Morphological peculiarities of the autonomic nervous system in the thoracic region.

BACKGROUND: The aim of the work is to define the morphological peculiarities of the autonomic nervous system (ANS) in the thoracic region. MATERIAL AND METHODS: An anatomical study was performed on 20 cadavers, 17 men and 3 women. We studied cadavers within 24 h of death. We observed the vertebral and prevertebral section of the truncus sympathicus, their morphological peculiarities depending on the type of ANS. To show the intimate relationship of both systems, we also focused on the details of the structure related to the connections of the ANS with the spinal nervous system. RESULTS: In the thoracic region, the segmental arrangement of the truncus sympathicus ganglia prevailed in 16 (80%) cases. Rami communicantes gave anastomoses to spinal nerves. Small ganglia were observed on the rami communicantes to the spinal nerves. In the case of the concentrated type, in 4 cases (20%), we observed a reduction in the number of ganglia, as well as the absence of small ganglia on the connecting branches. Connections between n. vagus and sympathetic branches were poorly developed. We observed right-left asymmetry and differences in the formation of ganglia and anastomoses in the truncus sympathicus in the vertebral and prevertebral section. Variations of distance of n. splanchnicus major were observed in 16 cases (80%). CONCLUSION: This study allowed us to identify and describe the morphological peculiarities of the thoracic ANS. The variations were numerous; their preoperative diagnosis is difficult to impossible. The knowledge gained can be helpful in clarifying clinical signs and symptoms.

Expression of E-cadherin, Ki-67, and p53 in urinary bladder cancer in relation to progression, survival, and recurrence.

Although the incidence varies with age and gender, urothelial bladder cancer is a relatively frequently occurring malignancy with variable clinical behavior that often has high recurrence rates. In this study, we analyzed the tumor tissues of 224 patients with pTa, pT1, and pT2 urinary bladder cancer. We performed a histomorphologic analysis and immunohistochemistry for p53, Ki-67, and E-cadherin, which were selected as markers of the malignant process. For pTa and pT1, univariate analyses of cancer-specific survival (CSS), progression-free survival (PFS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method, the log-rank test and Cox regression. Multivariate analysis was performed by a Cox regression analysis. Ki-67 (P<0.001) was significantly associated with CSS, but the highest association was shown for E-cadherin (P<0.001). For pT1 and pTa, the Kaplan-Meier analysis and the log-rank test revealed significantly worse PFS for patients with higher levels of Ki-67 (P<0.001) and lower levels of E-cadherin (P<0.001). Based on these obtained results, it can be clearly stated that Ki-67 and E-cadherin expression levels are associated with CSS, PFS and RFS. The clinical utility of these markers is valuable for pTa and pT1 urinary bladder cancer and should be further verified with prospective multi-center trials.

Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells.

Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on γH2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in γ-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration.

[Molecular pathology of endometrial carcinoma - a review]. / Molekulová patológia endometriálneho karcinómu - prehlad.

Endometrial carcinoma (EC) is the most common malignancy of the female genital tract in developed countries. According to its histomorphologic characteristics EC is divided into endometroid and serous carcinoma; among less common subtypes there are clear cell, mucinous, neuroendocrine and undifferentiated carcinoma and carcinosarcoma. Endometroid and serous EC were essential for the so-called dual classification of EC (type I and type II), which considered mainly epidemiological, clinical and endocrine characteristics. It was shown that part of the high-grade serous carcinomas (type II) can develop from the endometroid EC by a multiplication of genomic changes and there are also EC, in which both basic types are overlapping. Today it is known that clinical and histological presentation of the EC reflects the genetic and epigenetic alterations affecting mainly PTEN, PIK3CA, KRAS, CTNNB1 and TP53 genes, or leading to microsatellite instability. However, these changes are variably present in both types of EC; therefore dual division of EC has appeared very rigid. The novel classifications should represent an integrated system which also incorporates the results of the gene expression analyses and multiparallel DNA sequencing. Based on these findings EC were divided into four molecular categories: a) POLE/ultra mutated; b) hyper mutated microsatellite instable; c) "copy number low" d) "copy number high" serous-like carcinoma. This division better reflects the biological characteristics of each EC and represents a base for the individual therapy.

mRNA expression pattern of retinoic acid and retinoid X nuclear receptor subtypes in human thyroid papillary carcinoma.

Retinoids have shown potential for the inhibition of tumour growth and progression. The objective of this study was to investigate retinoic acid nuclear receptor subtypes RAR/RXR and iodothyronine 5'-deiodinase, type I expression pattern in papillary thyroid tumour tissue of 26 patients in order to compare with those of the non-neoplastic thyroid tissue of the corresponding patients. The expression of selected parameters mRNA was examined by semi-quantitative RT-PCR. Papillary thyroid carcinoma (PTC) expressed RXRγ, when compared to non-neoplastic thyroid tissues of the corresponding patients that were lacking expression of RXRγ or its expression was very low. Moreover, we found significantly increased expression of RARα and RARγ in the overall group of PTC. This increase was detected in cases with positive lymph node metastasis (LNM), but not in cases with negative LNM. RARß was significantly reduced in the subgroup of classic variant (CV). We also detected absence or significantly lower expression of hDIO1 mRNA in tumour tissue when compared to non-neoplastic tissue in both overall PTC cases and in the CV subgroup. However, the significantly decreased levels of hDIO1 mRNA were detected in cases with negative LNM but not in cases with positive LNM when compared to corresponding non-tumour tissue in both overall PTC cases and in the CV subgroup. Differences in RAR and RXR subtype mRNA expression patterns in various PTCs may contribute to the immunochemistry data available, and may thus find exploitation in clinical oncology, particularly in the differential diagnosis of thyroid neoplasms.

Sertoli-Leydig cell tumor of the ovary--morphological and immunohistochemical analysis.

Sertoli-Leydig cell tumor is a rare and usually unilateral tumor of the ovary occurring in women's reproductive age. Only about 10% of these patients are over 50 years of age. One third of these patients are suffering from signs of virilisation. This work summarizes the morphological and immunohistochemical characteristics of this tumor in a 56-year old woman with clinical signs of virilisation.

Squamous cell carcinoma and piercing of the tongue - a case report.

Tongue piercings can be associated with local and systemic complications. Local complications occur frequently immediately after the surgery but also long-term local effects can cause problems such as speech and swallowing difficulties. Aspiration, transmission of infectious diseases, hypersensitivity reaction belong to the systemic complications. In the presented paper an unusual case of cancer development in a 26-year-old man who had a metal piercing inserted for 5 years in the right anterior third of the tongue. Despite of intense concommitant chemoradiotherapy the patient died 18 months from the first symptoms. In prevention of various complications it would be the best solution spread information about the risks of the tongue piercing especially within teenage population.

Relation between expression pattern of p53 and survivin in cutaneous basal cell carcinomas.

BACKGROUND: The tumor suppressor gene p53 is a key regulator of cell division and/or apoptosis. Survivin is a multifunctional member of the inhibitor of apoptosis family. Survivin and p53 represent diametrically opposed signals that influence the apoptotic pathway. MATERIAL/METHODS: To determine the role of p53 and survivin in basal cell carcinoma (BCC), we evaluated the expression pattern of both proteins with regard to the percentage of positively immunostained tumor cells, the intensity of staining, and subcellular localization among 31 subjects with BCC. RESULTS: Overexpression of p53 protein was found in 28 of 31 cases (90.3%), whereas survivin accumulation was seen in 27 (87.1%). For p53, moderate and/or strong immunoreactivity was seen in 20 of 28 cases (71.4%), and 26 of 28 cases (92.9%) showed more than 25% reactive tumor cells. Nuclear p53 staining was detected in 23 of 28 cases (82.1%), whereas combined nuclear and cytoplasmic localization was found in only 5 of 28 cases (17.9%). Survivin revealed mild intensity of immunoreaction in 22 of 27 cases (71%), and 25 of 27 cases (92.6%) showed less than 25% labeled tumor cells. Combined nuclear and cytoplasmic survivin localization was present in 26 of 27 cases (96.3%). Statistically significant differences were detected in the assessed expression parameters between those proteins. CONCLUSIONS: Our results suggest that overexpression of wild type p53 protein may suppress the expression of survivin and its antiapoptotic activity in BCC cells.

RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer.

Breast cancer is the most common cancer in women worldwide, representing 28.2% of all female malignancies. In addition to genetic changes, epigenetic events, as aberrant DNA methylation and histone modification, are responsible for cancer development. Many tumour suppressor genes are inactivated by DNA hypermethylation, which could be utilized for identification of new epigenetic biomarkers. To investigate the relation between DNA methylation level and breast cancer progression, we analysed DNA methylation in RASSF1A and CDH1 promoters using quantitative multiplex methylation-specific PCR in paraffin-embedded tumour tissues and blood samples from 92 breast cancer patients and 50 controls, respectively. The associations between RASSF1A and CDH1 methylation levels and clinico-pathological parameters were tested by Kruskal-Wallis and van der Waerden ANOVA tests. Out of 92 breast cancer patients, 76 (82.6%) manifested various levels of RASSF1A (range from 1.20 to 92.63%) and 20 (21.7%) of CDH1 (range from 1.20 to 79.62%) methylation. However, no methylation was found in 50 controls. Increasing trends in RASSF1A methylation were observed in tumour size, lymph node status and TNM stage, but only CDH1 methylation levels showed statistically significant differences between the patient subgroups in lymph node status and IHC subtype. Overall, stable relatively high RASSF1A methylation could be utilised as universal tumour marker and the less frequent but highly methylated CDH1 promoter can serve for identification of potentially metastasising tumours.

Endometrial cancer--prospective potential to make diagnostic process more specific.

OBJECTIVE: The incidence of carcinoma of endometrium in younger patients has increased tendency. Experimental data support that mutation of tumor suppressor gene TP53 plays an important role in endometrial carcinogenesis MATERIAL AND METHODS: Exons 2-11 of the gene TP53 into tissues of endometrial carcinoma and precancerous lesions were analyzed by DNA sequencing and restriction analysis. RESULTS: A polymorphism CCC/CGC at codon 72 was identified in exon 4 of TP53 gene of all precancerous lesions and carcinomas of endometrium. CONCLUSION: Our results also suggest presence of endometrial glandular dysplasia or serous histological type of endometrial carcinoma into examined samples. Given the course and prognosis of serous endometrial carcinoma, it is necessary and useful to identify this type of cancer in the mixed types of endometrial carcinomas. DNA analysis has potential to make diagnostic process more specific and affect to adjuvant therapy and survival of patients.

Congenital anomalies of the spleen from an embryological point of view.

The spleen is the major accumulation of lymphoid tissue in the human body, an organ which prenatally produces and postnatally controls blood cells. Normally, a developed spleen lies in the upper left quadrant in parallel with the long axis of the 10th rib. It is a mesodermal derivate which first appears as a condensation of mesenchymal cells inside the dorsal mesogastrium at the end of the fourth embryonic week. Some congenital anomalies of the spleen are common, such as splenic lobulation and accessory spleen, while other conditions are rare, such as wandering spleen and polysplenia. Splenogonadal fusion is also a rare developmental anomaly, resulting from abnormal fusion of the splenic and gonadal primordia during prenatal development. The purpose of this article is to describe the normal development of the human spleen, supplemented with our own photomicrographs and a review of congenital anomalies of the spleen with their possible embryonic basis.

Morphologic heterogeneity of human thymic nonlymphocytic cells.

The thymus is the central organ of the immune system. It is essential for the development and maintenance of normal immune system, especially cell-mediated immunity. From the morphological point of view, the thymus is divided into two main compartments, cortex and medulla. The thymic microenvironment consists of a network of reticular epithelial cells and other fixed and free cells. The microenvironment of thymus is very important for the selection and maturation of T cells. T cell differentiation occurs via T cell receptors. The major histocompatibility complex participates in interactions between T cells and thymic epithelial cells, in addition to interactions between T cells and dendritic cells, macrophages and myoid cells. The neuroendocrine system regulates early T cell differentiation by the transcription of neuroendocrine genes in the stromal network and expression of cognitive receptors by immature T cells. This work briefly summarizes morphological and ultrastructural characteristics of thymic epithelial cells, dendritic cells, macrophages and myoid cells. It is accompanied by the authors' own photomicrographs and electronmicrograph from a transmission electron microscope. All of these cells play a critical role in the proliferation, differentiation and selection of precursor cells in the T-cell lineage, but the precise mechanisms not well understudood.

Octuplet pregnancy following intracytoplasmic sperm injection and cryo embryo transfer.

BACKGROUND: It is well known that the frequency of multiple gestation increases after in vitro fertilization in which more than one embryo is transferred. The aim is to report an octuplet pregnancy following intracytoplasmic sperm injection and cryo embryo transfer. CASE REPORT: A 31-year-old woman and her 35-year-old husband, both Caucasian, complained of primary infertility. The intracytoplasmic sperm injection and cryo embryo transfer procedure was recommended as treatment. Ovarian stimulation was performed using recombinant follicle-stimulating hormone and human menopausal gonadotropin. Two embryos were transferred to the uterus. This fertilization cycle was unsuccessful. Three months later, cryo embryo transfer of two frozen/thawed embryos was performed, which resulted in pathological monozygotic octuplet anembryonic pregnancy. Two, and later eight, empty sacs were detected by sonographic examination. Cytogenetic examination revealed normal male karyotype. DNA analysis confirmed identical polymorphisms in all the gestation sacs, i.e. a monozygotic origin of all eight sacs. CONCLUSIONS: We report a rare case of octuplet pregnancy after intracytoplasmic sperm injection and cryo embryo transfer.

The phylogenesis and ontogenesis of the human pharyngeal region focused on the thymus, parathyroid, and thyroid glands.

The pharyngeal (branchial) region represents a classic example where the relationship between ontogenesis and phylogenesis has been demonstrated. It is a region where the development of gills during ontogenesis of all chordates has been recapitulated. In the process of evolution the pharyngeal region has undergone marked changes. While it functioned to ensure blood oxygenation and regulation of a constant internal environment in aquatic animals, it had to adapt to new and more complex functions in terrestrial vertebrates. The lungs have taken on the main role of blood oxygenation and the salivary glands now regulate ionic balance. The immune organs in mammals such as the thymus and the palatine tonsil, endocrine organs such as the parathyroid glands and the parafollicular cells of the thyroid gland, which produces calcitonin (originally as independent ultimobranchial bodies), as well as a part of the ear developed from the pharyngeal region. This article briefly summarizes the current knowledge regarding the phylogenesis and development of the human thymus, parathyroids, and the thyroid gland with a focus on the influence of neural crest cells during development.

Treatment of 1-methyl-1-nitrosourea-induced mammary tumours with immunostimulatory CpG motifs and 13-cis retinoic acid in female rats: histopathological study.

Histopathological evaluation of the mammary gland tumours of Sprague-Dawley rats induced with 1-methyl-1-nitrosourea (MNU), and treated with either CpG oligodeoxynucleotides (CpG-ODN) and/or 13-cis retinoic acid has been performed in this work. Since, the treatment of animals with CpG-ODN induced a significant decrease of tumour burden and volume in comparison with MNU treated control group (Macejova et al. 2001), it was of high impact to compare histological appearance of tumours in different experimental groups (MNU, CpG-ODN, 13-cis retinoic acid, CpG-ODN plus 13-cis retinoic acid). We have found reduced number of carcinomas with necroses in the CpG motifs treated group when compared to animals treated with MNU only. From the histological point of view the treatment with the CpG-ODN may have some protective effect. Carcinoma patterns proportion in the group treated with CpG-ODN was found to be different in comparison with other experimental groups. Treatment of rats with CpG-ODN had no apparent effect on invasiveness of developed carcinomas.

Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of c-erbB2.

CA IX is a tumour-associated carbonic anhydrase with proposed roles in pH modulation and intercellular communication. Its distribution was examined in normal, benign and malignant breast tissues and compared with expression of breast tumour markers including oestrogen receptor, c-erbB2, c-erbB3 and CD44. Tissue specimens were analysed using immunohistochemistry and/or reverse transcriptase-polymerase chain reaction (RT-PCR). CA IX was detected by IHC in 12/26 (46%) malignant tissues, 4/36 (11%) benign lesions, but not in 10 normal breasts. Staining was mostly confined to plasma membranes of abnormal epithelial cells, but in five cases was found in adjacent stroma. Semi-quantitative RT-PCR detected CA9 mRNA in 25/39 (64%) malignant tumours, 11/33 (33%) benign lesions, but in none of three normal breasts. Comparative RT-PCR analysis of malignant tissues revealed a relationship between CA9 positivity and c-erbB2 overexpression (p=0.05). Moreover, CA9-positive specimens displayed a significantly higher median level of c-erbB2 than CA9-negative ones (p=0.02). No significant association was found with the other markers. The results of this study support the possible importance of CA IX for breast carcinogenesis and suggest its potential use as a breast tumour marker.

Collagen type IV in epithelial tumours of colon.

Collagen type IV in the lamina propria mucosae is one of the main components of the basement membrane of normal and transitional colon mucosa. The aim of the present study was to assess the use of anti-collagen type IV antibodies in the evaluation of biological activity of epithelial tumours of the colon. Formalin-fixed and paraffin-embedded specimens of polyps and carcinomas of the colon from 14 patients were analyzed. In transitional mucosa around epithelial tumours, only minor deformities of the evenly thick collagen type IV-containing basement membranes were found. This pattern was different in polyps where collagen type IV-positive basement membrane components extended between basolateral membranes of epithelial cells. Local changes of collagen type IV positivity in basement membranes of polyps were observed. Positivity of epithelial basement membranes disappeared in adenocarcinomas but there was an increased positivity in fibrillar components of stroma. Basement membranes of microvessels in lamina propria mucosae were also positive for collagen type IV. Similar observations were made in the stroma of polyps. Our results indicate that loss of collagen type IV in basement membranes of adenocarcinomas is related to loss of differentiation and the malignant potential of epithelial tumours of colon.