ABSTRACT
BACKGROUND/AIM: Despite well-organized Hungarian invitational mammography screening, participation rates have never reached 50%. This is similar to rates in Central Eastern Europe. In order to reduce breast cancer mortality, the participation rate should be at least 70%. This questionnaire-based study assessed the barriers associated with low adherence rates. MATERIALS AND METHODS: Women 45-65 years of age were interviewed by questionnaire containing 15 structured questions focused on socioeconomic status and barriers to screening. RESULTS: A total of 3,313 women completed the questionnaire. The main reasons for avoiding screening were work absenteeism (18.9%), fear of painful examination (18.39%), and poor understanding of mammography screening (14.94%). CONCLUSION: Education is required to increase awareness among women about the utility and availability of breast screening services. This report provides information on the appropriate level of intervention needed to increase screening participation in Hungary and other developing countries in Central Eastern Europe to reduce breast cancer-related mortality.
Subject(s)
Breast Neoplasms/diagnosis , Early Detection of Cancer , Mammography/statistics & numerical data , Mass Screening/statistics & numerical data , Aged , Breast Neoplasms/epidemiology , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Hungary/epidemiology , Incidence , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
INTRODUCTION: The European Society of Breast Cancer Specialists has created quality indicators for breast units to establish minimum standards and to ensure specialist multimodality care with the conscious aim of improving outcomes and decreasing breast cancer mortality. AIM: The aim of this study was to analyse the breast cancer care in the National Institute of Oncology according to the European Society of Breast Cancer Specialists requirements and in a large number of cases in order to present representative clinico-pathological data on the incidence of breast cancer in Hungary. METHOD: According to the European Society of Breast Cancer Specialists uniformed criteria clinico-pathological data of multimodality treated breast cancer cases were retrospectively analysed between June 1, 2011 and May 31, 2012. RESULTS: During the period of interest 906 patients underwent breast surgery for malignant or benign lesions. According to the European Society of Breast Cancer Specialists quality indicators the breast cancer care of the National Institute of Oncology is eligible. CONCLUSIONS: The diagnostic modalities and multimodality care of breast cancer of the National Institute of Oncology breast unit meets the critical mass and minimum standards of the European Society of Breast Cancer Specialists criteria. Orv. Hetil., 2016, 157(42), 1674-1682.
Subject(s)
Benchmarking/standards , Breast Neoplasms/therapy , Cancer Care Facilities/standards , Quality of Health Care/standards , European Union , Humans , Hungary , Retrospective Studies , Standard of CareABSTRACT
INTRODUCTION: The methods available for the diagnosis of thyroid nodules include physical examination, imaging, laboratory and fine-needle aspiration cytology tests. AIM: The aim of this study was to determine the quality assurance of fine-needle aspiration cytology of thyroid nodules. METHOD: Cytology results were rated to 6 categories according to the Bethesda System for Reporting Thyroid Cytopathology (2008) (I. nondiagnostic; II. benign; III. atypia of undetermined significance; IV. follicular neoplasia; V. suspicious for malignancy; VI. malignant). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 1384 patient with thyroid nodule underwent fine-needle aspiration biopsy cytology. Smears were classified I. inadequate in 214 (15.9%); II. benign 986; III. atypical 56; IV. follicular neoplasm 41; V. suspicious for malignancy 18; VI. malignant 33 cases. Two hundred and twenty seven (16.8%) of the cases were operated and histologically verified. The positive predictive value in the benign category was 98.25% and in the malignant 88.46%. The sensitivity of the follicular neoplasm was 66.67%. CONCLUSION: The results suggest that fine-needle aspiration cytology of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology has a high diagnostic accuracy. The auditing values of the results meet the proposed threshold values.
Subject(s)
Biopsy, Fine-Needle , Medical Records/standards , Point-of-Care Testing , Quality Assurance, Health Care , Thyroid Gland/pathology , Thyroid Nodule/diagnosis , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle/standards , Carcinoma/diagnosis , Female , Humans , Male , Middle Aged , Pathology, Clinical/standards , Point-of-Care Testing/standards , Predictive Value of Tests , Sensitivity and Specificity , Thyroid Neoplasms/diagnosis , Thyroid Nodule/pathologyABSTRACT
INTRODUCTION: Liquid-based cervical cytology has been developed as an alternative for conventional Papanicolaou cervical cytology. AIM: The aim of this study was to determine the quality assurance of liquid-based cervical cytology. METHOD: 4573 cervical cytology smears were classified according to the Bethesda (2001) system. Human papilloma virus infection was detected and subtyped from reflex test using real-time polymerase chain reaction. RESULTS: 4573 smears were classified according to the Bethesda (2001) system. Negative diagnosis was made in 2323 cases (50.8%), non neoplastic in 2017 cases (44.1%), and positive for intraepithelial lesions or malignancy in 233 cases (5.1%). Unsatisfactory smear for diagnosis was found in 43 cases (0.9%), low-grade squamous intraepithelial lesion in 87 cases (1.9%), high-grade squamous intraepithelial lesion in 24 cases (0.5%), and carcinoma in 23 cases (0.5%). Fifty-nine of the cases were histologically verified and 4 falsely negative cases were detected. The sensitivity, specificity and the positive predictive value were 93.2%, 100% and 100%, respectively. Compared to an identical time periods of the previous three years, the low- and high-grade squamous intraepithelial lesion increased from 0.82% to 2.51%. Eighty one human papilloma virus tests were performed with a positive predictive value of 99%. CONCLUSIONS: The auditing values of the liquid-bases cervical cytology results meet the proposed threshold values. Liquid-bases cervical cytology is an alternative cervical cytology and it seems to be significantly better than conventional Papanicolaou cervical cytology in all parameters.
Subject(s)
Cervix Uteri/pathology , Cervix Uteri/virology , Early Detection of Cancer/methods , Mass Screening/methods , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Vaginal Smears/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cytopathogenic Effect, Viral , Female , Humans , Hungary , Middle Aged , Papillomaviridae/genetics , Predictive Value of Tests , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virologyABSTRACT
INTRODUCTION: The methods available for the diagnosis of lung cancer include radiologic, cytologic and pathologic procedures. AIMS: The aim of this study was to determine the quality assurance of CT guided fine needle aspiration cytology of lung nodules. METHODS: Cytology results were rated to 4 categories (positive; suspicious; negative; not representative). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 128 patients underwent CT-guided percutaneous fine-needle aspiration biopsy cytology (63 males; 65 females; mean age 62.8 years). Smears were adequate in 99 cases and inadequate in 29 cases. The average diameter of the nodules was 3.28 cm. Thirty three (25.6%) of the cases were histologically verified and 2 falsely negative and 2 falsely positive cases were detected. The sensitivity and the positive predictive value were 88.8% and 88.8%, respectively. Pneumothorax developed in 7 (5.4%) cases. CONCLUSION: These results suggest that CT-guided transthoracic fine needle aspiration cytology has a high diagnostic accuracy and an acceptable complication rate. The auditing valves of the results meet the proposed threshold values.
Subject(s)
Biopsy, Fine-Needle/methods , Image-Guided Biopsy/methods , Quality Assurance, Health Care , Solitary Pulmonary Nodule/diagnostic imaging , Solitary Pulmonary Nodule/pathology , Tomography, X-Ray Computed , Aged , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Middle AgedABSTRACT
The authors present the diverse etiology of nipple discharge, which background may be a tumor. They discuss the checkup ways of nipple discharge and review in detail the galactographic technique and evaluation. The examination of pathologic nipple discharge is essentially based on contact cytology, x-ray-, and ultrasound mammography. Consequently, galactography is applied by filling the ducts with contrast material. The final diagnosis is rendered by histologic examination, following the operation. The authors demonstrate the application and role of galactography through various cases.
Subject(s)
Breast Diseases/diagnosis , Exudates and Transudates , Nipples , Adult , Aged , Breast Diseases/diagnostic imaging , Breast Diseases/pathology , Breast Diseases/surgery , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Lobular/diagnosis , Contrast Media , Diagnosis, Differential , Female , Fibrocystic Breast Disease/diagnosis , Humans , Mammography , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Nipples/pathology , Nipples/physiopathology , Ultrasonography, MammaryABSTRACT
UNLABELLED: The National Public Health Program has established the organized mammography screening in Hungary. The aim of this study was to conduct an audit of "gray zone" smears of the organized mammography screening in comparison with histopathological diagnoses. METHODS: Cytology results were rated to C3 atypia probably benign and C4 suspicious of malignancy. RESULTS: 1361 women had aspiration cytology performed from a total of 47,718 mammography non-negative lesions. 105 (7.8%) were diagnosed as C3, whereas 78 (5.7) as C4. Of the 105 patients with C3 diagnosis 61 (58%) patients underwent surgical biopsy. Histology proved malignancy in 20 (32.8%) cases, and benign lesion in 41 (67.2%) cases. All (100%) of the 78 patients with C4 diagnosis had open biopsies; 69 (88.4%) cases were histologically malignant and 9 (11.6%) cases were benign lesions. CONCLUSION: The auditing results of fine needle aspiration cytology of "gray zone" in organized mammography screening meet the proposed threshold values. Authors conclude that the "gray zone" category in breast cytology is useful and of value if used judiciously.
Subject(s)
Biopsy, Fine-Needle , Breast Diseases/diagnostic imaging , Breast Diseases/pathology , Breast/pathology , Mammography , Mass Screening/methods , Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Female , Fibroadenoma/diagnostic imaging , Fibroadenoma/pathology , Fibrocystic Breast Disease/diagnostic imaging , Fibrocystic Breast Disease/pathology , Fibrosis/diagnostic imaging , Humans , Middle Aged , Sensitivity and SpecificityABSTRACT
UNLABELLED: The National Public Health Program has established the organized mammography screening in Hungary. AIM: The aim of our study was to determine the quality assurance of breast aspiration cytology. METHOD: Cytology results were rated to 5 categories (C1, C2, C3, C4 and C5). All cytology reports were compared with the final histology diagnosis. RESULTS: 1361 women had aspiration cytology diagnosis performed from a total of 47718 mammography non-negative lesions. There were 805 (59.1%) benign and 187 (13.7%) malignant alterations. Sensitivity was 91%, specificity 88%, positive predictive value 96.6% and negative predictive value turned to be 71% (p<0.001). CONCLUSION: The auditing values of fine needle aspiration cytology in our laboratory meet, or in certain aspects exceed the proposed minimum threshold values.
Subject(s)
Biopsy, Fine-Needle/standards , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/prevention & control , Mammography/standards , Quality Assurance, Health Care , Early Detection of Cancer , Female , Humans , Hungary , Middle Aged , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
The molecular basis for the exquisite sensitivity of testicular germ cell tumours of adolescents and adults (TGCTs), ie seminomas and non-seminomatous germ cell tumours, to chemo/radiotherapy has not been fully clarified so far. It has been suggested that it may be dependent on factors involved in the regulation of apoptosis. Seladin-1 is a multi-functional protein involved in various biological processes, including apoptosis. The aim of our study was to assess the expression of seladin-1 in different histological types of TGCTs, known to have varying treatment sensitivity, in order to establish whether this protein may influence cisplatin responsiveness in vitro. Seladin-1 expression levels, both at the mRNA and at the protein level, were higher in the adjacent normal parenchyma than in the pathological counterparts. In tumoural tissues, the level of expression differed among TGCT histological types. The highest tumour-expression level was found in teratoma, whereas the lowest was detected in seminoma, corresponding to the different chemo/and radiosensitivities of these tumour types. In common with other cancers, in TGCT-derived cell lines seladin-1 showed anti-apoptotic properties through inhibition of caspase-3 activation. We confirmed our results using a non-seminomatous cell line model (NT2) before and after differentiation with retinoic acid. Significantly higher seladin-1 expression was observed in the differentiated derivatives (teratoma) and an inverse relationship was found between seladin-1 expression and the amount of cleaved caspase-3. Seladin-1 silencing or overexpression in this cell line supports involvement of seladin-1 in cisplatin responsiveness. Seladin-1 silencing was associated with greater cisplatin responsiveness demonstrated by decreased cell viability and increased expression of apoptotic markers. In contrast, overexpression of seladin-1 was associated with a higher survival rate and a clear anti-apoptotic effect. In conclusion, we have demonstrated for the first time an important role for seladin-1 in the biology of TGCTs and provided new insights into cisplatin responsiveness of these tumours.
Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Neoplasms, Germ Cell and Embryonal/metabolism , Nerve Tissue Proteins/metabolism , Oxidoreductases Acting on CH-CH Group Donors/metabolism , Testicular Neoplasms/metabolism , Apoptosis/drug effects , Cell Differentiation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Gene Silencing , Humans , Male , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasms, Germ Cell and Embryonal/pathology , Nerve Tissue Proteins/genetics , Oxidoreductases Acting on CH-CH Group Donors/genetics , RNA, Neoplasm/genetics , RNA, Small Interfering/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Testicular Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
BACKGROUND: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ cell testicular tumors (GCT). Germ cells are particularly susceptible to apoptosis and it is reasonable to presume that GCTs are curable because of an intact and effective apoptotic pathway. PATIENTS AND METHODS: The expression of p53 and p21 was investigated in conjunction with the spontaneous apoptotic index in 20 refractory and 50 chemosensitive GCTs, with a complete follow-up. To detect a differentiation-dependent alteration in the apoptotic pathway, all of the histological tumor types were examined separately. RESULTS: Embryonal carcinoma components showed significantly higher p53 expression compared to other histological subtypes of GCTs. p21 was barely detectable in the majority of tumors. Seminomatous components showed no p21 expression. Mature teratomas and syncytiotrophoblasts showed significantly higher p21 expression than other tumor subtypes. Embryonal carcinomas showed significantly higher apoptotic indices than other non-seminomatous components. On the other hand, choriocarcinomas and mature teratomas showed the lowest spontaneous apoptotic potential. The apoptotic index correlated with the fraction of p53-positive cells, but not with the p21 expression rate. The refractory group showed significantly lower p53 expression, higher p21 expression and a higher apoptosis index than the sensitive group. CONCLUSION: Our results suggest that the p53 and p21 expression levels and the apoptosis index seem to be important factors in the issue of the chemosensitivity of GCTs. The protein expression pattern reflects a differentiation-dependent preference for G1/S-phase arrest in terminally differentiated syncytiotrophoblasts and mature teratoma cells, while p53 mediated apoptosis induction is meaning to less differentiated tumor types.
Subject(s)
Apoptosis/physiology , Cell Differentiation/physiology , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Adolescent , Adult , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Cyclin-Dependent Kinase Inhibitor p21/genetics , Drug Resistance, Neoplasm , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/metabolism , Testicular Neoplasms/genetics , Testicular Neoplasms/metabolism , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/geneticsABSTRACT
Retinoids as important growth and differentiation regulating agents have a potential role in the chemoprevention of head and neck squamous cell carcinoma (HNSCC). Despite the promising preclinical and early clinical findings, limitations of application are raised by intrinsic resistance acquired during carcinogenesis. Retinoic acid receptor beta2 (RAR beta2) is one of the proximate mediators of retinoid signalling and its expression is often diminished in early stages of head and neck carcinogenesis. One form of retinoid resistance has been associated with the methylation-induced silencing of the RAR beta gene. We studied primary HNSCC samples of different anatomical sites in respect of methylation, expression and allelic loss of RAR beta gene. A strong correlation (p<0.01) was found between hyper-methylation and reduced expression of RAR beta2, however the allelic loss at 3p24, the locus of RAR beta, did not considerably influence its mRNA level. Hypopharynx tumors showed significantly lower hypermethylation (p<0.05) and higher mRNA expression levels of RAR beta2 compared to the tumors located at other sites of the head and neck. We could also provide evidence that poorly differentiated grade 3 tumors had significantly higher RAR beta2 expression and lower methylation levels (p<0.05) than better differentiated grade 1 and grade 2 tumors. In addition, we found a good correlation between the methylation degree of the RAR beta2 promoter and the ages of patients. Collectively, our results suggest that evaluation of several factors such as tumor location, age, histology and methylation state of the RAR beta gene might contribute to the selection of patients for retinoid-based chemoprevention.
Subject(s)
Carcinoma, Squamous Cell/genetics , Gene Silencing , Head and Neck Neoplasms/genetics , Receptors, Retinoic Acid/genetics , Adult , Aged , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Differentiation , DNA Methylation , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Female , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Humans , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/metabolism , Laryngeal Neoplasms/pathology , Loss of Heterozygosity , Male , Middle Aged , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/metabolism , Oropharyngeal Neoplasms/pathology , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Receptors, Retinoic Acid/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
BACKGROUND: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ-cell testicular tumors (GCTs). The response to cisplatin-based chemotherapy has been related to Microsatellite Instability (MSI), which is caused by genetic or epigenetic changes in genes of the DNA Mismatch Repair (MMR) pathway. PATIENTS AND METHODS: We investigated 15 refractory and 36 chemosensitive GCTs for immunohistochemical loss of hMLH1, hMSH2 and hMSH6 protein expressions, in conjunction with hMLH1 gene methylation and MSI of GCTs, with a complete follow-up. RESULTS: A loss of either of the MMR protein expressions was detected in 14 cases (27.5%). Pathological hMLH1 protein expression was seen in 10 cases (19.6%). hMLH1 methylation was found in 11 cases (21.60%) and was highly correlated with loss of hMLH1 expression (p < 0.0001) and with immunohistochemically-detected MMR deficiency (p = 0.0005). MSI was found in 16 cases (31.4%). There was no correlation between hMLH1 methylation and MSI. Neither hMLH1 methylation status, nor MSI correlated with any of the clinicopathological parameters investigated (tumor stage, histology, resistance to systemic treatment). CONCLUSION: hMLH1 gene methylation was detected as a common alteration in GCTs, and correlated with the loss of hMLH1 protein expression (p < 0.0001). Neither hMLH1 gene methylation, MMR deficiency, nor MSI showed a relationship with the relevant clinicopathological parameters.
Subject(s)
Base Pair Mismatch , Carrier Proteins/genetics , DNA Repair/physiology , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/genetics , Nuclear Proteins/genetics , Testicular Neoplasms/drug therapy , Testicular Neoplasms/genetics , Adaptor Proteins, Signal Transducing , Adolescent , Adult , Antineoplastic Agents/pharmacology , Carrier Proteins/biosynthesis , Cisplatin/pharmacology , DNA Methylation , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Drug Resistance, Neoplasm , Humans , Male , Microsatellite Repeats/genetics , Middle Aged , MutL Protein Homolog 1 , MutS Homolog 2 Protein/biosynthesis , MutS Homolog 2 Protein/deficiency , MutS Homolog 2 Protein/genetics , Neoplasm Staging , Nuclear Proteins/biosynthesis , Nuclear Proteins/deficiencyABSTRACT
Fine needle aspiration cytology (FNAC) is an essential procedure in the diagnosis of premalignant and malignant lesions of the breast. A "gray zone" exists between benign and malignant lesions in FNAC of breast; there an unequivocal diagnosis cannot be reached. Lesions in "gray zone" are categorized as "probably benign with atypia" (C3) and "probably malignant" (C4). Authors compared the cytology with histopathology and clinical follow-up of "gray zone" breast lesions, classified either as C3 or as C4 by FNAC. Amongst the total of 1679 FNACs, 85 (5%) were diagnosed as C3, whereas 101 (6%) were diagnosed as C4. Of the C3 cases, 48 patients underwent surgical biopsy. Histology proved malignancy in 21 (44%) cases, and was benign in 27 (56%) cases. Eighty-five open biopsies were performed out of the C4 cases. The histology was malignant in 76 (89%) cases, and benign in 9 (11%) cases. Lesions belong to "gray zone" should be taken into consideration in the FNAC of the breast and patients must be informed regarding this fact.
Subject(s)
Biopsy, Fine-Needle , Breast Neoplasms/pathology , Breast Diseases/pathology , Diagnosis, Differential , Female , HumansABSTRACT
BACKGROUND: Amplification and/or overexpression of HER-2/neu are associated with poor clinical outcome in several epithelial tumors. However, the exact prognostic role of HER-2/neu expression in testicular germ-cell tumors is equivocal. PATIENTS AND METHODS: Since teratomas are relatively chemoresistant tumors, we evaluated the HER-2/neu alterations of 59 primary testicular teratomas and mixed germ-cell tumors containing teratomatous components using the standardized immunohistochemical method (IHC) (HercepTest) and Fluorescence in Situ Hybridization (FISH). RESULTS: HER-2/neu overexpression was detected in 14 (24%) out of 59 specimens. With IHC, teratomatous and choriocarcinoma components showed significantly higher HER-2/neu expression compared to other histological subtypes of GCTs (p=0.0095). A statistically significant correlation (p=0.0004) can be established between HER-2/neu status and clinical stage of the disease. Similarly, a significant correlation was observed between HER-2/neu overexpression and clinical outcome (p=0.0077). None of the specimens had definite HER-2/neu gene amplification. CONCLUSION: Our results suggest that HER-2/neu overexpression is associated with an adverse clinical outcome and has a prognostic role in testicular germ-cell tumors. Further studies are needed to evaluate the exact background of HER-2/neu overexpression in germ-cell tumors and the role of anti-HER-2/neu antibodies in the treatment regimens for this malignancy.
Subject(s)
Receptor, ErbB-2/biosynthesis , Teratoma/metabolism , Testicular Neoplasms/metabolism , Adult , Choriocarcinoma/genetics , Choriocarcinoma/metabolism , Choriocarcinoma/pathology , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Neoplasm Staging , Receptor, ErbB-2/genetics , Teratoma/genetics , Teratoma/pathology , Testicular Neoplasms/genetics , Testicular Neoplasms/pathologyABSTRACT
BACKGROUND: Lung resistance-related protein (LRP) was first detected in a non-P-glycoprotein-mediated multidrug-resistant lung cancer cell line and has been shown to be the major human vault protein. The aim of this study was to evaluate the expression of LRP in germ cell testicular tumors (GCT) and to determine the correlation between LRP expression and the clinical outcome of these tumors. PATIENTS AND METHODS: Seventy cases of primary testicular tumors were investigated. LRP protein was detected by immunohistochemistry and Western blotting methods. LRP mRNA was determined with RT-PCR. Patients' clinical parameters and tumor response to treatment were recorded. RESULTS: With immunohistochemistry, LRP was detected in 29 (41%) out of 70 primary testicular tumors. Twenty-two (63%) out of 35 tumors expressed LRP mRNA and LRP protein on examination by RT-PCR and Western blotting, respectively. Pure teratomas showed significantly higher LRP expression compared to other types of GCTs (p=0.0418). No relationship was demonstrated between the LRP immunostaining and stage of disease (p=0.2263). A significantly higher proportion of patients with LRP-negative tumors achieved complete response than those with LRP-positive tumors (p=0.0155). Patients whose tumors showed expression of LRP had significantly shorter overall survival (p=0.0428) than LRP-negative patients. CONCLUSION: Immunohistochemistry is a reliable method to evaluate LRP expression in testicular germ cell tumors. A positive correlation was found between LRP immunostaining and pure teratomas. LRP expression was associated with an adverse clinical outcome and shorter overall survival. Our findings suggest that LRP has prognostic value in testicular germ cell tumors and can predict clinical outcome.
Subject(s)
Germinoma/metabolism , Neoplasm Proteins/biosynthesis , Testicular Neoplasms/metabolism , Vault Ribonucleoprotein Particles/biosynthesis , Adolescent , Adult , Blotting, Western , Germinoma/genetics , Germinoma/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Proteins/genetics , Neoplasm Staging , Prognosis , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , Vault Ribonucleoprotein Particles/geneticsABSTRACT
BACKGROUND: Although the overexpression of the Epidermal Growth Factor Receptor 2 (EGFR-2, HER-2/neu, c-erbB-2) in malignancies might predict chemoresistance and poor prognosis, its clinical relevance has not been widely studied and determined in testicular tumors. PATIENTS AND METHODS: Since teratomas are relatively chemoresistant tumors, we evaluated the HER-2/neu receptor status of 28 primary testicular tumors (7 pure teratomas, 21 mixed germ cell tumors containing teratomatous components) using a standardized immunohistochemical method (HercepTest Kit). RESULTS: Seven (25%) out of 28 non-seminomatous germ cell tumors showed HER-2/neu positivity. The teratomatous components of mixed GCTs showed HER-2/neu overexpression in 5 cases. Three of the 5 choriocarcinoma components of mixed tumors overexpressed HER-2/neu. In one case (teratoma + choriocarcinoma) both components showed HER-2/neu overexpression. No HER-2/neu overexpression was detected in other, less differentiated histological subtypes. Among the HER-2/neu-positive cases, 3 patients are in complete remission, 3 patients are in partial remission and one patient died after primary chemotherapy. CONCLUSION: Twenty-five percent of the non-seminomatous germ cell tumors which contain teratomatous components overexpress HER-2/neu protein. The overexpression is restricted to the more differentiated histotypes. Further molecular investigations and clinicopathological studies are necessary to determine the correlation between HER-2/neu overexpression and clinical resistance of testicular tumors.
Subject(s)
Neoplasms, Germ Cell and Embryonal/metabolism , Receptor, ErbB-2/biosynthesis , Testicular Neoplasms/metabolism , Adolescent , Adult , Choriocarcinoma/drug therapy , Choriocarcinoma/metabolism , Choriocarcinoma/pathology , Humans , Immunohistochemistry , Male , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Seminoma/drug therapy , Seminoma/metabolism , Seminoma/pathology , Teratoma/drug therapy , Teratoma/metabolism , Teratoma/pathology , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Treatment OutcomeABSTRACT
PURPOSE: To examine the incidence, prognosis, clinical and histological characteristics, treatment, and outcome of patients with bilateral testicular cancer in the referral center in Hungary, to determine which parameters might predict a second testicular tumor. METHODS: . Clinical parameters-such as time of original surgery, histology of primary tumor, extent of the disease, serum marker concentrations, history of testicular abnormalities, treatment, response to treatment, follow-up period, data on second carcinoma-of bilateral testicular tumors among the 2,386 patients with testicular cancer treated between November 1988 and November 1998 were analyzed. RESULTS: The incidence of patients with synchronous testicular tumor was 0.8% (19 of 2,386 patients). The clinical stages were 8 I/A, 5 I/B, 1 II/A, 2 II/B, 1 III/A, and 2 III/B. Median follow-up time was 93 months and the 5-year overall survival was 84%. The incidence of patients with metachronous testicular cancer (median age 28 years and 35 years at first and second tumor diagnosis) was 2.2% (53 of 2,386 patients) and the median time to second tumor was 76 months (range 18-203 months). The clinical stages at the first and second tumor diagnosis were: 14 I/A, 21 I/B, 15 II/A, 2 II/B, and 1 III/B, and 26 I/A, 16 I/B, 3 II/A, 1 II/B, 7 III/B, respectively. The median follow-up time was 42 months and the 5-year overall survival was 93%. In thirteen patients with metachronous cancers, two family histories of testicular cancer, five cases of undescended testicles, seven cases of testicular atrophy, and one case of azoospermia were detected. There was a non-significant trend to a longer cancer interval after chemotherapy and radiotherapy and a tendency to a greater incidence of asynchronous seminoma after chemotherapy. Clinical stage I tumors were more frequent in the surveyed group than among patients not followed up according to the institutional protocol ( P = 0.01), but the survival rate was good in both groups. Seminoma as a second tumor was diagnosed in an older age group (median 38 years, range 25-49 years) than nonseminoma (median 32 years, range 21-51 years, P < 0.045). The interval till the appearance of a metachronous testicular cancer depended on tumor histology: in seminoma cases it was longer than in nonseminoma cases (median time: 121 months versus 50 months, P = 0.002). CONCLUSIONS: The overall incidence of bilateral testicular cancer in the referral center in Hungary was 3%. We could not identify clinical factors which predicted a higher risk for metachronous testicular cancer. With regular follow-up the early diagnosis of second testicular tumors is probable; therefore education, self-examination of the remaining testicle, and long-term follow-up are important in early detection.
Subject(s)
Germinoma , Neoplasms, Second Primary , Testicular Neoplasms , Adult , Biomarkers, Tumor/blood , Chemotherapy, Adjuvant , Chorionic Gonadotropin, beta Subunit, Human/blood , Germinoma/blood , Germinoma/epidemiology , Germinoma/pathology , Germinoma/therapy , Humans , Hungary/epidemiology , Incidence , Male , Middle Aged , Neoplasm Staging , Neoplasms, Second Primary/blood , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/therapy , Orchiectomy , Prognosis , Radiotherapy, Adjuvant , Risk Factors , Self-Examination , Seminoma/blood , Seminoma/epidemiology , Seminoma/pathology , Seminoma/therapy , Survival Analysis , Testicular Neoplasms/blood , Testicular Neoplasms/epidemiology , Testicular Neoplasms/pathology , Testicular Neoplasms/therapy , Treatment Outcome , alpha-Fetoproteins/metabolismABSTRACT
OBJECTIVE: To show the prevalence and determine the type of human papillomavirus (HPV) in healthy women of reproductive age in Hungary. STUDY DESIGN: We determined HPV nucleic acid using the Digene Hybrid Capture HPV-DNA assay from endocervical swabs of 1121 volunteer women of reproductive age. With the help of the hybridization antibody capture test we determined 14 HPV types (low risk, intermediate and high risk). RESULTS: HPV prevalence was 17.5% considering the whole material. At the Szeged center 27.6% of the women screened were HPV positive, whereas at the three centers in Budapest, HPV prevalence did not exceed 15% in either of them. With a cytological examination out of 1100 cases, 117 (10.6%) were found to be HPV infected. The virus infection could be shown out of 1018 non-malignant cytologies in 60 (5.9%) cases and from 82 epithelial lesions 57 (69.5%) were infected. The cytological and molecular HPV diagnoses showed a significant relation to each other (P<0.001). The cytological method showed HPV infections with a low degree of efficiency (sensitivity: 23.8%). On the other hand, the specificity (92.2%) is an acceptable method for the real negativity of the light microscopic HPV infection. CONCLUSIONS: These facts mean regarding the detection of HPV-DNA genoms that HPV positive cytological reports are false negative and in dysplasias are false positive. Since in HPV infected women the development of CIN is a great risk, it is advisable to carry out the HPV determination and typing in the so-called "endangered" groups.
Subject(s)
Genital Diseases, Female/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Tumor Virus Infections/diagnosis , Tumor Virus Infections/epidemiology , Adult , Cervix Uteri/pathology , Cervix Uteri/virology , Cytodiagnosis , DNA, Viral/analysis , Educational Status , Female , Humans , Hungary/epidemiology , Papillomaviridae/genetics , Sensitivity and Specificity , Sexual Behavior , Sexual Partners , SmokingABSTRACT
Germ cell testicular cancers are well-curable neoplasms, because total remission can be achieved in about 80% of the cases. However, 15-20% of the patients die due to drug resistance (DR). A number of mechanisms of the multidrug resistance phenotype are known, including MDR/P-glycoprotein (P-gp) and the so-called multidrug resistance associated protein (MRP). Lung Resistance Protein (LRP) is an ATP dependent membrane transporter protein associated with MDR. In our present work we studied the expression of LRP in testicular cancers. LRP expression was determined by immunohistochemistry (IH), Western blot (WB) and RT-PCR techniques. Clinical resistance was defined in accordance with the clinical oncologic rules. In 29 (41%) of 70 primary testicular tumours and in 22 (63%) of 35 cases, elevated LRP levels were established by IH and WB, respectively. In the latter 63%, the LRP mRNA levels were elevated as well. Six cases of the 15 seminomas and 23 cases of the nonseminomatous germ cell tumours (NSGCT) proved to be positive. No relationship was demonstrated between LRP expression and the stage of the disease. Despite the LRP positivity of 6 tumour samples, all of the seminomas proved sensitive. Of the 39 sensitive NSGCT, 27 cases were LRP-negative, whereas 11 tumour samples of 16 patients belonging to the resistant group proved LRP-positive (p=0.04). The authors concluded that the expression of LRP is responsible for clinical drug resistance in non-seminomatous testicular cancer patients.
Subject(s)
Biomarkers, Tumor/analysis , Drug Resistance, Neoplasm , Germinoma/chemistry , Neoplasm Proteins/analysis , Testicular Neoplasms/chemistry , Adult , Aged , Blotting, Western , Gene Expression Regulation, Neoplastic , Germinoma/drug therapy , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Proteins/genetics , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Testicular Neoplasms/drug therapy , Vault Ribonucleoprotein Particles/geneticsABSTRACT
PURPOSE: The authors analyze their 3-year results of the "educational and early detection program for testicular cancer". The goals of the program are to reduce the duration of symptoms and to improve early detection. METHODS: Advertisements were placed in the media describing the early signs of testicular cancer, the risks factors, the correct method of self-investigation and the importance of early detection. Between 1 April, 1995 and 1 April, 1998 5056 volunteers were examined. They underwent physical and ultrasound examination of the testicles, and in case of suspicious findings, tumor markers (alpha-fetoprotein, human choriogonadotropin) were checked. RESULTS: Testicular tumors were found in 1.28% of patients with symptoms (testicular enlargement or nodules). No tumor was found in the population that was symptom-free, or in patients with pain, sensitivity to palpation, or unrelated complaints. Of the patients with a palpable lump and swollen testicles, 4.5 and 3.9% were found to have tumors respectively. In total 32 testicular tumors were detected in 30 patients: 15 (2 bilateral) seminomas, 13 non-seminomas and 4 benign tumors. The occurrence of malignant testicular tumors was most frequent, 1.6% in the age group between 15 and 40 years. The stages were as follows: 9 I/A, 9 I/B, 1 I/S, 3 II/A, 1 II/B and 2 III/B. One patient was lost to follow-up after castration. All the other patients achieved complete remission. CONCLUSION: Despite the increasing incidence of testicular cancer screening of asymptomatic men does not lead to detection of tumors. The awareness of the early signs associated with cancer, self-examination, ultrasound examination of the testicle help in establishing an early diagnosis, nevertheless a widescale program for the early detection of testicular cancer is not justifiable. Effective early detection should be based on an educational program for the population at risk, the appropriate training of doctors and staff engaged in the health care of the young, and the initiation and facilitation of early ultrasound examination at the first symptoms. Serum markers play a limited role in early diagnosis.
