За последнее десятилетие интенсивного изучения опухолевого микроокружения получены многочисленные данные, свидетельствующие о критической роли стромы в канцерогенезе. Накопление генетических нарушений характерно не только для опухолевого эпителия, но и для ассоциированных с опухолью фибробластов. С применением технологии лазерной микродиссекции мы разделили эпителиальный и стромальный компоненты рака предстательной железы и провели микросателлитный анализ хромосомных районов 8р22, 13q14 и 16q23 в неопластических и стромальных клетках при раке предстательной железы и предраковых изменениях. В эпителии частота аллельных нарушений в локусах 8р22, 16q23 и 13q14 составила 48, 72 и 37% соответственно. В строме частота потери гетерозиготности и микросателлитной нестабильности в этих локусах была немного выше. В небольшом количестве молекулярные перестройки обнаружены как в эпителиальном (от 16 до 27%), так и в стромальном компоненте простатической интраэпителиальной неоплазии (от 7 до 22%). Выявлены статистически достоверные ассоциации потерь аллелей на хромосомах 16 и 13 в эпителии со степенью дифференцировки опухоли, стадией злокачественного процесса и метастазами в регионарных лимфоузлах. Результаты нашей работы свидетельствуют о том, что в строме рака предстательной железы происходят многочисленные мутационные события, частота которых не уступает частоте в опухолевом эпителии.

FREQUENT ALLELIC LOSSES IN TUMOR-ASSOCIATED STROMAL CELLS AND TUMOR EPITELIUM OF PROSTATE CANCER, by T. V. Kekeeva^{1, 2}, O. P. Popova² , P. V. Shegai³, L. E. Zavalishina³, Y. Y. Andreeva³, D. V. Zaletaev^{1, 2}, M. V. Nemtsova^{1, 2} (¹Medical Genetic Research Centre, Russian Academy of Medical Sciences, Moscow, 115478 Russia, ^*e-mail: zalnem@online.ru; ²Institute of Molecular Medicine, Sechenov Medical Academy, Moscow, 119992 Russia; ³Moscow Herzen Oncological Research Institute, Moscow, 125284 Russia). It has become increasingly clear that tumor microenvironment plays a critical role in carcinogenesis. Accumulation of genetic alterations is typical not only for cancer epithelial cells but tumor-associated fibroblasts as well. Tumor epithelia, tumor-associated stroma from prostatectomy specimens of patients with prostate cancer and cells from prostatic intraepithelial neoplasia (PIN) and adjacent stroma from males with PIN were isolated by using laser capture microdissection. Microsatellite allelotyping was evaluated using 4 highly polymorphic markers for chromosomal regions 8p22, 16q23–24 and 13q14. Incidences of alterations (loss of heterozygosity or allelic imbalance) were 48% for region 8p22, 72% for 16q23 and 37% for 13q14. The LOH frequencies in tumor-associated stroma cells were very similar. Alterations at chromosome 13q were significantly associated with advanced tumor stage, whereas AI at 16q was also associated with high Gleason score and lymph node metastasis. We find some incidences of allelic imbalance in premalignant lesions in epithelial (16–27%) and stromal (7–22%) components. Our results show that the frequencies of genetic aberrations are as high in stromal cells as in tumor cells.

Key words: prostate cancer, laser capture microdissection, loss of heterozygosity, allelic imbalance, tumor microenvironment.

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