Abstract
Aim. To study pathological and molecular features of liver metastases of colon adenocarcinoma. Material and methods . DNA mismatch repair (MMR), CXCR4 expression, Ki-67 proliferative activity were investigated in 125 cases of colon adenocarcinoma with liver metastases. First group consisted of 94 cases of tumor with liver metastases at diagnosis. The second group consisted of 31 cases with stage II disease at diagnosis, but subsequently these patient metastases. In second group KRAS mutation was investigated. The control group included 22 cases of stage II colon adenocarcinoma without disease progression. MMR was studied in 325 cases of colon adenocarcinoma without known stage. Results . MMR deficiency (dMMR) didn’t revealed in group 1 and 2. The frequency of deficiency MMR in the general population of colon adenocarcinoma was 8%. Low level of expression of CXCR4 in group I and II was revealed in 16% of cases, in control group – in 73%. Low level of Ki-67 was revealed in 5% of cases of liver metastases (group 1 and 2), the frequency of KRAS mutations was 45%. Conclusion. Colon adenocarcinoma with liver metastases is characterized by aggressive immunophenotype: high expression rates CXCR4, Ki-67, and preferentially retained MMR function.
Highlights
Low level of expression of CXCR4 in group I and II was revealed in 16% of cases, in control group – in 73%
Increased expression of Ki-67 is a poor prognostic marker for colorectal cancer patients: a metaanalysis
Summary
Всего было изучено 125 наблюдений аденокарциномы толстой кишки с метастазами в печень. В 1-й группе было 94 наблюдения опухоли с метастазами в печень на момент постановки диагноза, во 2-й – 31 наблюдение опухоли II стадии на момент постановки диагноза, однако в дальнейшем у этих пациентов развились метастазы. Группа контроля составлена из 22 пациентов со II стадией аденокарциномы толстой кишки, прослеженный безрецидивный период у которых составил 5 лет. Было проведено иммуногистохимическое исследование экспрессии генов репарации неспаренных нуклеотидов ДНК (MSH2, MSH6, PMS2, MLH1), экспрессии рецептора к хемокину CXCR4, оценка индекса пролиферативной активности Ki-67. В 325 наблюдениях аденокарциномы толстой кишки без учета стадий также было проведено иммуногистохимическое исследование генов MMR (3-я группа). Экспрессия MLH1, гена репарации неспаренных нуклеотидов ДНК (MMR): a – выпадение экспрессии MLH1 в клетках аденокарциномы локализованной формы, сохранная реакция в клетках стромы (коричневое окрашивание); б – сохранная экспрессия MLH1 в метастазе аденокарциномы толстой кишки в печень. Экспрессия CXCR4, рецепторы к хемокину в аденокарциноме толстой кишки: a – низкий уровень экспрессии, коричневая гранулярная реакция в цитоплазме опухолевых клеток; б – высокий уровень экспрессии. ×400
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