Utility of PET/CT in the diagnosis of recurrent ovarian cancer depending on CA 125 serum level.

UNLABELLED: The aim of this study was to estimate the diagnostic value of common application of CA 125 level measurement and 18F-FDG PET/CT examination in patients with a suspicion of recurrent ovarian cancer. PATIENTS, METHODS: A retrospective analysis was performed on a group of 68 patients aged 31-77 (average 57.7) with a suspicion of relapsing ovarian cancer who had CA 125 serum level measurement and PET/CT examination done with a maximum interval of 60 days. RESULTS: PET/CT examination result was positive in 33 patients (48.5%) and negative in 35 (51.5%). Level of CA 125 was significantly higher in women with a positive PET/CT result than in patients with a negative one (average 199.9 U/ml and 15.7 U/ml, respectively, p < 0.001). Nevertheless, comparison of CA 125 level in groups defined according to the localization of the relapse showed no significant differences. Moreover, the ROC analysis revealed that the optimal cut-off point of CA 125 concentration to predict positive PET/CT result was 17.6 U/ml. Area under the curve was 0.91. Sensitivity, specificity and accuracy in prognosticating positive PET/CT result for the selected cut-off point of 17.6 U/ml were 90.9%, 80.0% and 85.3%, respectively. CONCLUSION: CA 125 level does not depend on the localization of the recurrence. PET/CT is particularly useful in patients with a suspicion of relapsing ovarian cancer with CA 125 value of at least 17.6 U/ml.

Association of the IGF-I promoter P1 polymorphism with risk of cervical cancer.

Human papillomaviruses (HPV16, HPV18, HPV31, HPV33) are etiological agents in the development of cervical cancer. HPVs infect epithelial cells and depend on epithelial differentiation for the completion of their life cycle. Insulin-like growth factor I (IGF-I) is a potent mitogen involved in the regulation of cell proliferation and apoptosis of many cell types including normal and transformed epithelial cells. Deregulation of IGF-I expression and action is linked to diverse pathologies including cancer. A polymorphism in the P1 promoter region of the IGF-I gene may directly influence its expression. Using the PCR-SSCP method and sequencing of DNA, we identified a single nucleotide polymorphism (SNP) at -383(C>T) position of promoter P1 of the IGF-I in 16% of the study HPV-positive women with precancerous and cancerous lesions. In vitro, we observed that the SNP at-383(C>T) site significantly increased the reporter gene expresion in the HepG2 cell line, but not in the HeLa cell line relative to the wild type promoter. It suggests that the studied SNP can change expression of the IGF-I gene in distinct ways in different types of tissues. Deregulation of expression of the IGF-I gene can affect normal epithelium development and in case of HPV infection can potentially disrupt the virus life cycle and stimulate its passage into the oncogenic life cycle or persistent viral infections. Therefore, we propose that SNP C>T at the -383 position of P1 promoter may be one of the helpful prognostic markers in the diagnosis of cervical cancer development of women with persistent infection in the ectocervical epithelium. We have not found any association between the polymorphism CA repeats in the promoter P1 region of the IGF-I gene and suceptibility to HPV infection and cervical cancer development. The (CA)19 allele was the most common in the study of this group of women.

The prevalence of leptotrichia amnionii in cervical swabs of HPV positive and negative women.

UNLABELLED: The aim of the present study was to determine the prevalence of Leptotrichia amnionii in cervical swabs of women and its possible correlation with HPV infection and the stage of cervical cancer. MATERIAL AND METHODS: A total of 139 cervical swabs from healthy women with normal cytology, with dysplastic changes and with cervical cancer were tested for the presence of L.amnionii and high-risk HPV DNA by PCR methods. RESULTS: L. amnionii was found in normal vaginal flora and in women with bacterial vaginosis (BV), which suggests that it may be oportunistic pathogen. L. amnionii infection was diagnosed in 13.7% (19/139). Statistical analysis showed that there was positive association (p < 0.01) between the presence of L.amnionii in women with cervical cancer (38.5%) and its presence in women without cancer (11.1%). On the other hand, there was no statistically significant association between L.amnionii and HPV infections. CONCLUSION: The data presented in this study show for the first time the prevalence of L. amnionii infection in cervical specimens collected from 2004-2006 in Poznan and Lublin, Poland, and its association with HPV infection and the stage of carcinogenesis of the cervix.

Analysis of expression and structure of the TSG101 gene in cervical cancer cells.

Human papillomavirus (HPV)-mediated transformation of human epithelial cells has been recognized as a multi-step process in which additional unknown factors and (epi)genetic events are required. The tumor susceptibility gene 101 (TSG101) was discovered in mouse NIH3T3 fibroblast cells as a gene whose functional knockout leads to transformation. TSG101 protein is involved in a variety of important biological functions, such as ubiquitination, transcriptional regulation, endosomal trafficking, virus budding, proliferation and cell survival. It is suggested that TSG101 is an important factor for maintaining cellular homeostasis and that perturbation of TSG101 functions leads to cell transformation. Interestingly, a recent report showed up- or down-regulation of TSG101 in several human malignancies. At present, the role of TSG101 in cervical tumorigenesis is unexplained. TSG101 expression in tumors, where carcinogenesis is connected with viral infection, and a mechanism of TSG101 expression regulation in cancer cells are also unknown. The aim of our study was to estimate the TSG101 mRNA and protein level in cervical cancer and non-tumor epithelial cells. We also analyzed the TSG101 coding and promoter sequence using the PCR-SSCP technique and methylation pattern of the TSG101 promoter. Our real-time PCR and Western blot analysis showed decreased TSG101 mRNA and protein level in cervical cancer tissue in comparison to normal (non-tumor) HPV(-) and HPV16(+) epithelial cells. Our results suggest that TSG101 down-regulation in cervical cancer cells is not regulated by genetic or epigenetic events. However, we detected novel single nucleotide polymorphisms in the promoter of this gene.

The level of antibody against E6 HPV 16 oncoprotein in blood sera of women with chronic HPV 16 infection and cervical cancer.

UNLABELLED: The aim of this study was to estimate of the role of chronic HPV 16 infection and the presence of anti E6 HPV 16 in the initiation of the cancerogenesis process of cervical cancer. MATERIAL AND METHODS: The study included two groups of patients. The first group comprised 323 women observed for three consecutive years (1998-2000), in whom the presence of HPV 16 viruses was estimated by PCR, and the level of anti E6 HPV 16 antibodies was estimated in the plasma with ELISA. A similar test was performed in a group of 46 patients with cervical intraepithelial neoplasia (CIN), 91 patients with invasive cervical cancer and 22 women after hysterectomy and RTG-therapy. RESULTS: In 32 patients, chronic HPV 16 infection showed a steady rise in the mean absorbance level of anti E6 HPV 16 antibodies from 0.04 in 1998 to 0.06 in 2000, while in HPV-negative women the mean absorbance value was 0.03-0.04. Mean absorbance value in patients with CIN III and invasive cancer rose with advancing stage of the cancer process and lowered after completion of oncological treatment. The values were 0.14, 0.33 and 0.13, respectively. CONCLUSION: The persistence of chronic HPV 16 infection and accompanying steady rise in absorbance index caused by an increase in the level of antiviral antibodies are a clear warning signal preceding in time the histological process of cancerogenesis.

Detection of bone sialoprotein in human (pre)neoplastic lesions of the uterine cervix.

Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in the mineral compartment of developing bones. BSP is detected in a variety of human cancers, particularly those that metastasize to the skeleton. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. Since squamous cell carcinoma (SCCs) of the uterine cervix also frequently metastasizes to bone, we investigated whether BSP is expressed in human cervical cancer. We examined BSP expression in cervical tissue samples from 47 patients, including 19 normal tissues, 20 squamous intraepithelial lesions (SILs) (9 low and 11 high grade) and 8 invasive SCCs. BSP protein expression was evaluated by the immunophosphatase technique using a BSP polyclonal antibody in paraffin-embedded cervical biopsies. The abundance of BSP protein was significantly higher in invasive SCCs and high grade SILs than in normal cervix tissue samples and low grade SILs, which showed no or a low level of anti-BSP immunoreactivity. In situ hybridization experiments performed on representative cervix invasive SCCs frozen sections revealed that BSP transcripts were detectable in these lesions. Our study demonstrates that BSP expression is a common feature in high grade SILs and invasive SCCs of the uterine cervix. The prognostic value of BSP detection in these lesions and the potential role of BSP as an angiogenic factor in this type of cancer are currently under investigation.

Intratype HPV16 sequence variation within LCR of isolates from asymptomatic carriers and cervical cancers.

BACKGROUND: HPV16 is a predominant type of virus identified in genital lesions and strongly associated with the development of genital cancers. Infection with the virus is considered to be the main risk factor in the development of cervical cancer. Based on HPV16 DNA isolated from invasive cancers, a classification of intratype genetic variants was established and the strains were designated according to geographical regions. The HPV16 variants classification was based on isolates derived from cancers. OBJECTIVES: Analysis of HPV16 LCR variants isolated from asymptomatic carriers for comparison with cervical cancer isolates to examine whether a correlation can be found between cervical epithelium state and variant of HPV16 it carries. MATERIALS AND METHODS: The HPV16 LCR fragments were amplified by PCR using DNA isolated from cervical swabs and tissue sections then screened for nucleotide changes by SSCP. Polymorphic sites were analysed for regulatory protein binding properties by EMSA. RESULTS: Comparison of the two groups revealed that isolates from cervical cancers predominantly carry changes in sequences of YY1 binding sites (especially at nucleotide 7519), while variants from asymptomatic carriers contained nucleotide changes within or close to transcription binding sites for AP-1, Oct-1, NF1, Tef-1, Tef-2, Sp1, YY1 and viral E2. EMSA study showed that sequence changes in the segment alter binding and formation of transcriptional complexes in quantitative and/or qualitative manner and so they may inflict viral activity. CONCLUSION: The results of our study show that there might be HPV16 variants of decreased oncogenic potential therefore infection with such variants can recede.

[Ovarian cancer and endometriosis]. / Rak jajnika a endometrioza.

Endometriosis is a relatively common condition found in up to 29% of women undergoing laparotomies. The authors suggest that endometriosis could have undergone malignant change. They propose the criteria used to establish that a malignant tumor has develop in endometriosis: clear evidence of endometriosis should be found close to the tumor, the histopathological appearance should be such that origin of the tumor from endometriosis is plausible, no other primary site should be found. The authors consider that atypical endometriosis possesses a precancerous potential or is most frequently associated with endometrioid and clear cell carcinomas.

[Integrin alpha-6 in cervix neck squamous cell carcinoma HPV 16/18 positive and negative]. / Integryna alfa-6 w rakach plaskonablonkowych szyjki macicy HPV 16/18 pozytywnych i negatywnych.

In the present paper we study expression of alpha-6 integrin in normal paraepidermal epithelium, in CIN and in cervical invasive carcinoma HPV 16/18 positive and negative. The results suggest that alpha-6 integrin might be a marker for the evaluation of malignancy of squamous cell carcinoma. There is no correlation between the expression of alpha-6 integrin and the presence of HPV.

Relationship between HPV infection of the cervix and blood serum levels of steroid hormones among pre- and postmenopausal women.

Human papillomaviruses (HPVs) are frequently present in anogenital lesions but little is known about their role in carcinogenesis. There are steroid hormone response elements in virus genomes that influence expression patterns of viral genes. Activity of the elements may contribute to development of neoplasia in case of hormone level anomalies. Our study was to determine whether the presence of HPV DNA in cervical smears correlates with abnormal levels, of steroid hormones in blood serum. One hundred women aged 40-62 participated in the tests and were divided into two groups: premenopausal and postmenopausal (45 and 55 individuals, respectively). Presence of HPV DNA in cervical smears was detected by PCR and Southern blot hybridisation. Progesterone and estradiol levels in blood serum were measured by radioimmunoassay. Our study showed a higher prevalence of HPV DNA in women with higher levels of progesterone in blood serum. A relationship between hormone level and HPV DNA prevalence should alert clinicians about using hormone contraceptives and hormone replacement therapy.

[Immunohistochemical examination oncogenic c-erb-b2, egf-r proteins and antioncogenic p53 protein in vulvar cancers HPV-16 positive and negative]. / Immunohistochemiczne oznaczanie aktywnosci proliferacyjnej oraz bialek onkogennych C-ERB-B2, EGF-R i bialka antyonkogennego p53 w rakach sromu i stanach przedrakowych sromu i pochwy HPV 16 pozytywnych i negatywnych.

In vulvar cancers HPV 16 positive, HPV 16 negative, and vulvar and vaginal precancerous status (VIN, VAIN) immunohistochemical technik onko- and antioncogenic proteins were evaluated. The contrary correlation between HPV 16 presence and overexpression p53 were detected. It suggest the heterogenic etiology of these cancers. There was payed attention to high activity of virus replication and intensive virion production in VAIN. Nontreated vaginal lesion may make difficult to obtain a positive cervical HPV infection treatment.

[Biomarkers in primary ovarian cancers and after chemotherapy]. / Biomarkery w pierwotnych rakach jajnika i po leczeniu cytostatykami.

The authors analyzed the expression of oncogen and antioncogen proteins using immunoperoxidase technique with monoclonal antibodies in 49 primary ovarian carcinomas and 38 cancers after chemotherapy (second look) There was not found independent prognostic marker. But some results suggest, that in the individual cases estimate proliferative activity and overexpression P53 may give some information about intensitivity and quality of chemotherapy.

[Can the DNA-HPV study in vulvar squamous cell carcinoma have a diagnostic value?]. / Czy obecnosc DNA HPV w rakach sromu moze miec wartosc diagnostyczna?

The authors studied 27 vulvar cancer looking for relationship between presents of DNA HPV morphological structure and clinical follow-up. There is suggestion that HPV status may play a profitable role.

[Non-neoplastic epithelial disorders associated with vulvar carcinoma]. / Nablonkowe, nienowotworowe choroby wspólistniejace z rakiem sromu.

The purpose of this paper has been clinical problems associating squamous cell carcinoma of the vulva co-existing with non-neoplastic epithelial disorders. We analyzed 46 women with vulvar carcinoma. Non-neoplastic epithelial disorders we found in 17% cases. In conclusions we suggest the follow-up in patient with non-neoplastic epithelial disorders must be held the same like with vulvar carcinoma.

[Primary melanoma of the uterine cervix in a 19 year old woman--case report]. / Pierwotny czerniak szyjki macicy u 19 letniej kobiety--opis przypadku.

UNLABELLED: Only 5% of all melanocytic malignancies in women originate in the genitalia, the most unusual of which is melanoma involving the uterine cervix. CASE: a 19 year old woman, presented with abnormal genital bleeding. In our hospital the clinical examination showed an exophytic bleeding tumor growing in the cervix uteri. A first vaginal biopsy showed a sarcoma colli uteri. A new biopsy confirmed the clinical diagnosis of malignant melanoma. Subsequently a Wertheim-Meigs hysterectomy with bilateral adnexectomy and removal of upper half of the vagina and regional lymphadenectomy was performed. Next the patient received several courses of chemotherapy (DTIC).

[Markers of proliferation and morpho-immunologic parameters in evaluation of prognostic factors in endometrial tumors]. / Markery proliferacji oraz parametry morfoimmunologiczne w ocenie czynników rokowniczych w rakach blony sluzowej macicy.

There were analysed prognostic factors in endometrial carcinomas. To essential prognostic factors were counted; proportion of cells in S-phase, DNA ploidy, proportion of Ki-67 positive cells and vascular invasion by cancer cells. All above-mentioned factors were not correlated to either the stage or the histopathologic subtype of the cancers. Application of proliferating markers may be useful for selecting a subgroup of patients for adjuvant therapy.

Lymphocyte subpopulations in the blood of women with HPV 16 positive and negative cervical cancer.

In this study the morphologic features and subpopulation of lymphocytes in the blood of women with uterine cervical cancer HPV 16 positive and HPV 16 negative was compared. The essential morphological differentiation in two groups of cancer was not found, but a statistically significant increase in CD 19 lymphocytes in the blood of women with cervical cancer HPV 16 positive was discovered. The authors suggest, that an increase in CD 19 might be connected with stronger expression of virus-oncogenic antigens on the neoplasma cells.

Human papillomavirus (HPV) in upper genital tract carcinomas of women.

Using nucleic acid hybridization and polymerase chain reaction (PCR) HPV-DNA sequence was detected in endometrial and ovarian carcinomas. This sequence was amplified with primer specific for E1 region of DNA-HPV 18 and hybridized with DNA-HPV 18. The presence of HPV-DNA in cancer studies suggests that human papillomavirus can also be involved in carcinogenesis of the upper genital tract of women.

New plant glycoprotein against methicillin resistant staphylococci and enterococci.

New glycoprotein (CML) isolated from Chelidonium maius exhibits good antibacterial activity against methicillin resistant staphylococci and enterococci. It may constitute new antimicrobial agent against methicillin and vancomycin-resistant staphylococci as well as multiresistant enterococci.