Association between PD-L1 Expression and the Prognosis and Clinicopathologic Features of Non-Clear Cell Renal Cell Carcinoma.

PD-L1 is one of the two programmed cell death 1 (PD-1) ligands and a part of an immune checkpoint system (PD-1/PD-L1) with widespread clinical application. The aim of this study was to investigate PD-L1 expression and its association with clinicopathological and prognostic significance in non-clear cell renal cell carcinoma (non-ccRCC) patients. A total of 41 papillary (pRCC) and 20 chromophobe (chRCC) RCC tumors were examined for PD-L1 expression by immunohistochemistry in the cancer cells and tumor-infiltrating mononuclear cells (TIMCs). PD-L1 positivity was detected in 36.6% pRCC and 85.0% chRCC cancer cells, while PD-L1 positivity was observed in 73.2% pRCC and 50.0% chRCC TIMCs. PD-L1 positivity in both pRCC and chRCC tumor cells was not correlated with any of the examined clinicopathological features, while PD-L1 positivity in TIMCs was associated with the age of patients with pRCC. During follow-up, the death was documented among 6 patients with pRCC. Papillary RCC patients with PD-L1-positive tumor cells were significantly associated with an increased risk of death compared with patients with PD-L1-negative cancer cells. A similar trend was observed when comparing PD-L1 expression in TIMCs. However, no differences in overall survival for PD-L1-positive pRCC patients with compared to PD-L1-negative patients were observed in tumor cells or TIMCs.

Impaired Functional Status Increases Fracture Incidence in 10-year Follow-Up: The Results from RAC-OST-POL Study.

INTRODUCTION: The aim of study was to establish the influence of baseline functional status on fracture incidence. METHODOLOGY: In a prospective 10-years observation in epidemiological sample of postmenopausal women from RAC-OST-POL Study a thesis that affected functional status enhance fracture incidence was verified. At baseline, data were collected in 978 women at mean age 66.48±7.6 years and after 10 years of follow-up 640 subjects at mean age 75.04±6.95 years remained in the study. Functional status at baseline was established using Stand up and Go test (SAG) and Activity of Daily Living (IADL). Afterwards, annually data on fracture incidence were collected by phone interviews. RESULTS: In the period of observation 190 low-energy fractures in 129 women were noted. The whole group was divided into subgroups: without fracture (n=511), with one fracture (n=91) and those ones who had more than one fracture (n=38). In fractured and unfractured subgroup mean SAG results were 11.36±4.28 and 10.36±2.76, respectively and differed significantly (p<0.01). With increasing number of fractures the SAG time was longer - it was 11.15±4.49 in one fracture subgroup and 11.87±3.73 in multiple fractures subgroup, with both values significantly higher than in no fracture subjects. The mean value of IADL was 23.56±1.60. In 576 (90%) women IADL reached maximal value of 24 points. In the rest of them (n=64) IADL score was between 11 and 23 points. Mean value of IADL in fractured and unfractured subgroup were 23.27±1.97 and 23.64±1.47, respectively and differed significantly (p<0.01). CONCLUSION: The measures of functional status predict fractures in a prospective observation of representative epidemiological female sample.

Two Single Nucleotide Polymorphisms in the Von Hippel-Lindau Tumor Suppressor Gene in Patients with Clear Cell Renal Cell Carcinoma.

The most common subtype of renal cell carcinoma (RCC) is clear cell type (ccRCC), which accounts for approximately 75% of cases. von Hippel-Lindau (VHL) gene has been shown to be affected in more than half of ccRCC cases. Two single nucleotide polymorphisms (SNPs) located in VHL gene, rs779805 and rs1642742, are reported to be involved in the occurrence of ccRCC. The aim of this study was to assess their associations with clinicopathologic and immunohistochemical parameters, as well as risk and survival of ccRCC. The study population consisted of 129 patients. No significant differences in genotype or allele frequencies of VHL gene polymorphisms were observed between ccRCC cases and control population, and we have found that our results do not indicate a significant relationship of these SNPs with respect to ccRCC susceptibility. Additionally, we did not observe a significant association of these two SNPs with ccRCC survival. However, our results conclude that rs1642742 and rs779805 in the VHL gene are associated with increased tumor size, which is the most important prognostic indicator of renal cancer. Moreover, our analysis showed that patients with genotype AA of rs1642742 have a trend towards higher likelihood of developing ccRCC within their lifetime, while allele G of rs779805 can have a preventive effect against the development of renal cancer in stage 1. Therefore, these SNPs in VHL may be useful as genetic tumor markers for the molecular diagnostics for ccRCC patients.

Glucocorticoids Increase Fracture Risk and Fracture Prevalence Independently from Bone Mineral Density and Clinical Risk Factors: Results from the Gliwice Osteoporosis (GO) Study.

The aim of the study was to establish the influence of glucocorticoids (GC) on fracture risk, probability, and prevalence. A set of 1548 postmenopausal women were divided into study group - treated with GC (n=114, age 66.48±7.6 years) and controls (n=1434, age 66.46±6.83 years). Data on clinical risk factors for osteoporosis and fractures were collected. Hip bone densitometry was performed using a device Prodigy (GE, USA). Fracture probability was established by FRAX, and fracture risk by Garvan algorithm and POL-RISK. Fracture risk and fracture probability were significantly greater for GC-treated women in comparison to controls. In the study group, there were 24, 3, 24, and 6 fractures noted at spine, hip, forearm, and arm, respectively. The respective numbers of fractures reported in controls at those skeletal sites were: 186, 23, 240, and 25. The use of GCs increased significantly prevalence of all major, spine and arm fractures. Also the number of all fractures was affected by GC use. Following factors significantly increased fracture probability: age (OR 1.04 per each year; 95% CI: 1.03-1.06), GC use (OR 1.54; 95% CI: 1.03-2.31), falls (OR 2.09; 95% CI: 1.60-2.73), and FN T-score (OR 0.62 per each unit; 95% CI: 0.54-0.71). In conclusion, in patients treated with GCs the fracture risk, probability, and prevalence were increased. This effect was evident regardless of whether GC therapy is included in the algorithm as a risk factor (FRAX, POL-RISK) or not taken into consideration (Garvan nomogram).

The significance of height loss in postmenopausal women. The results from GO Study.

BACKGROUND: The aim of the study was the assessment of clinical significance of height loss (HL) in female population. MATERIAL: The study cohort was recruited from GO Study. Data from 1735 postmenopausal women aged over 55 years (mean age 68.15 ± 8.16 years) were analysed. METHODS: Data on clinical risk factors for osteoporosis and fractures were collected. Bone densitometry at hip was performed using a device Prodigy (GE, USA). Height was established using stadiometer and was compared with maximal height in early adulthood. RESULTS: The mean HL was 3.9 ± 3.2 cm. HL was significantly higher in women with fractures in comparison with those without fracture (4.9 ± 3.6 cm vs 3.4 ± 2.8 cm; P < .0001). HL increased with the number of fractures, and was 4.1 ± 3.2 cm, 5.3 ± 3.5 cm and 6.7 ± 4.1 cm in women with one, two and three or more fractures respectively. Women with spine fractures presented with HL higher in comparison with all the other subjects (6.3 ± 4.0 vs 3.6 ± 2.9 cm, P < .0001) and women with all non-spine fractures (6.3 ± 4.0 vs 4.0 ± 3.0 cm, P < .0001). In women with steroid use and falls, HL was significantly greater than in subjects without this factor. HL correlated significantly with age and BMI (positively) and current height (negatively). Mean T-score for FN BMD was -1.75 ± 0.9 and correlate significantly with HL (r = -.21, P < .0001). For the HL threshold above 4 cm, the fracture incidence was above 50%. CONCLUSION: Height loss value is a simple and very informative measure describing fracture risk and functional status in postmenopausal women. HL exceeding 4 cm is related to fracture probability above 50%.

Investigation of clinicopathological parameters and expression of COX-2, bcl-2, PCNA, and p53 in primary and recurrent sporadic odontogenic keratocysts.

OBJECTIVES: Odontogenic keratocyst (OKC) presents considerable variation in aggressiveness and propensity for recurrence, yet hitherto, no explicit clinicopathological features have been determined to clearly demonstrate the potential for relapse. This retrospective study aims to investigate the prognostic relevance of various clinicopathological features as well as immunoexpression of COX-2, bcl-2, PCNA, and p53 in sporadic OKC. MATERIALS AND METHODS: Among 41 patients with OKC treated by enucleation, the frequency of recurrence for various clinicopathological features as well as immunoexpression for COX-2, bcl-2, PCNA, and p53 was evaluated. RESULTS: The mean follow-up was 8.49 years, and recurrences were ascertained in 29.27% of cases. We found significant differences between recurrent and non-recurrent cysts in terms of multilocularity (P = 0.029), cortical perforation (P = 0.001), and lesion size (P < 0.001). Hazard risk for the recurrence was 3.362 (95% CI 1.066-10.598) for multilocular cysts, 7.801 (95% CI 2.1-28.985) for evidence of cortical perforation, and 1.004 (1.002-1.006) for 1 mm2 of lesion size on panoramic radiographs. We also found that immunoexpression of PCNA significantly correlates with the radiographic evidence of cortical perforation (P = 0.048) and that there is significant positive correlation between expression of COX-2 and bcl-2 (P = 0.001) as well as significant negative correlation between immunoexpression of COX-2 and age (P = 0.002). None of the other analyzed factors were associated with the recurrence. CONCLUSIONS: Larger size, multilocularity, and cortical perforation in sporadic OKC may be correlated with the relapse. CLINICAL RELEVANCE: Immunohistochemical analyses of COX-2, bcl-2, PCNA, and p53 lack prognostic utility in sporadic OKC.

Quantitative Ultrasound Measurement at the Hand Phalanges Does Not Reveal Skeletal Disturbances in Children With Bronchial Asthma: A Longitudinal Observation.

OBJECTIVES: To assess the skeletal status in asthmatic children treated with inhaled corticosteroids in a longitudinal observation by quantitative ultrasound (US) measurement at the hand phalanges. METHODS: Thirty-four children were studied prospectively. Quantitative US measurements were performed at baseline and after a mean ± SD of 2.35 ± 0.20 years. The obtained results were compared to age-, sex-, and body size-matched control participants selected from a database of previously examined healthy children. Individual changes in the amplitude-dependent speed of sound (Ad-SoS) during the follow-up period were also analyzed. RESULTS: The mean age of the asthmatic children was 10.6 ± 2.5 years. The mean Ad-SoS in the asthmatic children at baseline was 1940.5 ± 49.6 m/s, and the mean Z score was -0.26 ± 0.80. Corresponding values at the follow-up examination were 1976.2 ± 63.6 m/s and -0.18 ± 1.16. The results did not differ significantly in comparison to the healthy controls. The analysis of individual changes in Ad-SoS revealed that 18 participants had a significant increase in this parameter (ie, exceeding the least significant change threshold), and 16 did not have a significant change in their values. No one had a significant decrease in Ad-SoS. CONCLUSIONS: Quantitative US at the hand phalanges applied as a diagnostic tool revealed no essential differences in the pattern of skeletal development between asthmatic children treated with inhaled glucocorticosteroids and healthy controls.

Radon as a risk factor of lung cancer

Radon is the second leading cause of lung cancer after smoking. Indoor radon concentration poses a significant and potentially subject to the prevention risk factor of lung cancer development. The paper present the history of studies assessing occupational and indoor radon exposure and an impact of international organizations for raise public and political awareness about the consequences of long term exposure to residential radon, resulting in the European Directive 2013/59/Euratom of 5 December 2013 laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation.

Influence of education, marital status, occupation, and the place of living on skeletal status, fracture prevalence, and the course and effectiveness of osteoporotic therapy in women in the RAC-OST-POL Study.

The RAC-OST-POL population-based, epidemiological study provided data concerning the influence of education, marital status, occupation, and the place of living (residence) on skeletal status, fracture prevalence, and the course and effectiveness of osteoporotic therapy in 625 women older than 55 years, all of them recruited from the District of Raciborz in Poland. Their mean age was 66.4 ± 7.8 years. All the women completed a specially designed questionnaire. The skeletal status was assessed by femoral neck (FN) and total hip (TH) densitometry, using a Lunar DPX system (USA). In univariate analyses, taking into consideration the age differences, bone mineralization was dependent on marital status (Z score for FN and TH was significantly higher in widows than in divorcees; p < 0.05), place of residence (better results in rural areas; p < 0.05), and occupation (better in standing than sitting jobs; p < 0.05 for FN Z score and p < 0.01 for TH Z score). The multivariate model allowed us to verify that only place of living and type of occupation had a significant influence on densitometry results. In direct comparison, fracture prevalence seemed to be borderline significantly more common in widows (33.5%) and least common among divorcees (11.8%) (χ(2) = 6.9, df = 3, p = 0.07), but reanalysis performed after age adjustment excluded a true impact of marital status on fracture occurrence. Other factors did not affect fracture occurrence. Some factors influenced the use of medications for osteoporosis: higher level of education was associated with a more frequent use of vitamin D (χ(2) = 8.49, df = 3, p < 0.05) and of hormone replacement therapy (HRT) (χ(2) = 35.7, df = 3, p < 0.00001). HRT was most commonly used by unmarried women (30%) and least commonly by divorcees (11.8%) (χ(2) = 11.7, df = 3, p = 0.01). Vitamin D was more often used among women from the urban area of Raciborz than by those from surrounding rural areas (χ(2) = 9.2, df = 1, p < 0.01). The frequency of use of the three aforementioned medications was associated with the character of occupation. Women with sedentary jobs demonstrated the highest frequency of intake for vitamin D (χ(2) = 9.92, df = 3, p < 0.05) and HRT (χ(2) = 19.48, df = 3, p < 0.001) as well as for other antiresorptive medications (χ(2) = 8.18, df = 3, p < 0.05). We concluded that the results of the epidemiological study demonstrate that both skeletal status and use of antiosteoporotic medications were partially modified by analyzed social factors, whereas fracture prevalence was generally independent from those factors. These data suggest that education, marital status, place of living, and type of occupation may have impacts on implementation of osteoporosis-preventing health programs.

FRAX calculator and Garvan nomogram in male osteoporotic population.

PURPOSE: The aim of the study was the presentation of osteoporotic fracture prediction in men. METHODS: Eight-hundred and one men at the mean age of 70.8 ± 9.31 years were examined. The 10-year fracture prediction was established, using the FRAX calculator and Garvan nomogram. RESULTS: The mean value for any fracture and hip fracture probabilities for FRAX were 7.26 ± 5.4% and 3.68 ± 4.25%, respectively. For Garvan fracture, risk values were 26.44 ± 23.83% and 12.02 ± 18.1%. The mean conformity for any fracture and hip fracture prediction for threshold of 20% (any fracture) and 3% (hip fracture) between Garvan and FRAX values was 55.8% (κ 0.041) and 79.65% (κ 0.599), respectively. ROC analyses showed the following areas under the ROC curves (AUC) for any fractures: FRAX 0.808 and Garvan nomogram 0.843 (p = 0.059). The AUC values for hip fractures were 0.748 for Garvan nomogram and for 0.749 FRAX, and did not differ. On the base of ROC data, the cut-off values with best accuracy to predict fractures for both methods were established. The conformity between methods for thresholds indicated by ROC analysis was 72.5% (κ 0.435) for any and 77.7% (κ 0.543) for hip fractures. CONCLUSION: The conformities between FRAX and Garvan in regard to hip fracture prediction were acceptable for a threshold of 3% and thresholds derived by ROC analysis, while for any fracture we recommend to use thresholds established by ROC analysis. This may suggest that the use of "universal" cut-off points is probably misleading.

Calcium intake and osteoporosis: the influence of calcium intake from dairy products on hip bone mineral density and fracture incidence - a population-based study in women over 55 years of age.

OBJECTIVE: The incidence of osteoporosis increases with age and is most frequently observed in postmenopausal women. The objective of the present population-based cohort study was to assess the influence of Ca intake from dairy sources on hip bone mineral density and hip fracture incidence in a group of Polish women over 55 years of age. DESIGN: The main outcome measures included: bone mineral density, the number of previous fractures and the reported Ca intake from dairy sources, assessed by a diet questionnaire. SETTING: The RAC-OST-POL Study was conducted in the District of Raciborz in the south of Poland. SUBJECTS: The study was carried out in a group of 625 women, randomly recruited from the general population of women aged >55 years. RESULTS: Median Ca intake from dairy products was lower in the group of women with femoral neck T-score ≤-2·5 than in the group with T-score >-2·5 (275 v. 383 mg/d; P = 0·0019). For total hip score, the difference was close to borderline significance (P = 0·0698). Median Ca intake from dairy products was lower in the group of women with previous fractures than in those without fracture history (336 v. 395 mg/d; P = 0·0254). The main dairy source of Ca in the analysed group included milk drinks, rennet cheese and milk. CONCLUSIONS: Higher dairy Ca intake is recommended, since a number of the women analysed were unable to satisfy their Ca requirement exclusively from their diet.

Effects of the DL76 Antagonist/Inverse Agonist of Histamine H3 Receptors on Experimental Periodontitis in Rats: Morphological Studies.

BACKGROUND: Periodontitis preceded by gingivitis is the most common form of periodontal disease and occurs due to the interaction of microorganisms present in the complex bacterial aggregates of dental plaque biofilm and their metabolism products with periodontal tissues. Histamine is a heterocyclic biogenic amine acting via four types of receptors. Histamine H3 receptors act as presynaptic auto/heteroreceptors to regulate the release of histamine and other neurotransmitters. AIM: Since the nervous system is able to regulate the progression of the inflammatory process and bone metabolism, the aim of this study was to investigate the effects of DL76, which acts as an antagonist/inverse agonist of H3 receptors, on the course of experimental periodontitis. MATERIALS AND METHODS: This study was conducted in 24 mature male Wistar rats weighing 245-360 g, aged 6-8 weeks. A silk ligature was placed on the second maxillary molar of the right maxilla under general anesthesia. From the day of ligating, DL76 and 0.9% NaCl solutions were administered subcutaneously for 28 days in the experimental and control groups, respectively. After the experiment, histopathological, immunohistochemical and radiological examinations were performed. RESULTS: Ligation led to the development of the inflammatory process with lymphocytic infiltration, increased epithelial RANKL and OPG expression as well as bone resorption. DL76 evoked a reduction in (1) lymphocytic infiltration, (2) RANKL and OPG expression as well as (3) bone resorption since the medians of the mesial and distal interdental spaces in the molars with induced periodontitis were 3.56-fold and 10-fold lower compared to the corresponding values in saline-treated animals with periodontitis. CONCLUSION: DL76 is able to inhibit the progression of experimental periodontitis in rats, as demonstrated by a reduction in the inflammatory cell infiltration, a decrease in the RANKL/RANK OPG pathway expression and a reduction in the alveolar bone resorption.

Height loss in postmenopausal women predicts multiple fractures in 10-year follow-up: results from the RAC-OST-POL study.

INTRODUCTION: In daily practice the diagnostic process for osteoporosis in elderly patients should also include physical assessment. The aim of the study was to verify the hypothesis that height loss (HL) predicts fracture incidence. MATERIAL AND METHODS: The study was performed in an epidemiological sample of postmenopausal women recruited in the RAC-OST-POL study. At baseline, data were collected in 978 postmenopausal women at a mean age of 66.48±7.6 years, and at 10-year follow-up 640 patients remained, with a mean age of 75.04 ± 6.95 years. Current height and HL were established in regard to maximal life height. Data on fracture incidence were gathered throughout the period of observation. RESULTS: During the follow-up period 190 osteoporotic fractures were noted. Ninety-one women had one fracture, and in 38 women, multiple fractures occurred. In the fractured and unfractured subgroups, HL was 5.45 ± 3.28 and 4.8 ± 3.56 cm, respectively, and differed significantly (p < 0.05). HL in subjects without fracture did not differ from those with one fracture (HL 4.8 ± 3.56 vs. 4.8 ± 2.66 cm, respectively). For patients with more than one fracture HL was 7.03 ± 4.06 cm and was significantly higher than in subjects with one or without any fracture (p < 0.01). Based on receiver operating characteristic (ROC) analysis, HL of 6 cm was identified as the cut-off point for high risk of multiple fractures. CONCLUSION: HL of at least 6 cm is the predictor of multiple fractures in a prospective observation of a representative epidemiological female sample. Therefore, the measurement of HL should always be included in patients' assessments.

Fracture risk and fracture prevalence in women from outpatient osteoporosis clinic and subjects from population-based sample: A comparison between GO Study and RAC-OST-POL cohorts.

BACKGROUND: The method of recruiting the study subjects is an important element of the study design. It can have a strong influence on the results. Different recruitment schedules can give a different picture of the studied phenomenon. OBJECTIVES: The aim of the study was to compare bone health in a group of female patients treated for osteoporosis with a population-based sample. MATERIAL AND METHODS: A cohort of women from GO Study from 1 outpatient osteoporotic clinic (n = 1442, mean age 65.8 ±6.7 years) and population-based female sample of RAC-OST-POL Study (n = 963, mean age 65.8 ±7.5 years) were studied. Mean age did not differ between groups. Mean weight, height and body mass index (BMI) in subjects from GO Study and RAC-OST-POL Study were 69.5 ±13.1 kg, 157.8 ±6.1 cm and 27.9 ±5.1 kg/m2, and 74.2 ±13.7 kg, 156.0 ±6.0 cm and 30.5 ±5.4 kg/m2, respectively, and differed significantly (p < 0.0001 for each variable). Data on clinical risk factors for osteoporosis and fractures were collected. Bone densitometry at hip was performed using a Prodigy or Lunar DPX device (GE Healthcare, Waukesha, USA). Fracture risk was established using FRAX, Garvan and POL-RISK. RESULTS: Mean values of T-score for femoral neck in subjects from GO Study and RAC-OST-POL Study were -1.67 ±0.91 and -1.27 ±0.91 and differed significantly (p < 0.0001). In GO Study and RAC-OST-POL Study, there were 518 (35.9%) and 280 (29.1%) subjects with fractures, respectively. The fracture frequency was significantly higher in the GO Study group (p < 0.001). Among clinical risk factors, only rheumatoid arthritis (p < 0.0001) secondary osteoporosis (p < 0.0001) and falls (p < 0.0001) were more frequent in RAC-OST-POL Study. Fracture risk established using FRAX, Garvan and POL-RISK calculators was significantly greater in patients enrolled in the GO Study than in subjects from the RAC-OST-POL population-based sample (p < 0.0001 for each variable). CONCLUSIONS: Differences noted between female patients treated for osteoporosis and population-based sample, especially in regard to fracture risk, reveal a strong influence of recruitment criteria on study results in the field of bone health and osteoporosis.

Functional status as a predictor of the incidence of falls in 10-year follow-up: results from the RAC-OST-POL study.

INTRODUCTION: The aim of this prospective study was to establish the influence of baseline functional status on the incidence of falls. MATERIAL AND METHODS: The study was performed in an epidemiological sample of postmenopausal women from the RAC-OST-POL study. At baseline there were 978 postmenopausal women with a mean age of 65.9 ± 7.6 years, and at the end of 10-year follow-up 640 patients with a mean age of 65.04 ± 6.95 years remained in observation. Functional status was established at baseline using a stand up and go test (SAG) and the Lawton Instrumental Activities of Daily Living (IADL) scale. Afterwards, data on fall incidence were updated annually using phone interviews. RESULTS: In a 10-year period of observation, in 384 (60%) women at least one fall occurred. At baseline, 90% of subjects achieved maximal value in the IADL scale (24 points). Although the difference between mean IADL score in those who fell and did not fall was noticeable (23.50 ± 1.68 vs. 23.65 ± 1.47, respectively), the category of any IADL score below 24 points was significantly more frequent in women with falls (71.9% vs. 28.1%; chi-square 4.2, p < 0.05). The SAG score in the subgroup with falls was (10.75 ± 3.39) and did not differ in comparison to subgroup without falls (10.27 ± 2.72). CONCLUSION: The baseline result of the IADL scale but not that of the SAG test are related to the incidence of falls in a 10-year prospective observation. Adequate correction of functional status may benefit patients and reduce the fall rate.

Prognostic relevance of clinicopathological factors in sporadic and syndromic odontogenic keratocysts: A comparative study.

BACKGROUND: Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a higher tendency to relapse. The prognostic efficacy of various markers in sporadic and syndromic OKCs is unclear, and so are the results of studies on the usefulness of immunohistochemistry in distinguishing syndromic from sporadic OKCs. OBJECTIVES: This retrospective study aimed to compare the prognostic relevance of various clinicoradiological and histopathological features, as well as the immunoexpression of COX-2, Bcl-2, proliferating cell nuclear antigen (PCNA), p53, Ki-67, osteoprotegerin (OPG), receptor activator of nuclear factor κ B (RANK) and receptor activator of nuclear factor κ B ligand (RANKL), as well as RANKL/OPG balance between sporadic and syndromic OKCs, and to test their utility in distinguishing the 2 types of OKC. MATERIAL AND METHODS: We compared the immunoexpression of the aforementioned markers between 31 sporadic and 12 syndromic OKCs, and tested clinicopathological findings and levels of immunostaining against recurrence. RESULTS: We found a significant association between NBCCS and OKC recurrence. There were significant differences in PCNA, p53 and OPG immunoexpression between sporadic and syndromic OKCs. We also found that recurrent sporadic OKCs were significantly larger and markedly more often associated with cortical perforation. Recurrent sporadic OKCs exhibited COX-2 upregulation, but we failed to demonstrate its prognostic relevance. Recurrent syndromic OKCs showed a markedly higher RANKL > OPG ratio. CONCLUSIONS: The NBCCS-associated OKCs are significantly more prone to recur than their sporadic counterparts. Larger size and radiological signs of cortical perforation in sporadic OKCs may indicate a higher risk of recurrence. The COX-2 is upregulated in recurrent sporadic OKCs, whereas recurrent syndromic OKCs exhibit higher RANKL and lower OPG expression; however, these findings have no prognostic relevance. The immunoexpression of p53, PCNA and OPG may help to distinguish syndromic from sporadic OKCs.

Does the Immunohistochemical Expression of CD44, MMP-2, and MMP-9 in Association with the Histopathological Subtype of Renal Cell Carcinoma Affect the Survival of Patients with Renal Cancer?

CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of patients with renal cancer. The study population included 243 clear cell RCC (ccRCC) and 59 non-ccRCC cases. A total of 302 tumors were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The expression levels of the proteins were scored by semi-quantitative methods, and the correlation with overall patient survival was verified. We found no significant differences in CD44 expression levels between cc-RCC and non-ccRCC cases; however, significant differences existed in the degree of MMP-2 and MMP-9 expression between cc-RCC and non-ccRCC cases. There was significantly higher MMP expression in non-ccRCC than in ccRCC cases. Univariate Cox regression analysis showed that increased CD44 expression and histopathological subtype of ccRCC were predictors of shorter overall survival. Moreover, MMP-2 overexpression slightly reduced the risk of patient death, while MMP-9 expression did not show an association with patients' survival. However, on multivariate analysis, only the histopathological subtypes of ccRCC and CD44 expression were independent risk factors for patient death.

Does the VHL polymorphisms rs779805 and rs1642742 affect renal cell carcinoma susceptibility, prognosis and survival in Central European population?

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. The von Hippel-Lindau (VHL) tumor suppressor gene play an essential role in the tumorigenic pathway of clear cell RCC (ccRCC). This study was aimed to clarify the influence of VHL polymorphisms on ccRCC susceptibility and survival in Central European population. We genotyped 2 single-nucleotide polymorphisms (SNPs) rs779805 and rs1642742 in VHL gene and assessed their associations with ccRCC risk, clinicopathologic parameters, and prognosis in 171 cases. The selected SNPs were genotyped by ROCHE LifeCycler 96 using tumor tissue-derived DNA. Both SNPs do not directly influence ccRCC susceptibility and overall survival. A significant associations were found between allele G and genotypes AG and GG of rs779805 in the VHL tumor suppressor gene and increased tumor size, as well as high nuclear grade. Furthermore, a statistically significant association was observed between rs1642742 of VHL gene and low pathological tumor stage and between rs779805 of VHL gene and high pathological tumor stage. Both investigated SNPs can be important prognostic indicators of RCC in the Central European population, because statistically significant associations were observed between evaluated VHL polymorphisms and the best known factors with proven prognostic significance in kidney cancer.

Height Loss Is an Independent Predictor of Fracture Incidence in Postmenopausal Women: The Results from the Gliwice Osteoporosis Study (GO Study).

BACKGROUND: The aim of a longitudinal, retrospective study was to establish variables predicting fracture incidence over a decade. METHODS: The study sample comprises a group of 457 postmenopausal women aged over 55 years, recruited from the database of an outpatient osteoporotic clinic. Several variables with potential influence on bone status, including the measurement of body height and hip bone densitometry, were collected. BMD at the femoral neck (FN BMD) was established using a Prodigy device (Lunar, GE, USA). Current body height was compared with the maximal historical body height in early adulthood, as reported by the patient. RESULTS: Three hundred and ninety-four women did not have fractures during the follow up, and 63 subjects presented fractures. Subjects with fracture had lower FN BMD with a T-score of -1.86 ± 1.04 compared to -1.44 ± 0.89 in those without fractures (p < 0.001). Mean height loss (HL) was 3.47 ± 2.11 cm in fractured subjects and 2.50 ± 2.47 cm in unfractured ones, and differed significantly, p < 0.01. Fracture incidence was significantly related to age, rheumatoid arthritis, falls, and previous fractures. In the multivariable analysis using logistic regression, FN BMD, baseline fracture, and HL were identified as the significant predictors of fractures of follow up. CONCLUSIONS: Osteoporotic fractures in postmenopausal women were predicted by FN BMD, prior fracture(s), and HL easily established during physical examination.

POL-RISK: an algorithm for 10-year fracture risk prediction in postmenopausal women from the RAC-OST-POL study.

INTRODUCTION: Fragility fractures are the major consequence of osteoporosis. Thus, fracture risk assessment is an essential part of the diagnostic process in osteoporosis. OBJECTIVES: The aim of the study was to develop an algorithm for fracture risk prediction. PATIENTS AND METHODS: Bone status was evaluated in a population­basedcohort of postmenopausal women at a mean (SD) age of 66.4 (7.8) years. Subsequently, all participants were contacted by phone once a year (for 10 consecutive years) to update their history of fractures. At the end of the 10­year follow­up, the number of the study participants was 640, of whom 129 had a history of 190 osteoporotic fractures recorded during the study period. Statistical analysis included multistep data preprocessing, feature selection, identification of fracture risk factors, and design of the final model. Logistic regression models were fitted and used for the evaluation of variables from determined feature sets, including global fit measures, as well as individual parameters, such as the Wald statistic and P value, odds ratio, and 95% CI. RESULTS: The 10­year risk for any fracture depended on the age of the patient, the number of recorded fractures after the age of 40 years, femoral neck bone mass, and the occurrence of falls during the previous year. The achieved equation was incorporated into an algorithm, available at the www.fracture­risk.pl webpage. CONCLUSION: A fracture prediction algorithm was developed in a longitudinal study to enable calculation of the 10­year fracture risk. Identification of patients at a high risk of fracture should be followed by implementation of appropriate treatment strategy to reduce the number of future fractures.