Abstract
Background . During the last years several trials emerged demonstrating high tumour heterogeneity, including those on colorectal cancer. Objective. These findings made us initiate a meta-analysis of trials dedicated to this question. Materials and methods. We searched PubMed database, ASCO and ESMO abstracts for publications presented until August 2016. Studies which compared concordance of KRAS, NRAS, BRAF and PIK3CA mutations between primary tumour and metastases of colorectal cancer and which included more than 10 patients were included in meta-analysis. Meta-analysis was performed using Review Manager (RevMan), version 5.3. Results. Statistically significant differences were observed in KRAS (5 %; RR 0.95; 95 % CI 0.92–0.98; р = 0.003), PIK3CA (7 %; RR 0.93; 95 % CI 0.86–0.99; р = 0.04) mutational status, but not BRAF and NRAS. We observed no significant publication-associated systematic errors. KRAS discordance was significantly higher between primary tumour and lymph node metastases – 13.2 % (р = 0.036). Conclusions. A possibility of KRAS discordance between primary tumour and colorectal cancer metastases was demonstrated. Considering a small number of patients with discordance it is necessary to distinguish a high-risk discordance group, which will require an additional mutational analysis of metastatic nodes tissue.
Highlights
During the last years several trials emerged demonstrating high tumour heterogeneity, including those on colorectal cancer
These findings made us initiate a meta-analysis of trials dedicated to this question
Studies which compared concordance of KRAS, NRAS, BRAF and PIK3CA mutations between primary tumour and metastases of colorectal cancer and which included more than 10 patients were included in meta-analysis
Summary
Метаанализ исследований, посвященных изучению конкордантности мутационного статуса генов между первичной опухолью и метастазами рака толстой кишки. Цель исследования – проведение метаанализа работ, посвященных изучению данного вопроса при раке толстой кишки. Основными критериями включения результатов исследования стали: сравнение мутационного статуса генов KRAS, NRAS, BRAF, PIK3CA в первичной опухоли и метастазах с числом больных, доступных для анализа, 10 и более. Статистически значимо выявляются случаи расхождения мутационного статуса генов KRAS (5 %; отношение рисков 0,95; 95 % доверительный интервал 0,92–0,98; р = 0,003), PIK3CA (7 %; отношение рисков 0,93; 95 % доверительный интервал 0,86–0,99; р = 0,04), но не BRAF и NRAS, между первичной опухолью и метастазами. Доказана возможность дискордантности мутационного статуса гена KRAS между первичной опухолью и метастазами. Ключевые слова: рак толстой кишки, конкордантность, мутация генов, KRAS, NRAS, BRAF, PIK3CA, метаанализ. Blokhin Russian Cancer Research Center, Ministry of Health of Russia; Kashirskoe Shosse, Moscow 115478, Russia
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