Histopathological characteristics and post-operative follow-up of patients with potentially radiogenic papillary thyroid carcinoma depending on oncocytic changes availability in the tumor cells.

AIM: To compare the frequency of main histopathological characteristics, 131І thyroid radiation doses, invasive properties and post-operative follow-up of patients of different age groups with potentially radiogenic papillary thyroid carcinoma (PTC) with the presence and absence of oncocytic changes in tumor cells. MATERIALS AND METHODS: PTC removed in 483 patients from high risk age-group for radiogenic thyroid cancer development (children and adolescents at the time of Chornobyl accident who lived in the northern regions of Ukraine: Kyiv, Zhytomyr, and Chernihiv regions) have been studied microscopically. RESULTS: The frequency of PTC with the presence of oncocytic changes (OCh) in tumor cells increased significantly with increasing of patients' age at the time of surgery: from 8.3% in children 4-14 years old to 54.3% in adults 39-48 years old (ptrend < 0.0001). The presence of such changes is associated with papillary and solid-trabecular dominant tumor growth pattern in more than 90% of cases in each age group. The mean 131І thyroid dose in the whole series of PTC patients with OCh was significantly lower compared to the same index in PTC patients without OCh (493.7 mGy and 765.8 mGy, respectively, p < 0.0001). In addition, regional metastases recurrences were revealed more frequently in patients with OCh in primary PTC compared with patients without OCh in primary tumor (7.2% vs 1.5%, p = 0.0022). CONCLUSIONS: Significantly increasing age-trend of OCh in PTC of patients affected by the Chornobyl fallout and operated at age from 4 to 48 years, as well as opposite decreasing linear age-trend of 131І thyroid dose may reflect a gradual increase of sporadic PTCs frequency in the potentially radiogenic series with time elapsed since accident. The frequency of oncocytic insensitive to radioiodine therapy of lymph node metastases recurrences also increased with patients age and OCh availability in primary PTC.

[The analysis of dynamics and structure of mortality of female and male population of reproductive age in the Republic of Chuvashia].

Reducing mortality of working-age population is a potential reserve for preserving Russia's population and its labor force. In addition, the task of analyzing health of economically active citizens of our country is inextricably linked with the challenge of developing strategy of development of reproductive potential at the regional level. As reproductive or generative woman's age is defined precisely enough, and such unambiguous definition for men is lacking, the study used mortality rates, calculated for men and women of working age (16 - 59 years and 16 - 54 years respectively) and officially published by the Russian Federal State Statistics Service (Rosstat) as characteristics of reproductive health. The analysis of mortality rate for working age men and women in the Republic of Chuvashia as well as the structure of main causes of death are presented for 2002-2016 in comparison with average indicators for the Russian Federation. The mortality rate of the mentioned population category in Republic of Chuvashia since 2002 has decreased by 17.5% in all age groups except women aged 30-39 years. At this, the rate of mortality decreased in men during the analyzed period is higher than in women i.e. 20.5% and 19.3% respectively. As compared with 2002, the percentage of circulatory system diseases, neoplasms, digestive system diseases increased with a simultaneous decrease in the proportion of "external" causes in mortality structure of able-bodied population of the Republic of Chuvashia in 2016. Throughout the analyzed period relative mortality rates of able-bodied men are four times and higher than those of women. The analysis of dynamics characteristics in mortality level and structure among working age women and men as well as risk factors that contribute to its growth, can become the basis for developing an organizational improvement program of rendering medical care to economically active population as a component of regional strategy of increasing the level of reproductive potential.

MORPHOLOGICAL CHARACTERISTICS OF CHRONIC GASTRODUODENITIS IN ADOLESCENTS WITH FOOD HYPERSENSITIVITY.

The aim of our work was to evaluate the morphological features of the mucous membrane of the stomach and duodenum in children with chronic diseases of the gastroduodenal zone on the background of food hypersensitivity. Morphological study was conducted for 50 adolescents aged 12 to 17 years who were in inpatient treatment in the gastroenterology department. In order to verify the diagnosis, all children were checked by fibroesophagogastroduodenoscopy of the upper digestive tract with biopsy of the mucous membrane of the stomach antrum and the descending part of the duodenum. Bioptates were stained by hematoxylin-eosin, Van Gieson and performed on light microscope. The results of the research of the mucous membrane of the stomach and duodenum show that adolescents with chronic gastroduodenitis and food hypersensitivity have 17 times higher risk of developing atrophy of duodenal mucous membrane, 11 times higher frequency of eosinophilic infiltration and 3 times higher incidence of mucous membrane fibrosis in the duodenum.

CLIP2 as radiation biomarker in papillary thyroid carcinoma.

A substantial increase in papillary thyroid carcinoma (PTC) among children exposed to the radioiodine fallout has been one of the main consequences of the Chernobyl reactor accident. Recently, the investigation of PTCs from a cohort of young patients exposed to the post-Chernobyl radioiodine fallout at very young age and a matched nonexposed control group revealed a radiation-specific DNA copy number gain on chromosomal band 7q11.23 and the radiation-associated mRNA overexpression of CLIP2. In this study, we investigated the potential role of CLIP2 as a radiation marker to be used for the individual classification of PTCs into CLIP2-positive and -negative cases-a prerequisite for the integration of CLIP2 into epidemiological modelling of the risk of radiation-induced PTC. We were able to validate the radiation-associated CLIP2 overexpression at the protein level by immunohistochemistry (IHC) followed by relative quantification using digital image analysis software (P=0.0149). Furthermore, we developed a standardized workflow for the determination of CLIP2-positive and -negative cases that combines visual CLIP2 IHC scoring and CLIP2 genomic copy number status. In addition to the discovery cohort (n=33), two independent validation cohorts of PTCs (n=115) were investigated. High sensitivity and specificity rates for all three investigated cohorts were obtained, demonstrating robustness of the developed workflow. To analyse the function of CLIP2 in radiation-associated PTC, the CLIP2 gene regulatory network was reconstructed using global mRNA expression data from PTC patient samples. The genes comprising the first neighbourhood of CLIP2 (BAG2, CHST3, KIF3C, NEURL1, PPIL3 and RGS4) suggest the involvement of CLIP2 in the fundamental carcinogenic processes including apoptosis, mitogen-activated protein kinase signalling and genomic instability. In our study, we successfully developed and independently validated a workflow for the typing of PTC clinical samples into CLIP2-positive and CLIP2-negative and provided first insights into the CLIP2 interactome in the context of radiation-associated PTC.

[Endocytic pathway of alpha-fetoprotein in mice bone marrow hematopoietic stem cells: molecular characterization and role in biological activity modification].

Endocytic pathway of alpha-fetoprotein (AFP) in three different, by the degree of maturity, types of the mouse bone marrow hematopoietic stem cells (HSC) is similar in its nature: it was based on the receptor-mediated transport through the membrane p60, p65 and p305 AFP receptors with clathrin-dependent mechanism of receptorosome organization, in the formation and generation of which AP-2 complex, endophilin, and dynamin are involved. In the studied types of HSCs, the non-degraded AFP was detected in Golgi complex through the formed receptorosome merging with it, as well as in the cytoplasm, endoplasmic reticulum, and mitochondria, presumably through sequential binding to the cytoplasmic distributor proteins--p55, p52, p62 and p67 AFP receptors, and also to transorganelle transporter proteins--p147 and p182 AFP receptors. The investigation of the role of AFP endocytosis in changing the biological activity of the studied types of HSCs has shown that it directly regulated the protein synthesis and metabolic activity, while its effect on other examined types of biological activity was mediated by ERK1/2.

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

BACKGROUND: A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. METHODS: We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. RESULTS: Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. CONCLUSION: The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

Reconstruction of individual thyroid doses to the Ukrainian subjects enrolled in the Chernobyl Tissue Bank.

The Chernobyl Tissue Bank (CTB) is an organisation that collects and stores samples of tumoral thyroid tissue obtained from Ukrainian and Russian subjects who were treated surgically for a thyroid cancer and had been exposed to (131)I from the Chernobyl accident. By 2012, the CTB had collected specimens of thyroid tissue from 2267 residents of Ukraine for the purpose of radiation research. Arithmetic mean thyroid doses and uncertainties have been estimated for all but 24 subjects for whom residence at the time of exposure was not found. The subjects have been classified into six groups or sub-groups according to the type of dosimetry-related information that is available for each of them. Excluding the 325 subjects with negligible radiation exposure, the arithmetic mean of the thyroid dose over all subjects is estimated as 0.4 Gy, with individual values ranging from <1 mGy to 13 Gy. The uncertainties in the individual thyroid dose estimates, characterised by the geometric standard deviations of their probability distributions, range from 1.3 to 8.7, with an arithmetic mean of 3.2.

[Oxidation of gold-antimony ores by a thermoacidophilic microbial consortium].

Antimony leaching from sulfide ore samples by an experimental consortium of thermoacidophilic microorganisms, including Sulfobacillus, Leptospirillum, and Ferroplasma strains was studied. The ores differed significantly in the content of the major metal sulfides (%): Sb(S), 0.84 to 29.95; Fe(S), 0.47 to 2.5, and As(S), 0.01 to 0.4. Independent on the Sb(S) concentration in the experimental sample, after adaptation to a specific ore and pulp compaction the microorganisms grew actively and leached/oxidized all gold-antimony ores at 39 ± 1 degrees C. The lower was the content of iron and arsenic sulfides, the higher was antimony leaching. For the first time the investigations conducted with the use of X-ray microanalysis research made it possible to conclude that in a natural high-antimony ore Sb inhibits growth of only a part of the cell population and that Ca, Fe, and Sb may compete for the binding centers of the cell.

A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas.

BACKGROUND: Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts. METHODS: Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to ¹³¹I. RESULTS: A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation. CONCLUSION: Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.

The Chernobyl thyroid cancer experience: pathology.

The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in the areas exposed to high levels of fallout. The Chernobyl Tumor Bank was set up in 1998 to make tumours available for study internationally, and a pathology panel reviewed all the tumours and established an agreed diagnosis. The thyroid tumours that were discovered after the Chernobyl nuclear accident were virtually all (95%) of the papillary carcinoma type. Rare examples of other tumour types were identified. Within the papillary group, several subtypes were noted, including classical or usual type, follicular variant, solid variant and mixed patterns Diffuse sclerosis variant, cribriform/morular type and Warthin-like variant were rare. No tall cell or columnar cell variants were identified. The tumours examined by the Pathology Panel of the Chernobyl Tumor Bank constitute a large representative sample (estimated at about 50%) of the tumours that developed in this population. This overview describes the method adopted by the panel and the different diagnostic categories adopted; illustrates the pathology of these neoplasms; compares the pathological characteristics of the early lesions with those identified after long latency periods and the institution of screening programmes and outlines the possible associated causes for the various morphological patterns seen.

The Chernobyl accident and its consequences.

The accident at the Chernobyl nuclear power plant was the worst industrial accident of the last century that involved radiation. The unprecedented release of multiple different radioisotopes led to radioactive contamination of large areas surrounding the accident site. The exposure of the residents of these areas was varied and therefore the consequences for health and radioecology could not be reliably estimated quickly. Even though some studies have now been ongoing for 25 years and have provided a better understanding of the situation, these are yet neither complete nor comprehensive enough to determine the long-term risk. A true assessment can only be provided after following the observed population for their natural lifespan. Here we review the technical aspects of the accident and provide relevant information on radioactive releases that resulted in exposure of this large population to radiation. A number of different groups of people were exposed to radiation: workers involved in the initial clean-up response, and members of the general population who were either evacuated from the settlements in the Chernobyl nuclear power plant vicinity shortly after the accident, or continued to live in the affected territories of Belarus, Russia and Ukraine. Through domestic efforts and extensive international co-operation, essential information on radiation dose and health status for this population has been collected. This has permitted the identification of high-risk groups and the use of more specialised means of collecting information, diagnosis, treatment and follow-up. Because radiation-associated thyroid cancer is one of the major health consequences of the Chernobyl accident, a particular emphasis is placed on this malignancy. The initial epidemiological studies are reviewed, as are the most significant studies and/or aid programmes in the three affected countries.

Radiation induced thyroid cancer: fundamental and applied aspects.

AIM: To describe the epidemiology and pathology of thyroid cancer in Ukraine, and to perform the molecular analysis of genetic alterations more frequently found to be associated to papillary carcinomas (PTC) in a selected group of PTC. MATERIALS AND METHODS: Relationship between the thyroid cancer incidence and gender, age, and place of residence of subjects aged 0-18 years at the time of the Chernobyl accident (5427 subjects of thyroid cancer, among which 3996 (73.6%) were children aged 0 to 14 years at the time of the accident, and 1431 (26.3%) were adolescents aged 15 to 18 years was studied. Pathologically analyzed thyroid carcinomas were obtained from 640 patients (20-40 years old at the time of surgery and born before the Chernobyl accident), and from 90 patients (11-22 years old at the time of surgery and born after the accident). All patients were operated during 2006-2008. RET/PTC rearrangements and BRAF(V600E) mutation were analyzed in 35 cases of PTC. RESULTS: A comparison between the thyroid cancer incidence rates in the 6 highest contaminated regions of Ukraine and in the other 21 regions shows the most significant difference between the rates for the last three years of follow-up, which confirms that a direct relationship is still present between the rise in thyroid cancer incidence and the post Chernobyl radiation exposure. Much lower incidence of thyroid cancer in subjects, who were born after the accident, additionally confirmed a direct relationship between the Chernobyl accident and thyroid cancer development at least in those who were aged up to 18 years at the time of the nuclear accident. Pathological results showed that with increasing latency the decrease has been noted in the percentage of PTC with solid structure, a decrease in invasive properties of tumors, as well as an increase in the percentage of PTC with papillary-follicular structure, encapsulated forms, and <> carcinomas measuring up to 1 cm. Molecular-biological studies of PTC revealed more common RET/PTC1 and RET/PTC3 rearrangements (34.3% of cases), than BRAFV600E mutation (24%cases). CONCLUSION: After 22 years from the Chernobyl nuclear accident the number and incidence of thyroid cancer cases in Ukraine was steadily increased in the cohort of those who were children and adolescents at the time of the accident. Most common thyroid tumors (PTC) were characterized by significant changes in histological structure with increasing latency. PTC with any RET/PTC rearrangements had more aggressive behavior than BRAF(V600E)-positive tumors or PTC without gene alterations.

[Analysis of the expression of RET/PTC oncogenes in post-chernobyl papillary thyroid carcinomas of patients from different age groups].

A comparative analysis of the expression of both, RET/PTC1 and RET/PTC3 oncogenes in papillary thyroid carcinomas (PTC) of patients from different age groups was carried out. Those were the following groups: children (mean age - 13 years, mean latency period - 13 years), young adults (mean age - 24 years, mean latency period - 14 years), adults (mean age - 38 years, mean latency period - 22 years). The presence of RET/PTC oncogenes was detected using polymerase chain reaction. In all cases the samples of both tumor and normal thyroid tissue were studied. It was established that induction of both, RET/PTC1 and RET/PTC3 rearrangements was present only in carcinoma samples. In PTCs the percentage of RET/PTC-positive tumors with increasing the age of patients has been decreasing. It should be noted that the part of carcinomas with induction of RET/PTC1 did not change with increasing the age of patients. At the same time the frequency of RET/PTC3 rearrangements with the increasing both the latency period and age of patients, significantly decreased. In conclusion, our data can evidence for the presence of correlation between the age of patients, latency period and induction of RET/PTC3 oncogenes.

A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to iodine-131 from Chernobyl fallout.

BACKGROUND: Like stable iodine, radioiodines concentrate in the thyroid gland, increasing thyroid cancer risk in exposed children. Data on exposure to the embryonic/fetal thyroid are rare, raising questions about use of iodine 131 (I-131) in pregnant women. We present here estimated risks of thyroid disease from exposure in utero to I-131 fallout from the Chernobyl nuclear accident. METHODS: We conducted a cross-sectional thyroid screening study (palpation, ultrasound, thyroid hormones, and, if indicated, fine needle aspiration) from 2003 to 2006. Participants were 2582 mother-child pairs from Ukraine in which the mother had been pregnant at the time of the accident on April 26, 1986, or 2 months after the time during which I-131 fallout was still present (1494 from contaminated areas, 1088 in the comparison group). Individual cumulative in utero thyroid dose estimates were derived from estimated I-131 activity in the mother's thyroid (mean 72 mGy; range 0-3230 mGy). RESULTS: There were seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm identified as a result of the screening. Whereas the estimated excess odds ratio per gray for thyroid carcinoma was elevated (excess odds ratio per gray 11.66), it was not statistically significant (P = 0.12). No radiation risks were identified for other thyroid diseases. CONCLUSION: Our results suggest that in utero exposure to radioiodines may have increased the risk of thyroid carcinoma approximately 20 yr after the Chernobyl accident, supporting a conservative approach to medical uses of I-131 during pregnancy.

[Genotypic and phenotypic polymorphism of environmental strains of the moderately thermophilic bacterium Sulfobacillus sibiricus].

Five cultures of moderately thermophilic spore-forming acidophilic chemolithotrophic bacteria were isolated from the zones of spontaneous heating of pyrrhotine-containing pyrite-arsenopyrite gold-arsenic sulfide ores in an operating open pit (strains B1, B2, B3, OFO, and SSO). Analysis of the chromosomal DNA structure revealed differences between these cultures at the strain level (apart from B3 and SSO, which had identical restriction profiles). All the strains had a similar G + C DNA molar content (47.4-48.3%). The level of DNA reassociation was 85 to 95%. The similarity between the DNA of the type strain Sulfobacillus sibiricus N1 isolated from arsenopyrite ore concentrate and that of these strains (83-93%) indicates that they belong to the same species. The strains had similar values of pH and temperature optimal for growth on ferrous iron (1.6-2.0 and 45-55 degrees C, respectively). They were mixotrophs; Fe(II), S0, and sulfide minerals along with organic compounds were used as energy sources and electron donors. However, the kinetic parameters of growth and substrate oxidation varied from strain to strain. Genetic variety of the strains from diverse ecosystems and environments is possibly the result of the different rates of microevolution processes.

Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC.

The aim of this study is to investigate additional genetic alterations in papillary thyroid carcinomas (PTCs) with known RET/PTC rearrangements. We applied array-based comparative genomic hybridization (array CGH) to 33 PTC (20 PTC from adults, 13 post-Chernobyl PTC from children) with known RET/PTC status. Principal component analysis and hierarchical cluster analysis identified cases with similar aberration patterns. Significant deviations between tumour-groups were obtained by statistical testing (Fisher's exact test in combination with Benjamini-Hochberg FDR-controlling procedure). FISH analysis on FFPE sections was applied to validate the array CGH data. Deletions were found more frequently in RET/PTC-positive and RET/PTC-negative tumours than amplifications. Specific aberration signatures were identified that discriminated between RET/PTC-positive and RET/PTC-negative cases (aberrations on chromosomes 1p, 3q, 4p, 7p, 9p/q, 10q, 12q, 13q and 21q). In addition, childhood and adult RET/PTC-positive cases differ significantly for a deletion on the distal part of chromosome 1p. There are additional alterations in RET/PTC-positive tumours, which may act as modifiers of RET activation. In contrast, alterations in RET/PTC-negative tumours indicate alternative routes of tumour development. The data presented serve as a starting point for further studies on gene expression and function of genes identified in this study.

[Phenotypic properties of Sulfobacillus thermotolerans: comparative aspects].

The phenotypic characteristics of the species Sulfobacillus thermotolerans Kr1(T), as dependent on the cultivation conditions, are described in detail. High growth rates (0.22-0.30 h(-1)) and high oxidative activity were recorded under optimum mixotrophic conditions at 40 degrees C on medium with inorganic (Fe(II), S(0), or pyrite-arsenopyrite concentrate) and organic (glucose and/or yeast extract) substrates. In cells grown under optimum conditions on medium with iron, hemes a, b, and, most probably, c were present, indicating the presence of the corresponding cytochromes. Peculiar extended structures in the form of cylindrical cords, never observed previously, were revealed; a mucous matrix, likely of polysaccharide nature, occurred around the cells. In the cells of sulfobacilli grown litho-, organo-, and mixotrophically at 40 degrees C, the enzymes of the three main pathways of carbon utilization and some enzymes of the TCA cycle were revealed. The enzyme activity was maximum under mixotrophic growth conditions. The growth rate in the regions of limiting temperatures (55 degrees C and 12-14 degrees C) decreased two- and tenfold, respectively; no activity of 6-phosphogluconate dehydrogenase, one of the key enzymes of the oxidative pentose phosphate pathway, could be revealed; and a decrease in the activity of almost all enzymes of glucose metabolism and of the TCA cycle was observed. The rate of 14CO2 fixation by cells under auto-, mixo-, and heterotrophic conditions constituted 31.8, 23.3, and 10.3 nmol/(h mg protein), respectively. The activities of RuBP carboxylase (it peaked during lithotrophic growth) and of carboxylases of heterotrophic carbon dioxide fixation were recorded. The physiological and biochemical peculiarities of the thermotolerant sulfobacillus are compared versus moderately thermophilic sulfobacilli.

Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers.

Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, gamma-radiation and H(2)O(2). On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to gamma-radiation and H(2)O(2) are similar. On a finer scale, a 118 genes signature discriminated the gamma-radiation and H(2)O(2) responses. This signature could be used to classify the tumours as CTB or French with an error of 15-27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to gamma-radiation and H(2)O(2). These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test.

Gene expression and the biological phenotype of papillary thyroid carcinomas.

The purpose of this paper is to correlate the molecular phenotype of papillary thyroid carcinoma (PTC) to their biological pathology. We hybridized 26 PTC on microarrays and showed that nearly 44% of the transcriptome was regulated in these tumors. We then combined our data set with two published PTC microarray studies to produce a platform- and study-independent list of PTC-associated genes. We further confirmed the mRNA regulation of 15 genes from this list by quantitative reverse transcription-PCR. Analysis of this list with statistical tools led to several conclusions: (1) there is a change in cell population with an increased expression of genes involved in the immune response, reflecting lymphocyte infiltration in the tumor compared to the normal tissue. (2) The c-jun N-terminal kinase pathway is activated by overexpression of its components. (3) The activation of ERKK1/2 by genetic alterations is supplemented by activation of the epidermal growth factor but not of the insulin-like growth factor signaling pathway. (4) There is a downregulation of immediate early genes. (5) We observed an overexpression of many proteases in accordance with tumor remodeling, and suggested a probable role of S100 proteins and annexin A2 in this process. (6) Numerous overexpressed genes favor the hypothesis of a collective migration mode of tumor cells.