transperitoneal or multiport extraperitoneal route but with less lymphocysts.
Asunto(s)
Neoplasias de los Genitales Femeninos/cirugía , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Puntaje de Propensión , Anciano , Análisis de Varianza , Conversión a Cirugía Abierta/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Neoplasias de los Genitales Femeninos/patología , Humanos , Laparoscopía/efectos adversos , Laparoscopía/instrumentación , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/instrumentación , Ganglios Linfáticos/patología , Linfocele/etiología , Persona de Mediana Edad , Peritoneo , Espacio Retroperitoneal , Estudios RetrospectivosRESUMEN
BACKGROUND: Endoscopic paraaortic lymphadenectomy (PALN), an important step in the management of gynecologic cancers, is associated with low morbidity. However, some concerns exist about the completeness of PALN according to the route (transperitoneal vs. single-port extraperitoneal). METHODS: This study retrospectively reviewed the records of patients who had undergone an endoscopic PALN for a gynecologic cancer from May 2010 to August 2014 at the authors' center. The findings showed that 44 patients had a single-port extraperitoneal PALN and 56 had a transperitoneal PALN. The factors independently related to technical performances were tested with a multivariate model adjusted for a propensity score. RESULTS: A median of 16 lymph nodes were removed by the transperitoneal route and 12 by the extraperitoneal route (p = 0.04). No difference in the number of lymph nodes removed was observed after adjustment for the propensity score of patients who underwent the extraperitoneal approach (p = 0.9). The transperitoneal route was associated with more lymphocysts (20 vs. 2% for the extraperitoneal approach) (p = 0.008). The success rate for the extraperitoneal PALN was 91% (n = 40), with the three remaining patients requiring conversion to the transperitoneal route due to a peritoneal breach. CONCLUSION: This propensity-score-adjusted study supports the conclusion that the efficacy of the single-port extraperitoneal route is similar to that of the transperitoneal route for PALN.