ОПРЕДЕЛЕНИЕ ЭКСПРЕССИИ TLE3 ПРИ СЕРОЗНОМ РАКЕ ЯИЧНИКОВ

Indications for treatment of ovarian cancer with taxane derivatives requires individualization, and this is necessary to have a reliable marker allowing to determine the rationality of the using of cytostatics. One of the progressive trends in this issue may be related to the immunohistochemical identification in removed tumors of transducing-like protein TLE3, which is a transcriptional repressor that is involved in the differentiation of epithelial cells and carcinogenesis. In the present study retrospectively analyzed 100 patients and prospectively 73 patients with serous ovarian cancer treated in MCCOC from 2007 to2014. In the first stage of treatment all patients underwent debulking surgery followed by adjuvant chemotherapy with platinum and taxanes or cyclophosphamide. Providing of immunohistochemical investigation of removed tumor tissue was carried out with a standard peroxidase-antiperoxidase method. Statistically significant influence of expression of TLE3 on disease-free survival (log-rank = 0.023). Five-year disease-free survival in the group with positive expression of TLE3 was 1.2 times higher than in the group with negative expression of TLE3 (0.490; 95% confidence interval [0.287, 0.837] and 0.261; 95% confidence interval [0.179, 0.380], respectively). An objective response in patients with TLE3-positive tumors was obtained in 93.8%. There were no benefits of taxanes using compared with cyclophosphamide in group of patients with negative expression TLE3. Thus, it is advisable to evaluate the expression of TLE3 to identify groups of patients that are sensitive to chemotherapy with taxanes.Показания к лечению рака яичников производными  таксанов требуют индивидуализации,  а для этого необходимо располагать надежным маркером, позволяющим достоверно определять целесообразность назначения цитостатиков. Одно из прогрессивных направлений в этом вопросе может быть связано с иммуногистохимической идентификацией в удаленных  опухолях трансдуцин  подобного  протеина  TLE3, который представляет собой транскрипционный репрессор,  принимающий участие в дифференцировке  эпителиальных клеток и канцерогенезе. В настоящем исследовании ретроспективно проанализированы 100 пациенток и проспективно 73 пациентки с серозным раком яичников, пролеченных в МГКОД с 2007 г. по 2014 г.г. На первом этапе всем пациенткам выполнялась циторедуктивная операция, после чего назначалась адъювантная полихимиотерапия с использованием препаратов платины и таксанов или циклофосфамида.  Проведение иммуногистохимического исследования  удаленной опухолевой ткани осуществлялось по стандартной пероксидазно-антипероксидазной  методике. Выявлено статистически значимое влияние на ВСР экспрессии TLE3 (pлог-ранг = 0,023). Пятилетняя ВСР в группе с положительной экспрессией TLE3 в 1,2 раза выше, чем в группе с отрицательной экспрессией TLE3 (0,490 (95%ДИ [0,287; 0,837]) и 0,261 (95%ДИ [0,179; 0,380]) соответственно).  Объективный ответ у пациенток с ТЛЕ-3 положительной опухолевой экспрессией  получен в 93,8%. Не выявлено преимуществ использования таксанов по сравнению с циклофосфаном в группе с отрицательной экспрессией TLE3.Таким образом, целесообразно использовать оценку экспрессии TLE3 с целью выявления групп пациенток, чувствительных к химиотерапии  таксанами

The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl.

Papillary thyroid cancer (PTC) among individuals exposed to radioactive iodine in their childhood or adolescence is a major internationally recognized health consequence of the Chernobyl accident. To identify genetic determinants affecting individual susceptibility to radiation-related PTC, we conducted a genome-wide association study employing Belarusian patients with PTC aged 0-18 years at the time of accident and age-matched Belarusian control subjects. Two series of genome scans were performed using independent sample sets, and association with radiation-related PTC was evaluated. Meta-analysis by the Mantel-Haenszel method combining the two studies identified four SNPs at chromosome 9q22.33 showing significant associations with the disease (Mantel-Haenszel P: mhp = 1.7 x 10(-9) to 4.9 x 10(-9)). The association was further reinforced by a validation analysis using one of these SNP markers, rs965513, with a new set of samples (overall mhp = 4.8 x 10(-12), OR = 1.65, 95% CI: 1.43-1.91). Rs965513 is located 57-kb upstream to FOXE1, a thyroid-specific transcription factor with pivotal roles in thyroid morphogenesis and was recently reported as the strongest genetic risk marker of sporadic PTC in European populations. Of interest, no association was obtained between radiation-related PTC and rs944289 (mhp = 0.17) at 14p13.3 which showed the second strongest association with sporadic PTC in Europeans. These results show that the complex pathway underlying the pathogenesis may be partly shared by the two etiological forms of PTC, but their genetic components do not completely overlap each other, suggesting the presence of other unknown etiology-specific genetic determinants in radiation-related PTC

Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?

One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131Irelated risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiationrelated risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer

Comprehensive Clinical Assessment of 740 Cases of Surgically Treated Thyroid Cancer in Children of Belarus

OBJECTIVE: A retrospective study was designed to evaluate the results of surgical treatment and follow-up data in thyroid cancer patients less than 15 years old at the time of surgery. SUMMARY BACKGROUND DATA: Pediatric thyroid carcinomas have a high rate of lymph nodal and distant metastases. Risk factors for recurrences and postoperative morbidity have not been assessed yet in a representative series. METHODS: The group included 740 pediatric patients with thyroid cancer. Total thyroidectomy was performed in 426 (57.6%), lobectomy in 248 (33.5%), subtotal thyroidectomy in 58 (7.8%) cases, and 8 patients (1.1%) underwent partial lobectomy. RESULTS: The mean follow-up period was 115.8 months (range, 1.5–236.4 months). Recurrence was diagnosed in 204 cases (27.6%), including 73 local relapses (9.9%), 90 distant metastases (12.2%), and a combination of local and distant recurrences in 41 (5.5%) patients. Multivariate statistical assessment revealed the following independent parameters significantly associated with the risk of recurrent nodal disease: a young age at diagnosis, multifocal carcinomas, N1 status, and lack of neck lymph node dissection. For lung metastases, the significant risk factors were female gender, young age at diagnosis, and presence of symptoms. The observed 5- and 10-year survival for the entire group was 99.5% and 98.8%, respectively. Postoperative hypoparathyroidism was significantly associated with multifocal tumors, central compartment removal, and ipsilateral dissection. CONCLUSIONS: Total thyroidectomy followed by radioiodine therapy is an optimal treatment strategy that makes it possible to achieve a cure in a vast majority of pediatric patients with differentiated thyroid carcinomas. Risk of recurrence is strongly associated with tumor stage, extent of surgery, the young patient's age, and presence of symptoms at diagnosis