[Bone loss in women with malignant genital neoplasms]. / Utrata masy kostnej u pacjentek z notwtworami zlosliwymi narzadów plciowych.

Nowadays, women with genital cancers live longer due to early diagnosis and better treatment schemes. Only few studies assessed bone mass in patients with genital cancer Osteoporosis is a condition characterized by progressive loss of bone mass, weakening of the spatial structure of the bone, and increased susceptibility to fractures. Osteopenia is a condition of reduced, but not yet reaching the pathological values, bone density in relation to norms for age and sex. Metastases are the primary cause of death in cancer patients. It is estimated that approximately half of people dying due to cancer have bone metastases. Osteoporosis in neoplastic disease may occur due to bone metastases or therapy-related adverse effects, i.e. reduced bone mineral density (BMD). Bone microenvironment provides a good medium for the growth of cancer cells. BMD of the femur and spine should be measured by DXA. Computed tomography (CT) and magnetic resonance imaging (MRI) are the techniques used to detect bone metastases. Lifestyle is the key to improving the quality of life and maximize any pharmacological treatment in cancer patients. It is proposed that treatment of cancer without bone metastases does not require therapy increasing bone mass. Further studies in women treated for gynecological malignancies undergoing oophorectomy and adjuvant treatment are needed to elucidate the mechanisms associated with bone loss.

Association of common WRAP 53 variant with ovarian cancer risk in the Polish population.

Among many alterations within the TP53 gene the rs1042522 (C72G, p.Pro72Arg) has been associated with numerous cancers , however the results differ between populations for opposite Pro or Arg alleles. Similar thus inconclusive results are observed in ovarian cancer, which may suggest that the rs1042522 does not influence ovarian carcinogenesis directly, but might be linked to another pathogenic alteration. WRAP53 which overlaps the TP53 is required to maintain normal levels of p53 upon DNA damage, but also when altered may independently increase the risk of cancer. To evaluate the association between three SNPs located in WRAP53-TP53 region: rs1042522, rs2287497, rs2287498 and ovarian cancer risk in Polish population we genotyped 626 cases and 1,045 healthy controls. Our results provide the evidence for an association between studied SNPs and a risk of invasive ovarian cancer in Poland. We found that CC homozygotes in rs1042522 were more frequent in cancers when compared to controls (OR = 1.46, p = 0.03). Similarly in WRAP53 both TT homozygotes in rs2287497 (OR = 1.95, p = 0.03) and AA homozygotes in rs2287498 (OR = 2.65, p = 0,01) were more frequent among cases than healthy individuals. There is also a suggestive evidence that specific homozygosity of studied SNPs in TP53-WRAP53 region is significantly overrepresented in ovarian cancer patients. In conclusion SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53.

[Circulating tumor cells (CTCs)--clinical significance in patients with ovarian cancer]. / Krazace komórki nowotworowe--znaczenie kliniczne u chorych na raka jajnika.

Circulating tumor cells (CTCs) are cells released from the primary tumor and circulating in peripheral blood. CTCs are an important element in the process of understanding the biology of metastases. In the future CTCs may be used as biomarkers for the assessment of neoplastic process progression and recurrence. The CTCs presence in peripheral blood was described in various tumors, and the possibility of their use in clinical procedures was demonstrated. The appearance of CTCs is a sign of metastasis formation and its spread via the circulatory system. Ovarian cancer is a special type of tumor as it grows and recurs mainly in the abdominal cavity. Despite advances in therapeutic methods, more than half of the patients with ovarian cancer experience disease recurrence which cannot be cured. Therefore, it is important to seek better treatment strategies for patients with advanced disease. There is evidence that CTCs in patients with ovarian cancer may be associated with the appearance of recurrences, disease-free time and total survival time. Detection and molecular analysis of CTCs may also be a non-invasive test for detecting an early stage of the disease, impossible to diagnose using currently available diagnostic tools. Monitoring can also be a prognostic factor enabling the evaluation of the therapeutic response. CTCs detection will contribute to better patient outcomes by using an improved system of diagnosis and monitoring of patient therapy allowing for immediate implementation or change of the treatment when necessary.

[No association between MTHFR 677C>T polymorphism and ovarian cancer risk in BRCA1 mutation carriers in Wielkopolska region]. / Polimorfizm MTHFR 677C>T nie wplywa na ryzyko rozwoju raka jajnika u nosicielek mutacji BRCA1 z Wielkopolski.

BACKGROUND: Increasing evidence indicates that genetic factors are involved in the process of carcinogenesis. BRCA 1 mutation has been proven to be responsible for increased risk of ovarian cancer However the importance of other genetic disorders, such as MTHFR polymorphism for increased risk of carcinogenesis, is still to be determined. Abnormal methylation seems to play a significant role in ovarian cancer pathogenesis. MTHFR catalyses the conversion of 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate which is a co-substrate in homocysteine remethylation into methionine. Thermolabile MTHFR protein variants with lower enzymatic activity are the effects of the mutation. AIM: The evaluation of 677C>T MTHFR polymorphism frequency in the group of ovarian cancer women with BRCA 1 mutation. The assessment of the MTHFR 677C>T polymorphism influence on ovarian cancer risk. METHODS: A group of 153 patients with ovarian cancer (Caucasian, Polish population in Wielkopolska region) were included into the study 3 mutations: 5382insC, C61G and 4153delA in BRCA1 gene, and genotype frequency within 677C>T MTHFR polymorphism, were identified. The analysis of genotype frequency was performed by means of PCR/RFLP method. RESULTS: 127 women without BRCA1 mutation and 26 with one of the mutations: 5382insC, C61G or 4153delA were qualified for the investigation. In the group with BRCA 1 mutation, 3 out of 26 patients were with TT genotype mutation of 677C>T polymorphism (12%). Heterozygotic genotype CT appeared in 13 cases out of 26 (50%), homozygotic CC in 10 out of 26 (38%). In the group of 127 ovarian cancer patients without BRCA1 mutation, TT genotype in 677C>T polymorphism was present in 5 women (4%). Heterozygotic genotype CT appeared in 61 cases (48%), similarly to homozygotic genotype CC-61 (48%). The highest value (OR = 3.18) was obtained when comparing the homozygotic TT genotype groups. None of the obtained values was statistically significant. CONCLUSION: Contrary to numerous suggestions in various publications, we did not confirm the correlation between MTHFR 677C>T polymorphism and the influence on the risk of ovarian cancer in BRCA1 mutation carriers in the investigated group of Polish women.

The 3020insC NOD2 gene mutation in patients with ovarian cancer.

OBJECTIVE: There is an increasing evidence that genetic factors play a role in the etiology of malignant tumors. Mutations of BRCA1 and BRCA2 genes are responsible for an increased risk of ovarian cancer. The role of mutations in NOD2 gene in this type of neoplasm is still under investigation. THE AIM: The aim of this study was to determine: 1. incidence of NOD 2 3020insC constitutional mutation in a group of consecutive women with ovarian cancer, 2. risk of developing ovarian cancer in patients with NOD2 gene mutation, 3. clinical and pathological features of ovarian cancer in NOD2 gene mutation carriers. PATIENTS AND METHODS: Clinical and pathological data were collected from 257 non-selected patients with primary epithelial ovarian cancer. The researches identified NOD2 3020insC gene mutation. On the basis of patient source documentation we obtained the data concerning the age of patients at diagnosis, histopathological recognition, FIGO stage and morphological grade G. RESULTS: 19 out of 257 women were identified with germ-line 3020insC mutation of NOD2 gene (7.39%). An increased risk of ovarian cancer in NOD2 mutation carriers was not revealed (OR=1.01; p=0.928; 95% Cl=0.61-1.66). The mean age at diagnosis of patients with NOD2 mutation was 54.8 (SD=9.9), while for non-carriers it was 53.2 (SD=10.2). The difference between these frequencies was statistically irrelevant (p=0.550). Clinical and pathological profile of ovarian cancer was made. We assessed the following features: age at disease onset, histopathology, FIGO stage and morphological grade G. For NOD2 mutation carriers no statistically significant features of ovarian cancer were revealed. CONCLUSION: 1. Despite high frequency of constitutional mutations occurrence in NOD2 gene in women with ovarian cancer, genetic testing seem not to be justified in all women diagnosed with this disease. 2. Due to a lack of increased risk of ovarian cancer in NOD2 gene mutation carriers, proceedings for them may not differ from recommendations for general population. 3. It is difficult to determine characteristic clinical and pathological features of ovarian cancer for NOD2 gene mutation carriers.

Analysis of hMLH1 and hMSH2 expression in cisplatin-treated ovarian cancer patients.

BACKGROUND: Loss of DNA mismatch repair may result in resistance to platinum- based anticancer drugs. The hMLH1 and hMSH2 proteins play a critical role in the maintenance of genome integrity and are involved in resistance to platinum-based therapy in colorectal cancer, which is deficient in hMLH1 protein and endometrial cancer, as well as in hMSH2 protein. However, the predictive value of MLH1 and MSH2 expression in ovarian cancer cisplatin-resistance is still to be determined. OBJECTIVE: The aim of this study was to investigate the expression of hMLH1 and hMSH2 proteins in ovarian carcinoma specimens and to evaluate their prognostic significance by means of overall survival (OS) and progression-free survival rates (PSF). MATERIAL: Ovarian cancer tissues were obtained from 61 patients: 45 platinum-sensitive and 16 platinum-resistant. hMLH1 and hMSH2 proteins expression was evaluated by immunohistochemistry, with the use of mouse monoclonal antibodies clone 14 for hMLH1 and clone FE11 for hMSH2. The log-rank test and Kaplan-Meier statistics were used to analyze the relationship between proteins expression and progression free survival, as well as the overall survival. RESULT: No significant correlation was found between hMLH1 and hMSH2 expression and overall survival and progression free survival in the group of patients sensitive and resistant to cisplatin. No significant difference was found in proteins expression intensity between the two compared groups of patients. Age of patients, type of cancer histology, FIGO staging, grading, clinical response and CA 125 did not reveal correlation with the expression of the analyzed proteins. CONCLUSION: The immunohistochemical expression of hMLH1 and hMSH2 proteins in ovarian cancer has no predictive value in resistance to cisplatin.

Retrospective analysis of the non-surgical treatment of developmental dysplasia of the hip using Pavlik harness and Frejka pillow: comparison of both methods.

Background. Several different orthoses are used for the treatment of developmental dysplasia of the hip (DDH). The most popular are the Frejka pillow, the Pavlik harness, the von Rosen splint, and the Koszla splint. The purpose of our study was a retrospective comparative analysis of the non-surgical treatment of DDH using Pavlik harness and Frejka pillow. Material and methods. We studied 238 children (438 hips), 213 girls and 25 boys. In this group 143 children were treated using the Frejka pillow and 95 using the Pavlik harness. The development of the infants' hips was assessed by ultrasonography. Results. 89% of the hips treated with Frejka pillow and 95% treated with Pavlik harness were successfully reduced. In children with dysplastic hips diagnosed before age 24 weeks, the Pavlik harness is effective. In childrern diagnosed after 24 weeks of life the Frejka pillow is more effective. In spite of appropriate treatment using both methods, avascular necrosis was found in 12% of the hips treated with Frejka pillow and 7% in the Pavlik group. Conclusions. Pavlik-stabilized hips in human position to promote concentric reduction shorten the duration of treatment, allow the mother to clean the infant easily and decrease the risk of avascular necrosis. The position achieved by using the Frejka pillow is not as appropriate, but the results are better than with the Pavlik harness in children diagnosed after 6 months of age.