GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested to be useful in the evaluation of carcinomas of ...mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. In this study, we examined normal developing and adult tissues and 2040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology, using monoclonal antibody (clone L50-823) and Leica Bond automated immunohistochemistry. GATA3 was expressed in trophoblast, fetal and adult epidermis, adult mammary and some salivary gland and sweat gland ductal epithelia, urothelia, distal nephron in developing and adult tissues, some prostatic basal cells, and subsets of T lymphocytes. It was expressed stronger in fetal than in adult mesothelia and was absent in respiratory and gastrointestinal epithelia. In epithelial neoplasms, GATA3 was expressed in >90% of primary and metastatic ductal and lobular carcinomas of the breast, urothelial, and cutaneous basal cell carcinomas and trophoblastic and endodermal sinus tumors. In metastatic breast carcinomas, it was more sensitive than GCDFP. Among squamous cell carcinomas, the expression was highest in the skin (81%) and lower in cervical (33%), laryngeal (16%), and pulmonary tumors (12%). Common positivity was found in skin adnexal tumors (100%), mesothelioma (58%), salivary gland (43%), and pancreatic (37%) ductal carcinomas, whereas frequency of expression in adenocarcinomas of lung, stomach, colon, endometrium, ovary, and prostate was <10%. Chromophobe renal cell carcinoma was a unique renal tumor with frequent positivity (51%), whereas oncocytomas were positive in 17% of cases but other types only rarely. Among mesenchymal and neuroectodermal tumors, paragangliomas were usually positive, which sets these tumors apart from epithelial neuroendocrine tumors. Mesenchymal tumors were only sporadically positive, except epithelia of biphasic synovial sarcomas. GATA3 is a useful marker in the characterization of not only mammary and urothelial but also renal and germ cell tumors, mesotheliomas, and paragangliomas. The multiple specificities of GATA3 should be taken into account when using this marker to detect metastatic mammary or urothelial carcinomas.
Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and ...they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.
The aim of this study was to analyze the occurrence of
TOP2A
gene amplification and chromosome 17 polysomy in patients with early breast cancer and to correlate the status of these alterations with ...the prognostic significance expressed as patients’ clinical features and survival. Such concurrent analyses of
TOP2A
gene status and chromosome 17 polysomy have not been performed before. Study group included 149 consecutive stage I-III patients administered standard multimodality treatment.
TOP2A
abnormalities were examined by standard fluorescence in situ hybridization (FISH) and developed by our group quantitative real-time PCR (qPCR).
TOP2A
amplification and deletion assessed by FISH were found in 23% and 7% of the tumours, respectively, and by qPCR in 31% and 11% of the tumours, respectively. Chromosome 17 polysomy was detected in 40% of the cases.
TOP2A
amplification (by qPCR) correlated with shorter disease-free survival (
p
= 0.03) and overall survival (
p
= 0.047), and the prognostic value of
TOP2A
was confirmed in the multivariate analysis (HR = 3.22, 95% CI 1.09–9.56,
p
= 0.03).
TOP2A
gene amplification, but not chromosome 17 polysomy, carries negative prognostic information in early breast cancer. Given the aforementioned results, qPCR might serve as a prognostic tool in determining the patient’s prognosis.
Sox10 transcription factor is expressed in schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. In addition, it has been ...reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 expression in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30 to 70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the gastrointestinal tract and in metastatic melanoma and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, perivascular epithelioid cell tumor and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell–type breast cancers, were only rarely positive but included 6% of squamous carcinomas of head and neck and 7% of pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.
Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. Despite relatively good prognosis a subset of patients ...shows recurrence, progression and/or metastatic disease, which requires additional treatment. However, neither prognostic nor predictive factors are well specified. Thus, we performed a literature search for the currently available data on disturbances in molecular pathways, cytogenetic changes and results gained by next generation sequencing (NGS) approaches in ONB in order to gain an overview of genetic alterations which might be useful for treating patients with ONB. We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). Furthermore, we compare high- and low-grade ONB, and describe its frequent mimicker: sinonasal neuroendocrine carcinoma. ONB is often a therapeutic challenge, so our goal should be the implementation of acquired knowledge into clinical practice, especially at pretreated, recurrent and metastatic stages. Moreover, the multicenter molecular studies are needed to increase the amount of available data.
Urothelial carcinoma (UC) of the urinary bladder is the second most common tumor in the field of urology and is characterized by a relatively aggressive growth behavior. New therapeutic approaches ...are required to improve the prognosis of affected patients. We hypothesized a link between dysregulation of eIFs and the development of UC. Therefore, in the present work, we investigated the expression behavior of eIF1, eIF1AY, eIF1AX, eIF2α, eIF3a, eIF3b, eIF4B, eIF4E, eIF4G, eIF5A, eIF5B, and eIF6 in UC compared with that in urothelial tissue.
Paraffin-embedded tumor tissue samples from 107 patients suffering from UC were examined. Seventy-six patients contained adjacent urothelial tissue. Three tumor tissue cylinders (tumor collective) and two urothelial tissue cylinders (control collective) were collected per patient and embedded in tissue microarray (TMA) blocks. Immunohistochemical staining of the TMA sections was then performed. The staining results were assessed semi-quantitatively. Staining intensities and immunoreactive scores (IRS) of both collectives were compared. In each case, a distinction was made between cytoplasmic and nuclear staining.
Significant up-regulation of eIF1AY, eIF2α, eIF3a, eIF3b, eIF4B, eIF4G, eIF5B, and eIF6 was found in the cytoplasm of UC. In contrast, eIF1 and eIF5A were significantly down-regulated in the cytoplasm of UC. eIF5A and eIF6 were significantly down-regulated in the nuclei of UC.
Dysregulation of eIFs in the urothelium of the urinary bladder is linked to carcinogenesis at this site.
Abstract
Background
Eosinophilic Esophagitis (EoE) has received increasing attention as a disease entity, and it is now recognized as an important disorder of the Upper Gastrointestinal Tract. ...Topical corticosteroids (tCS) are effective in clinical-pathological remission induction (RI) and remission maintenance (RM) of active EoE. With scoring systems, such as clinical (SDI), endoscopic (EREFS), and histological (EoEHSS) systems, EoE can be graded, and its disease activity can be assessed.
Objective
To discover how closely results within each of the three scoring systems SDI, EREFS, and EoEHSS are correlated between initial diagnosis (ID), RI, and RM, and to determine how well scores from the three systems are intercorrelated at each time point.
Methods
Retrospective cohort analysis of patients with active EoE was performed between 2006 and 2020, with follow-up for up to 6 years. SDI, EREFS and EoEHSS scores were recorded at ID, at RI, and in RM. Evaluation employed descriptive statistics, the Friedman test, and Bonferroni-corrected post hoc pairwise comparisons.
Results
At RI 29 and at RM 19 EoE patients provided data. Significant correlations were found between EREFS and EoEHSS at RI and in RM. Pairwise comparisons showed significant differences between ID and RI for SDI, for EREFS, and for EoEHSS.
Conclusion
The scoring systems tested did not show intercorrelation at ID. Comparison revealed significant differences for SDI, EREFS, and EoEHSS between the systems at ID und RI, but not in RM, during tCS treatment. These results underline the efficacy of tCS (at RI and RM) in the treatment of active EoE.
The paper presents Karhunen-Loeve Transform-based compression method, which can be applied to reduce the volume of data describing seabed topography. Developed algorithm allows for variable ...compression ratio and a possibility to limit the maximal reconstruction error. These properties have been introduced to the method because of the practical aspects of analysed problem. During the development, many experiments have been performed. The results presented in the paper show that the application of KLT in a conjunction with a set of so called common eigensurfaces gives high compression ratio for data representing seabed. In comparison to other well-known methods (Discrete Cosine Transform or Wavelet Transform based) the compression ratio is, in many cases, much higher. A novel solution for the problem of blank nodes occurrence and of storing irregular surface shapes is presented. The final compression algorithm presented here can become an important element of modern storage and management systems (handling vast data) that are used nowadays in maritime technology. Thanks to the open architecture, developed algorithm can be extended with other solutions aimed at seabed topographic measurement and visualisation.
The aim of this study was to find the relationship between active dynamic thermography (ADT) with cold excitation and burn depth. This new modality of evaluation of burns seems to be an attractive ...proposal for quantitative classification, allowing proper choice of burn wound treatment: conservative or surgical, especially compared with static thermography. The work was an in vivo experiment on domestic pigs, and a small number of patients were also diagnosed as part of the study. Statistical analysis showed a high correlation between the ADT synthetic parameter--thermal time constant, τ--and the classification of burn wounds that were predicted to heal within 3 weeks and so were treated conservatively and those that were predicted to not heal within 3 weeks and so were surgically treated. The results of the study show an accuracy of 60.7% for clinical evaluation, 69.6% for static thermography, 83.0% for ADT, and 84.0% for histopathologic assessment. The authors have concluded that the ADT method with cold excitation is suitable for the qualitative and quantitative assessment of burn depth.
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