NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis?

BACKGROUND AND AIMS: High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices. Our aim was to establish if p53/Rb1 immunohistochemical status in GI-NENs with Ki67 index >20% can predict the histopathological diagnosis. METHODS: p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis. RESULTS: The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, <1%), T (tumor, 1%-20%) and C (carcinoma, >20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p<0.001, χ 2 =27.017). NET G3s showed positive expression for Rb1; 73.08% of NECs expressed negative Rb1 (p<0.001, χ 2 =21.351). NECs and NEC components in MiNENs showed Rb1 mutational status in 13 C cases (13/19, 68.42%), 4 N cases (4/5, 80%) and in both the T cases (p=0.002, χ 2 =11.187). CONCLUSIONS: Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.

Umbilical Cord Teratoma - A Short Case Report.

Background: Teratomas can occur in the umbilical cord, and may or may not be associated with other congenital abnormalities. Case report: This 35-year-old primigravida gave birth 37-38 weeks to a 3290-g normal female. The umbilical cord, at 10 cm from the abdominal insertion, had an 8 cm mature teratoma. Work-up revealed no other abnormalities. Discussion: Mature teratomas may occur in the umbilical cord, and may or may not have additional clinical sequalae.

VARIATION OF INDOOR RADON CONCENTRATION WITHIN A RESIDENTIAL COMPLEX.

A recent challenge in research dedicated to residential exposure to radon comes from the growing number of houses retrofitted to reduce energy consumption. Efficiently insulated buildings and modern architectural solutions can lead to the accumulation of high levels of indoor pollutants. A systematic analysis was conducted in a residential complex (consisting of six houses) in order to assess the annual radon concentration and to evaluate the intensity of the relationships with various factors, such as the indoor-outdoor temperature differences, wind speed and wind direction. Three types of occupational behaviour, influencing the ventilation rate of the dwellings and, implicitly, the indoor radon activity concentration were observed. By calculating the partial correlation coefficient between the radon concentration and the wind direction, with the wind speed as the control variable, for all six houses the correlation coefficient presents negative values.

A COMPREHENSIVE STUDY OF RESIDENTIAL, GEOGENIC AND WATER RADON IN THE NORTH AREA OF MURES COUNTY, ROMANIA.

This study presents results of a complex survey about residential, soil and water radon in the North of Mures county (Romania). Indoor radon measurements were performed by using CR-39 track detectors, while radon concentrations in soil and in water were measured by using the LUK3C device and accessories. The indoor radon concentrations of 157 houses ranged from 9 to 414 Bq m-3, with an arithmetic mean of 131 Bq m-3 and a geometric mean of 105 Bq m-3. In ~3.2% of the investigated houses exceed the recommended reference level of 300 Bq m-3. The soil gas radon concentrations in 137 sampling points varied from 5.0 to 88.0 kBq m-3, with a geometric mean of 14.6 kBq m-3. Results of 190 water samples shows radon concentrations from 0.2 to 28.0 Bq L-1, with a geometric mean of 5.0 Bq L-1. Beside these results, indoor, soil and water radon maps were performed, divided into cells of 5 km × 5 km.

Radon levels in Romanian caves: an occupational exposure survey.

A comprehensive radon survey has been carried out in seven caves located in the western half of Romania's most significant karst regions. Touristic and non-touristic caves were investigated with the aim to provide a reliable distribution of their radon levels and evaluate the occupational exposure and associated effective doses. Radon gas concentrations were measured with long-term diffusion-type detectors during two consecutive seasons (warm and cold). All investigated caves exceed the European Union reference level of radon gas at workplaces (300 Bq/m3). The radon concentration in these caves ranges between 53 and 2866 Bq/m3, reflecting particular cave topography, season-related cave ventilation, and complex tectonic and geological settings surrounding each location. Relatively homogeneous high radon levels occur in all investigated touristic caves and in Tausoare and Vântului along their main galleries. Except for Muierii, in all the other caves radon levels are higher during the warm season, compared to the cold one. This suggests that natural cave ventilation largely controls the underground accumulation of radon. The results reported here reveal that the occupational exposure in Ursilor, Vadu Crisului, Tausoare, Vântului, and Muierii caves needs to be carefully monitored. The effective doses to workers vary between an average of 0.25 and 4.39 mSv/year depending on the measuring season. The highest values were recorded in show caves, ranging from 1.15 to 6.15 mSv/year, well above the European recommended limit, thus posing a potential health hazard upon cave guides, cavers, and scientists.

Residential, soil and water radon surveys in north-western part of Romania.

The exposure to radon and radon decay products in homes and at workplaces represents the greatest risk from natural ionizing radiation. The present study brings forward the residential, soil and water radon surveys in 5 counties of Romania. Indoor radon measurements were performed by using CR-39 track detectors exposed for 3 months on ground-floor level of dwellings, according to the NRPB Measurements Protocol. Radon concentrations in soil and water were measured using the LUK3C device. The indoor radon concentrations ranged from 5 to 2592 Bq⋅m-3 with an updated preliminary arithmetic mean of 133 Bq⋅m-3, and a geometric mean of 90 Bq⋅m-3. In about 6% of the investigated grid cells the indoor radon concentrations exceed the threshold of 300 Bq⋅m-3. The soil gas radon concentration varies from 0.8 to 169 kBq⋅m-3, with a geometric mean of 28.4 kBq⋅m-3. For water samples, the results show radon concentrations within the range of 0.3-352 kBq⋅m-3 with a geometric mean of 7.7 Bq⋅L-1. The indoor radon map was plotted on a reference grid developed by JRC with the resolution 10 × 10 km2.

Testing radon mitigation techniques in a pilot house from Baita-Stei radon prone area (Romania).

This work presents the implementation and testing of several radon mitigation techniques in a pilot house in the radon prone area of Baita-Stei in NW part of Romania. Radon diagnostic investigations in the pilot house showed that the main source of radon was the building sub-soil and the soil near the house. The applied techniques were based on the depressurization and pressurization of the building sub-soil, on the combination of the soil depressurization system by an electric and an eolian fans. Also, there was made an application of a radon barrier membrane and a testing by the combination of the radon membrane by the soil depressurization system. Finally, the better obtained remedial efficiency was about 85%.

Radon concentration in drinking water and supplementary exposure in Baita-Stei mining area, Bihor county (Romania).

The radon concentration was measured in the drinking water of public water supply and private wells located in the mining area of BaiTa-Stei, Bihor County, Romania. The measurements were performed using the LUK-VR system based on radon gas measurement with Lucas cell. The results show that the radon concentrations are within the range of 1.9-134.3 kBq m(-3) with an average value of 35.5 kBq m(-3) for well water, 18.5 kBq m(-3) for spring water and 6.9 kBq m(-3) for tap water. Comparing with previous data from the whole of Transylvania, the average value is two times higher, proving this zone to be a radon-prone area. From the results of this study the effective dose to the population is between 4.78 and 338.43 µSv y(-1). These doses are within the recommended limits of the world organisations.

Soil and building material as main sources of indoor radon in Baita-Stei radon prone area (Romania).

Radon contributes to over than 50% of the natural radiation dose received by people. In radon risk areas this contribution can be as high as 90-95%, leading to an exposure to natural radiation 5-10 times higher than normal. This work presents results from radon measurements (indoor, soil and exhalation from building materials) in Baita-Stei, a former uranium exploitation area in NW Romania. In this region, indoor radon concentrations found were as high as 5000 Bq m(-3) and soil radon levels ranged from 20 to 500 kBq m(-3). An important contribution from building materials to indoor radon was also observed. Our results indicate two independent sources of indoor radon in the surveyed houses of this region. One source is coming from the soil and regular building materials, and the second source being uranium waste and local radium reached material used in building construction. The soil as source of indoor radon shows high radon potential in 80% of the investigated area. Some local building materials reveal high radon exhalation rate (up to 80 mBq kg(-1) h(-1) from a sandy-gravel material, ten times higher than normal material). These measurements were used for the radon risk classification of this area by combining the radon potential of the soil with the additional component from building materials. Our results indicate that Baita-Stei area can be categorized as a radon prone area.

Thorough investigations on indoor radon in Baita radon-prone area (Romania).

A comprehensive radon survey has been carried out in Baita radon-prone area, Transylvania, Romania, in 4 localities (Baita, Nucet, Fînate, and Cîmpani) situated in the vicinity of former Romanian uranium mines. Indoor radon concentrations have been measured in 1128 ground floor rooms and cellars of 303 family houses by using CR-39 diffusion type radon detectors. The annual average of indoor radon concentration for Baita area was found to be 241±178 Bq m(-3), which is about two times higher than the average value of 126 Bq m(-3), computed for Romania. About 28% of investigated houses exceed the reference level of radon gas in dwellings of 300 Bq m(-3). The indoor radon measurements on each house have been carried out in several rooms simultaneously with the aim of obtaining a more detailed picture on the exposure to radon in the studied area. An analysis on the variability of radon levels among floors (floor-to-floor variation) and rooms (room-to-room variation) and also the influence of factors like the presence of cellar or the age of the building is presented. The coefficient of variation (CV) within ground floor rooms of the same house (room-to-room variation) ranged between 0.9 and 120.8%, with an arithmetic mean of 46.2%, a large variability among rooms within surveyed dwellings being clearly identified. The mean radon concentration in bedrooms without cellar was higher than in bedrooms above the cellar, the difference being statistically significant (t test, one tail, p<0.001, n=82). For houses built during 1960-1970 an increasing trend for radon levels was observed, but overall there was no significant difference in indoor radon concentrations by age of dwelling (one-way ANOVA test, p>0.05).

Preliminary lung cancer risk assessment of exposure to radon progeny for Transylvania, Romania.

The objective of the present study was to assess the lung cancer risk induced by exposures to radon progeny of people living in some areas of Transylvania, Romania. Indoor radon concentrations were measured in 667 dwellings of Stei area, Cluj, Bistrita-Nasaud, Sibiu, and Alba counties. Measurements were performed using CR-39 track detectors, exposed for a minimum of 3 mo. Average annual radon concentrations were 232, 114, 71, 62, and 161 Bq m for Stei area, Cluj, Bistrita-Nasaud, Sibiu, and Alba, respectively. The linear risk model of Darby was used to simulate the dose-effect relationship and relative lung cancer risk at low doses of alpha particles specific to residential radon exposures. Predicted relative risks at the measured exposure levels, together with information on the total number of reported lung cancer deaths and the number of people living in these regions, enabled us to estimate the fraction of lung cancer cases in each area that is attributable to radon. These percentages are 16.67% for Stei area, 9.09% for Cluj, 5.66% for Bistrita-Nasaud, 4.76% for Sibiu, and 12.28% for Alba county among lifetime non-smokers. Assuming that the smoking rates are similar for the investigated regions (10.72% smokers among men and 5.95% among women), around 64 to 69% of the total number of annual lung cancer deaths, stratified by sex, would be attributed to radon and occur among smoking male population, and around 35 to 44% would be attributed to radon and occur among smoking female population.

Preliminary integrated indoor radon measurements in Transylvania (Romania).

Measurements of indoor radon concentrations were performed in 406 residential houses in five counties (Cluj, Bihor, Alba, Bistrita, and Sibiu) using Makrofol and CR-39 alpha-track detectors. From our measurements, an average indoor radon concentration of 82.5 Bq m(-3) for the Transylvanian population was calculated, i.e. an annual effective dose of 2.4 mSv for the whole body. The calculated dose is 62% higher than that previously reported but yet below the recommended action level of ICRP (International Commission on Radiological Protection). A log-normal distribution of the radon concentration was obtained for the studied counties, excluding some higher values from the Stei region--a radon-prone area in Transylvania. For the Stei region, the data show a dual log-normal distribution of the radon concentration with the second maximum being related to the houses built using uranium waste as a construction material. Assuming a cancer risk coefficient of 10(-4)/100 Bq m(-3) year(-1), one can estimate that about 600 lung cancer per year, for about 7,000,000 inhabitants of the Transylvania region, are due to radon inhalation.

Comparative risk assessment of residential radon exposures in two radon-prone areas, Stei (Romania) and Torrelodones (Spain).

Radon and radon progeny are present indoors, in houses and others dwellings, representing the most important contribution to dose from natural sources of radiation. Most studies have demonstrated an increased risk of lung cancer at high concentration of radon for both smokers and nonsmokers. The work presents a comparative analysis of the radon exposure data in the two radon-prone areas, Stei, Transylvania, (Romania), in the near of old Romanian uranium mines and in the granitic area of Torrelodones town, Sierra de Guadarrama (Spain). Measurements of indoor radon were performed in 280 dwellings (Romania) and 91 dwellings (Spain) by using nuclear track detectors, CR 39. The highest value measured in Stei area was 2650 Bq m(-3) and 366 Bq m(-3) in the Spanish region. The results are computed with the BEIR VI report estimates using the age-duration model at an exposure rate below 2650 Bq m(-3). We used the EC Radon Software to calculate the lifetime lung cancer death risks for individuals groups in function of attained age, radon exposures and tobacco consumption. A total of 233 lung cancer deaths were observed in the Stei area for a period of 13 years (1994-2006), which is 116.82% higher than expected from the national statistics. In addition, the number of deaths estimated for the year 2005 is 28, which is worth more than 2.21 times the amount expected by authorities. In comparison, for Torrelodones was rated a number of 276 deaths caused by lung cancer for a period of 13 years, which is 2.09 times higher than the number expected by authorities. For the year 2005 in the Spanish region were reported 32 deaths caused by pulmonary cancer, the number of deaths exceeding seen again with a factor of 2.10 statistical expectations. This represents a significantly evidence that elevated risk can strongly be associated with cumulated radon exposure.