Bilateral testicular germ cell tumors - 50 years experience.

OBJECTIVE: This study analysed the characteristics and outcome of the patients with bilateral germ testicular cell cancer (TC), especially synchronous. METHODS: Among 2.124 TC patients diagnosed between 1970 and 2020, 96 (4. 5%) developed the 2nd TC. Nine occurred synchronously and 87 were metachronous. Patients were analysed according to the age and histological type of bilateral TC in comparison with unilateral TC. RESULTS: The mean follow-up of all 2,124 patients was 14.9 years. Unilateral TC occurred in 2.028 patients (the mean age of 32.4 years), 707 of them had seminoma, 1.310 nonseminomatous (NS) TC and 11 spermatocytic tumours. The 1st tumour of metachronous bilateral disease was diagnosed at a significantly younger age (27.1 years) compared to the unilateral disease (32.4 years). The mean interval between the 1st and the 2nd TC was 8.2 years. Patients with NSTC had a longer mean interval (9.2 years) between the 1st and the 2nd TC in comparison with seminoma patients (6.7 years). The mean age at diagnosis for seminoma was significantly higher (31.3 years) compared to the NSTC (24.1 years). Bilateral seminoma occurred in 5 synchronous bilateral TC patients, four patients had discordant histology, none presented with bilateral NSTC. CONCLUSIONS: Bilateral TC is a rare and requires individualized management of patients (Tab. 5, Fig. 4, Ref. 32).

Ampullary cancer in a patient with familial adenomatous polyposis - a rare case report and current status of management.

Familial adenomatous polyposis (FAP) is an inherited autosomal dominant disorder. Extracolonic manifestations are seen quite often. As prophylactic colectomy has become a standard care in FAP patients, the concerns over the development of associated extracolonic malignancies have become more prevalent. The authors report a case of a patient with the history of subtotal colectomy because of FAP with the development of adenocarcinoma of papilla of Vater twenty-six years later. A radical procedure in form of proximal pancreaticoduodenectomy was indicated. Variable endoscopic surveillance protocols and treatment strategies have been proposed concerning the management of duodenal and periampullary lesions. In case of periampullary malignancies, the radical surgical resection offers the only chance for cure and the only option that may safeguard the long­term survival (Fig. 2, Ref. 30). Keywords: ampulla of Vater, bile duct, obstructive jaundice, pancreatoduodenectomy, periampullary tumors.

Idiopathic Granulomatous Mastitis - a new approach in diagnostics and treatment.

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking carcinoma and puerperal or non-puerperal mastitis. The primary purpose of this prospectively performed case control study was to compare clinical and imaging signs of IGM with the reference group of nonspecific, non- puerperal mastitis (NM) to identify the most typical clinical and imaging signs essential for a correct differential diagnosis. The secondary purpose was to present a new approach to non-invasive treatment. Thirty-nine women with histologically proven IGM and twenty-six patients with nonspecific mastitis underwent clinical examination, breast ultrasound (US), mammography (MG) and MRI examination. The most typical signs were selected for each group, and method and were statistically evaluated. The effectivity of colchicine, vitamin E and ribwort plantain tincture in treatment was assessed by clinical examination and imaging. Typical clinical signs of IGM included unilateral acute onset of breast edema, redness, palpable masses, missing fever, lymphadenopathy, no response to antibiotics or surgical interventions. Ultrasound revealed: "finger-like" structures (100%), ductectasias (76.9%), abscesses (76.9%), and lymphadenopathy (15.4%), while in MRI skin and tissue edema (100%), multicentric lesions (100%), abscesses (76.9%), ring enhancement (84.6%), lymphadenopathy (15.4%) and small enhancing lymph nodes (38.5%) were observed. Among the clinical signs, fistulas, hypoechoic mass, ductectasias and diffusion weighted images (DWI) restriction were significantly more frequent in patients with IGM than in those with NM. Treatment effectivity yielded 100% with a complete response between 6-19 months, depending on the disease extent. Targeted questions together with imaging can speed up selection for proper treatment with colchicine, vitamin E and local treatment. Long lasting use of antibiotics and repeated surgical interventions should be avoided.

Strumal carcinoid of the ovary - report of two cases and review of literature.

OBJECTIVE: Strumal carcinoid (SC) is a rare ovarian germ-cell tumour, which is characterized by a mixture of thyroid tissue and carcinoid. It can be presented as a monodermal teratoma or as a part of mature cystic teratoma (dermoid cyst). DESIGN: Case report. SETTING: Department of pathology, St. Elisabeth Cancer Institute, Bratislava. METHODS AND RESULTS: Hereby the authors describe two cases of this rare tumour in clinically asymptomatic women, 46- and 52-year-old, whom tumours were diagnosed at preventive gynaecological examination. The tumours considered of solid - cystic features, measured 65×45×40 mm and 75×45×40 mm and both contained parts of SC represented by tougher yellowish gelatinous areas. In both cases, SC was a part of the mature cystic teratoma (dermoid cyst), with predominated content. Histologically, both SC had a characteristic composition of intimate mixture of mature thyroid tissue and carcinoid. Immunohistochemically, the thyroid tissue stained positively with cytokeratin7, thyroglobulin and thyroid transcription factor-1, and the carcinoid component exhibited expression of synaptophysin and chromogranin A (only in one case). Tumour cells of both components of SC were negative for calcitonin and carcinoembryonic antigen. Both tumours showed low proliferation activity expressed by Ki-67 (up to 2%). Tumours were diagnosed in stage IA, and up to now are patients without any complications associated with tumours, free of relapse for 3 years and 6 months, respectively. CONCLUSION: SC represents an interesting form of primary ovarian carcinoid, which is usually asymptomatic and when confined to ovary, mostly has benign behaviour and can be treated by simple one-sided or bilateral adnexectomy. Keywords ovary, germ cell tumours, strumal carcinoid, immunohistochemistry.

Malignant Mesothelioma of the Tunica Vaginalis Testis. A Clinicopathologic Analysis of Two Cases with a Review of the Literature.

Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with only a limited number of reported cases. Its clinical differentiation is challenging, and its diagnosis is almost exclusively accidental. The major risk factor is exposure to asbestos, typically with a long latency between exposure and diagnosis. The current study presents the clinical data of two patients diagnosed with paratesticular malignant mesothelioma. We evaluated a large spectrum of risk factors in the patients histories. The histomorphological and immunohistochemical characteristics were analysed and put into the perspective of a broad differential diagnosis. Both cases of malignant epithelial mesothelioma of the tunica vaginalis testis clinically presented as unilateral hydroceles. Patients underwent surgery with the perioperative finding of a tumour. Radical inguinal orchiectomy was the treatment of choice for both patients. After comprehensive staging, the second patient underwent a second step of inguinal and pelvic lymph node dis- section. Follow-up visits revealed recurrence of the disease in the first patient. Resection of the tumour was performed. The histology confirmed the relapse of a tumour with identical features to those of the first tumour. Chemotherapy and radiotherapy were not indicated. Both patients are currently in complete remission. In conclusion, surgical treatment had a determinative role in the prognosis of these patients. Radical orchiectomy is the treatment of choice for localized disease. Lymph node dissection can be considered in the case of lymph node enlargement. There is a lack of evidence-based data for adjuvant chemotherapy and radiotherapy. Patients should be referred to experienced multidisciplinary cancer centres for a second opinion on histology, treatment, and a follow-up plan.Key words: mesothelioma - tunica vaginalis testis - hydrocele - asbestos exposure.

Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ.

BACKGROUND: Germ cell neoplasia in situ (GCNIS), is preinvasive stage of testicular germ cell tumours (TGCTs). Fibrillins, which are integral components of microfibrils are suggested to be involved in cancer pathogenesis and maintenance of embryonic stem cells pluripotency. The aim of this study was to examine fibrillin-1 (FBN-1) expression in TGCTs patients. METHODS: Surgical specimens from 203 patients with TGCTs were included into the translational study. FBN-1 expression was evaluated in the tumour tissue, in GCNIS and in adjacent non-neoplastic testicular tissue in all available cases. Tissue samples were processed by the tissue microarray method. FBN-1 was detected by immunohistochemistry using goat polyclonal antibody and the expression was evaluated by the multiplicative quickscore (QS). RESULTS: The highest FBN-1 positivity was detected in GCNIS (mean QS = 11.30), with overexpression of FBN-1 (QS >9) in the majority (77.1 %) of cases. Expression of FBN-1 in all subtypes of TGCTs was significantly lower in comparison to expression in GCNIS (all p <0.001). Seminoma had significantly higher expression compared to EC, ChC and TER (all p <0.05), but not to YST (p = 0.84). In non-neoplastic testicular tissue the FBN-1 positivity was very low (mean QS = 0.02). Sensitivity, specificity, positive and negative predictive value of FBN-1 expression for diagnosis of GCNIS were 97.1, 98.8, 98.6 and 97.7 %. CONCLUSIONS: FBN-1 is overexpressed in TGCTs and especially in GCNIS when compared to non-neoplastic testicular tissue in patients with germ cell tumors and could be involved in germ cell neoplasia in situ development.

Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors.

BACKGROUND: Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs. PATIENTS AND METHODS: Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome. RESULTS: None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including ≥3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression. CONCLUSIONS: In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.

Extremely rare tumour--malignant mesothelioma of tunica vaginalis testis.

INTRODUCTION: Malignant mesothelioma of tunica vaginalis testis is an extremely rare tumour. It is often caused by exposition to asbestos, however, more often its occurrence is sporadic. The diagnosis is usually set secondarily during hydrocele surgery. This type of tumour should be considered in cases with with atypical hydrocele, especially haematocele or atypical shape of seminal covering. RESULTS: A case of an asbestos-exposed patient with described disease and long-term hydrocele is presented. The number of patients is so small that the guidelines are limited due to low statistical power (Fig. 2, Ref. 14).

Management of clinical stage I testicular seminoma: active surveillance versus adjuvant chemotherapy.

PURPOSE: Surveillance after orchiectomy alone has become popular in the management of clinical stage I nonseminomatous germ cell testicular tumors (CSI NSGCTT), and adjuvant chemotherapy has been accepted in high-risk CSI NSGCTT. Because of the late toxicity of standard radiotherapy in CSI testicular seminoma (SGCTT), this therapeutic approach has been accepted also in the management of CSI SGCTT. In the current study, we analyzed single-center experience with risk-adapted therapeutic approaches (active surveillance and adjuvant chemotherapy) in patients with CSI SGCTT. PATIENTS AND METHODS: The study analyzed a total of 90 patients collected at a single center from April 2008 to March 2015 with CSI SGCTT who were stratified into two groups according to risk-adapted therapeutic approaches. RESULTS: In the group A (low-risk CSI SGCTT-no rete testis invasion, tumor size <4 cm, pT1 stage), which consisted of 74 patients who underwent surveillance, relapse occurred in seven (9.5 %) patients after a mean follow-up of 14.5 months. In the group B (high-risk CSI SGCTT-rete testis invasion, tumor size >4 cm or pT ≥ 2 stage), which consisted of 16 patients who were treated with adjuvant chemotherapy, relapse occurred in two (12.5 %) patients after a mean follow-up of 13.8 months. Overall survival of patients in both groups was 100 %. The statistically significant difference in progression-free survival between these two groups was not found. CONCLUSIONS: Radiotherapy is currently not recommended as an adjuvant treatment in CSI SGCTT patients. The benefit of using risk-adapted therapeutic approaches in CSI SGCTTs patients is evident.

Controversies in the management of clinical stage I nonseminomatous germ cell testicular cancer.

Surveillance after orchiectomy alone has become popular in the management of clinical stage I of nonseminomatous germ cell testicular tumors (CSI NSGCTT). Efforts to identify patients at high-risk of relapse led to a search for risk factors in CSI NSGCTT. The aim of the current study was to analyze longterm experiences with risk-adapted therapeutic approaches (active surveillance and adjuvant chemotherapy). From 1/ 1992 to 2/ 2015, a total of 454 CSI NSGCTT patients were included in the study and stratified into two groups according to risk-adapted therapeutic approaches. In Group A (low- risk CSI NSGCTT), which consisted of 287 patients who underwent surveillance, relapse occurred in 48 (16.7%) patients with a median followup of 7.0 months. Six patients (2.1%) of this group died with a median followup of 34.3 months. In Group B (high-risk CSI NSGCTT), which consisted of 167 patients who were treated with adjuvant chemotherapy, relapse occurred in two (1.2%) patients with a median followup of 56.2 months. One patient (0.6%) died 139.4 months following orchiectomy. Statistically significant difference in progression free survival between these two groups was found, but no significant difference in overall survival.Key words: testicular cancer -  surveillance -  adjuvant chemotherapy -  disease progression.

Management of patients with clinical stage I nonseminomatous germ cell testicular cancer: Active surveillance versus adjuvant chemotherapy - single-centre experience.

UNLABELLED: Surveillance after orchiectomy alone has become popular in the management of clinical stage I nonseminomatous germ cell testicular tumors (CSI NSGCTT). Efforts to identify patients at high risk of disease progression led to a search for risk factors in CSI NSGCTT. The aim of the present study was to analyse single-centre experience with risk-adapted therapeutic approaches (active surveillance versus adjuvant chemotherapy). From 1/1992 to 12/2013 a total of 431 CSI NSGCTT patients were included in the study and stratified into two groups according to risk-adapted therapeutic approaches. Group A (low-risk CSI NSGCTT) consisted of 276 patients who underwent active surveillance, progression of disease occurred in 46 (16.7%) patients with a median follow-up of 7.2 months. Six patients (2.2 %) of this group died with a median follow-up of 34.3 months. Group B (high-risk CSI NSGCTT) consisted of 155 patients who were treated with adjuvant chemotherapy, disease progression occurred in two (1.3 %) of them with a median follow-up of 56.2 months. One patient (0.6 %) died 139.4 months following orchiectomy. Overall survival rate of all CSI NSGCTT patients in both groups was 424/431 (98.4 %) with median follow-up of 130.4 months following orchiectomy. Surveillance policy is recommended only in patients with low-risk CSI NSGCTT. KEYWORDS: testicular cancer, surveillance, adjuvant chemotherapy, disease progression.

Ethnic disparities in breast cancer between Central Europe Caucasian women of Slavic origin and Middle East Turkish subjects.

The biological, cultural, behavioral and sociodemographic differences across populations modulate breast cancer profile among races or ethnics. Following this, we aimed to identify differences in breast cancer epidemiology, histopathology, and clinical presentation from representatives of central Europe (Slovakia) and Middle-East countries (Turkey) to point on ethnic disparities in cancer biology. The population based cross-sectional study analyzing 414 cases of primary breast carcinomas where 214 represented Caucasian and 200 Turkish subjects. The differences were found for age at the time of diagnosis (<0.0001), education, menopausal status (<0.001), tumor localization (<0.01), size (<0.0001), grade (<0.05) and axillary lymph node status (<0.001) between groups. Although carcinomas in Slovak subjects were of higher grade, negative axillary nodal status was more frequent finding compared to Turkish patients (50.0 vs. 41.0%). The Slovak group showed carcinomas to be more often ER positive (72.4 vs. 54.0%; <0.001), ER/PgR positive (54.6 vs. 49.0%; <0.001), of better Nottingham prognostic index (<0.001), and less frequent Her-2 positive (21.2 vs. 28.5%). Slovak population expressed significantly higher risk of non-sentinel lymph node metastases with increased tumor size, grade, vascular invasion and Her-2 positivity compared to Turkey population. The tumor size >2 cm and high tumor grade (G3) bears a risk of OR=7.62 and OR=3.10 in Slovak compared to OR=3.94 and OR=1.79 in Turkish cases, respectively.There are wide demographic and biological disparities in breast cancer between observed ethnics providing unique information for clinicians working at the level of screening or therapy in these populations.

Immunohistochemical characterization of urothelial carcinoma.

From the archive of BB Biocyt company, 32 urinary bladder carcinomas (urothelium carcinomas, UC) and 7 cases of chronic cystitis were selected and examined in semiserial sections for the following antigens: 1) cell proliferation marker Ki-67 (expressed in the nuclei), 2) cell cycle regulator p16/INK4a polypeptide (expressed in the cytoplasm and nuclei), 3) urothelium marker p63 (expressed in the nuclei), 4) cytokeratin 7 (CK7). 5) cytokeratin 20 (CK20) and 6) high molecular weight cytokeratin (HMWCK). Invasive urothelium carcinomas showing a high grade dysplasia (invasive HG UC) comprised over the half (20 out of 32) of the investigated tumours. Microinvasion to lamina propria (seen in three HG papillary carcinomas) was regarded as an early infiltration even when the position of muscular layer could not be determined. Classical invasion across the urinary bladder wall and/or to surrounding tissues was found in 17 cases of low-differentiated HG UCs. The rest (9 out of 32 neoplasms) were either non-invasive papillary carcinomas of high (non-invasive HG UC, 5 cases) or low malignant potential (noninvasive LG UC, 4 cases). Finally, 3 cases were papillary urothelium neoplasms of low malignant potential (PUNLMP). HMWCK was present in all invasive tumours, whereas the frequency of other urothelium markers ranged from 65 to 88 %. Nevertheless, at least two markers were expressed in each invasive tumour. Staining for Ki-67 antigen was positive in over 50 % of the nuclei of HG UCs, while in the LG UCs, the frequency of positive Ki-67 staining did not exceed 25 %. In PUNLMP, the positive rate of Ki-67 stained dysplastic cells was below 10 %. The staining for p16 antigen did not correlate with the degree of dysplasia within urothelium tumours. For routine diagnostic, we recommend to combine the Ki-67 staining with detection of HMWCK. In cases of chronic cystitis, which developed urothelial hyperplasia and/or squamous metaplasia, the presence of p63 antigen was a relevant marker confirming the urothelial origin of the altered transitional cells (Tab. 6, Fig. 4, Ref. 69).

[Expression of carbonic anhydrase IX in the breast carcinomas]. / Expresia karbonickej anhydrázy IX v karcinómoch prsníka.

OBJECTIVE: Carbonic anhydrase IX (CA IX) is one indicator of hypoxia in the tumor and its expression is associated with more aggressive forms of breast cancer. The aim of this study is to point out its own set of correlation between CA IX expression and selected morphological and biological indicators. TYPE OF STUDY: Cohort prospective study. SETTING: Department of Pathology of Slovak Medical University and St. Elisabeth Cancer Institute, Bratislava, Slovak Republic. METHODS: These were 145 cases of breast cancer aged 25 to 85 years (median 59 years) from the Register of the Institute of Pathology and Slovak Medical University and St. Elisabeth Cancer Institute in Bratislava for the period 1. 9. 2012 to 28. 2. 2013. In all cases were examined CA IX, estrogen receptor (ER), progesterone receptor (PR), HER2, p53 and Ki67 by immunohistochemistry. Typing, grading and staging of the disease were evaluated according to the classification systems currently in place. RESULTS: CA IX expression was demonstrated in 51 cases (35.2%). CA IX positivity correlated with the degree of differentiation (p = 0.0001), with ER status (p <0.0001) and PR (p <0.01) and HER2 (p <0.01) and proliferative activity as measured by Ki67 (p <0.001). HER2-positive cancers and triple-negative cancers were more frequently associated with the expression of CA IX compared with luminal subtypes (p <0.0001). The state of CA IX and age range of the tumor - pT and lymph node status - pN and p53 have not been shown statistically significant correlations. CONCLUSION: CA IX examination in breast cancer provides valuable information on the state of hypoxia in the tumor, thereby supplementing view of prognosis of the disease.

Rosiglitazone shows partial oncostatic effect in rat mammary carcinogenesis.

Peroral antidiabetics from thiazolidinedione (glitazone) group showed oncostatic effects in preclinical models. This study evaluated chemopreventive effects of rosiglitazone in N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. N-methyl-N-nitrosourea was administered in two intraperitoneal doses each per 50 mg/kg b.w. between 40th and 51st postnatal days. Rosiglitazone was administered in a diet at a concentration of 10 ppm and 100 ppm, respectively, 9 days before the first carcinogen dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors and estimation of latency period, tumor frequency per group and animal, and tumor volume were recorded. The experiment was terminated 16 weeks after the first carcinogen dose, basic tumor growth parameters and selected metabolic and hormonal variables were evaluated. Chemoprevention with higher rosiglitazone dose decreased tumor frequency per group by 44%, other tumor parameters (incidence, tumor frequency per animal) were decreased insignificantly (at both doses), latency period was not changed. Rosiglitazone administration decreased cumulative tumor volume, more efficiently at lower dose. Glycaemia and insulinaemia decreased after lower rosigitazone dose administration but glycaemia did not exceed normal values. Higher rosiglitazone dose alleviated some metabolic alterations resulting from cancer progression more effectively but induced a prominent cardiac hypertrophy.

Paratesticular mesothelioma in young age. Case report.

BACKGROUND: Malignant mesothelioma is a neoplasm arising in serosal membranes in the body cavities. Usual presentation of the tumor is in the pleura, peritoneum and less frequently pericardium. Paratesticular mesothelioma is the rarest known form of malignant mesothelioma with only a limited number of reported cases. CASE: A case of malignant epithelial mesothelioma of the tunica vaginalis testis was reported with presentation of hydrocele and multinodular intrascrotal masses in a 20-year old male. The patient underwent surgery for post-traumatic long-term hydrocele with perioperative discovery of multiple small exophytic structures. After histological findings of the malignant mesothelioma of tunica vaginalis testis, he underwent left-side orchiectomy, followed by inguinal and pelvic lymph node dissection. Clinical staging did not reveal distant metastases. Regular follow-up visits based on physical examinations and imaging studies are to date negative for recurrence. CONCLUSION: Literature data were reviewed, and possible risk factors for the development of the neoplasm were analysed.

[The p16INK4A mRNA transcripts estimation in cervical smear with different degrees of cervical dysplasia]. / Stanovenie expresie p16INK4A mRNA transkriptu v steroch z krcka maternice s rôznymi stupnami cervikálnej dysplázie.

OBJECTIVE: To determine the presence of HPV infection and expression level of p16INK4A mRNA transcripts in cervical smears as adjunct biomarker in detection of cervical intraepithelial neoplasia or cancer. DESIGN: Prospective pilot clinical study assessing clinical utility and validity of ddCt method for qPCR mRNA expression of p16ink4a in comparison to immunohistochemistry. SETTING: Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. METHODS: Cervical smears (OC) from patients with different cervical lesions (L-SIL, H-SIL, SCA; n=45) and from healthy controls (n=45) were tested for the presence of HPV infection and p16INK4A mRNA transcripts using relative quantification (RQ). Results were compared to H&E and IHC histological findings from biopsies (conization, hysterectomy). RESULTS: HPV 16 was the most frequent finding (53.3%) in the group of subjects with cervical dysplasia. The p16INK4A mRNA expression analysis revealed the slightly reduced expression in L-SIL group, 4-fold increased expression in H-SIL and 10-fold increase in women with SCA when compared to controls. The p16INK4A mRNA expression in OC was present in 30% of L-SIL, 75% of H-SIL and 85.7% of SCA samples, respectively. The test overall sensitivity was 81.48% (95% CI: 61.92-93.7) and specificity 60% (95% CI: 26.24- 87.84) with PPV of 84.62% and NPV of 54.55%. The likelihood ratio (LR) in case of test positivity was 2.04 and for negativity 0.31. The diagnostic accuracy of p16INK4A expression by RQ method in OC smears for prediction of p16 positivity in cervical dysplasia was 66.7% for the L-SIL lesions, 59.5% for H-SIL lesions, and 100% for SCA (r=0.9897, p<0.0913) when compared to IHC p16 positive findings in surgically treated samples. CONCLUSION: The relative quantification is able to determine the level of p16INK4A mRNA transcripts in cervical smear cells with active carcinogenesis nearly at the same level as IHC staining. The advance of biopsy sparing over IHC is qualifying this diagnostic approach for useful candidate in selective management of women with cervical dysplasia looking for cervix preservation or avoiding the unnecessary overtreatment.

Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment.

The results of experimental studies have indicated the pleiotropic effects of statins in organism, e.g. the influence on cell cycle, apoptosis or angiogenesis. In this study, the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined. Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment (18 weeks). At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis. In treated animals (simvastatin 180 mg/kg), significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation. Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells. In high grade control carcinoma cells, the expression of Ki67 increased by 37% (non-significantly) in comparison with control low grade carcinomas. A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment. The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment.

Melatonin enhanced bexarotene efficacy in experimental mammary carcinogenesis.

The aim of this paper was to test lower, safe bexarotene dose administered alone and in combination with melatonin to improve its efficacy. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea in female Sprague-Dawley rats, administered in two doses intraperitoneally between 42.-54. postnatal days and chemoprevention was initiated 7 days prior to first N-methyl-N-nitrosourea injection and lasted 15 weeks. Bexarotene, particularly in combination with melatonin decreased mammary tumor incidence and frequency with a shift from poorly to well differentiated carcinomas. Bexarotene alleviated glycaemia and liver/heart muscle glycogen concentration decreased as well as liver/thymus malondialdehyde increased in comparison with control group. The combination of bexarotene and melatonin is therefore beneficial in preventive-curative model of experimental mammary carcinogenesis and may be applied in oncological practice as such.

Correlations of survivin expression with clinicomorphological parameters and hormonal receptor status in breast ductal carcinoma.

The antiapoptotic protein survivin is widely expressed in most human cancers, including carcinomas of the breast. It is rarely detected in corresponding normal adult tissues. Therefore, survivin comes into the limelight as a promising diagnostic biomarker and prognostic parameter. Immunohistochemically, we examined the expression of this protein in 126 cases of ductal breast carcinoma to determine the association with clinicomorphological parameters such as age of patients, grade, stage and size of the primary tumor, lymph node metastasis, vascular invasion as well as estrogen and progesterone status. In each section, the subcellular location of survivin antigen, the intensity of staining and the percentage of labeled cells were assessed. Overall, survivin was expressed in 111 cases (88.1%). The statistical analysis revealed a significant correlation between the nuclear location of survivin and tumor grade 3. Furthermore, a significant relation was also found between vascular invasion and nuclear and combined nuclear and cytoplasmic survivin expression, together with a higher intensity of immunoreaction. However, no significant correlations were shown with other clinicomorphological parameters, such as stage and size of the tumor, lymph node metastasis, estrogen and progesterone receptors and age. Our findings revealed that survivin was frequently overexpressed in carcinoma cells, where it was present in different subcellular compartments. The nuclear positivity of survivin or combined nuclear and cytoplasmic expression was shown to be a poor prognostic parameter in ductal breast carcinoma.