RESUMEN
BACKGROUND: Human polo-like kinase 1 (PLK1) expression has been associated with inferior outcomes in colorectal cancer. Our aims were to analyse PLK1 in rectal cancer, and its association with clinicopathological variables, overall survival as well as tumour regression to neoadjuvant treatment. METHODS: PLK1 expression was quantified with immunohistochemistry in the centre and periphery (invasive front) of rectal cancers, as well as in the involved regional lymph nodes from 286 patients. Scores were based on staining intensity and percentage of positive cells, multiplied to give weighted scores from 1-12, dichotomised into low (0-5) or high (6-12). RESULTS: PLK1 scores in the tumour periphery were significantly different to adjacent normal mucosa. Survival analysis revealed that low PLK1 score in the tumour periphery had a hazard ratio of death of 0.59 in multivariate analysis. Other predictors of survival included age, tumour depth, metastatic status, vascular and perineural invasion and adjuvant chemotherapy. There was no statistically significant correlation between PLK1 score and histological tumour regression in the neoadjuvant cohort. CONCLUSION: Low PLK1 score was an independent predictor of superior overall survival, adjusting for multiple clinicopathological variables including treatment.
Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Evaluación de Resultado en la Atención de Salud/métodos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Neoplasias del Recto/metabolismo , Regulación hacia Arriba , Anciano , Quimioradioterapia/métodos , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Análisis Multivariante , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Análisis de Supervivencia , Quinasa Tipo Polo 1RESUMEN
Circulating tumour cells (CTCs) hold great potential as liquid biopsies to prognosticate disease and guide treatment in colorectal cancer. However, their emerging role in determining the molecular phenotype of tumour metastasis carries even more promising clinical use in the provision of comprehensive biomarker detection for targeted therapies and determination of drug resistance. The isolation of CTCs is technology dependent, and in the case of epithelial cell adhesion molecule-based platforms, the ability to detect cells that have undergone the epithelial to mesenchymal transition (EMT) is ineffective. CTCs displaying a mesenchymal phenotype are believed to have an increased metastatic potential. The rarity of CTCs provides another challenge in the enumeration of these cells. The future will likely involve the analysis of individual CTCs at any stage of the EMT in order to provide real-time phenotypic and molecular snapshots capable of tracking the dynamic evolution of tumour progression over time.