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Katarzyna Uzdrowska,1 Narcyz Knap,1 Jacek Gulczynski,2 Alicja Kuban-Jankowska,1 Wiktoria Struck-Lewicka,3 Michal J Markuszewski,3 Tomasz Bączek,3 Ewa Izycka-Swieszewska,2 Magdalena Gorska-Ponikowska1 1Department of Medical Chemistry, Medical University of Gdansk, Gdansk, 80-211, Poland; 2Faculty of Health Sciences with the Institute of Maritime and Tropical Medicine, Medical University of Gdansk, Gdansk, 80-211, Poland; 3Faculty of Pharmacy, Medical University of Gdansk, Gdansk, 80-416, PolandCorrespondence: Magdalena Gorska-Ponikowska, Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St, Gdansk, 80-211, Poland, Tel +48 58 349 14 50, Fax +48 58 349 14 56, Email magdalena.gorska-ponikowska@gumed.edu.plAbstract: Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The “Technology and Innovation Roadmap” published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000– 1500 nm) is a better option than NIR-I (750– 1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.Keywords: graphene-based materials, oncological therapies, cancer treatment, biomedical innovations, drugs delivery systems

Introduction: Increasing data suggests a pivotal role of neural microenvironment in cancer development and progression. Perineural invasion (PNI) is defined as neoplastic infiltration of any nerve layer, epineurium, endoneurium or perineurium. In a set of malignancies it was proved to affect patients outcome usually as a predictor of poor prognosis. PNI incidence is various in different tumor types. Little is known about its incidence and role in non-small cell lung cancer (NSCLC). Material and methods: The study included 124 resected NSCLC cases from the patients operated between 2011 and 2012. Clinicopathological features were reviewed retrospectively. All available H&E sections taken during routine examination from the tumors were thoroughly examined to established pathologic characteristics such as histologic type, grade, pTNM, size of the tumor or vascular involvement. Results: Out of the all analyzed cases 57 (46.0%) were squamous cell carcinoma and 67 (54.0%) adenocarcinomas. PNI was identified in 17 (13.7%) tumors with at least one nerve affected. In one case more than 10 nerves were infiltrated. Additionally, vascular invasion (VI) was found in 39 (31.5%), spreading through air spaces (STAST) in 36 (29,0%) and pleural involvement (PI) in 66 (23.4%) cases. In a group of PNI positive cases most were squamous cell carcinomas (12/17, 70.6%) from which 5 (5/17, 29.4%), were poorly differentiated tumors (grade 3). In 9 cases (9/17, 53.0%) PNI coexisted with vascular invasion, in 3 (3/17, 17.6%) with STAS and in 8 (8/17, 47.1%) with PI. Conclusions: The study shows that PNI occurs in these type of tumor together with other features known as the indicators of worse outcome. The role of PNI is NSCLC is still unknown and needs careful investigation. [ABSTRACT FROM AUTHOR]

Background: This short review and pictorial essay presents a morphological insight into cancer neuroscience, which is a complex and dynamic area of the pathobiology of tumors., Methods: We discuss the different methods and issues connected with structural research on tumor innervation, interactions between neoplastic cells and the nervous system, and dysregulated neural influence on cancer phenotypes., Results: Perineural invasion (PNI), the most-visible cancer-nerve relation, is briefly presented, focusing on its pathophysiology and structural diversity as well as its clinical significance. The morphological approach to cancer neurobiology further includes the analysis of neural density/axonogenesis, neural network topographic distribution, and composition of fiber types and size. Next, the diverse range of neurotransmitters and neuropeptides and the neuroendocrine differentiation of cancer cells are reviewed. Another morphological area of cancer neuroscience is spatial or quantitative neural-related marker expression analysis through different detection, description, and visualization methods, also on experimental animal or cellular models., Conclusions: Morphological studies with systematic methodologies provide a necessary insight into the structure and function of the multifaceted tumor neural microenvironment and in context of possible new therapeutic neural-based oncological solutions.

Purpose: Neuropeptide Y (NPY) is a pleiotropic peptide, which is involved in many biological mechanisms important in regulation of cell growth and survival. The aim of this study was a comprehensive analysis of the NPY system in prostate pathology., Methods: The study was based on immunohistochemical analysis of NPY and its receptors, Y1R, Y2R and Y5R, in tissue samples from benign prostate (BP), primary prostate cancer (PCa) and PCa bone metastases. Tissue microarray (TMA) technique was employed, with analysis of multiple cores from each specimen. Intensity of the immunoreactivity and expression index (EI), as well as distribution of the immunostaining in neoplastic cells and stromal elements were evaluated. Perineural invasion (PNI) and extraprostatic extension (EPE) were areas of special interests. Moreover, a transwell migration assay on the LNCaP PCa cell line was used to assess the chemotactic properties of NPY., Results: Morphological analysis revealed homogeneous membrane and cytoplasmic pattern of NPY staining in cancer cells and its membrane localization with apical accentuation in BP glands. All elements of the NPY system were upregulated in pre-invasive prostate intraepithelial neoplasia, PCa and metastases. EI and staining intensity of NPY receptors were significantly higher in PCa then in BP with correlation between Y2R and Y5R. The strength of expression of the NPY system was further increased in the PNI and EPE areas. In bone metastases, Y1R and Y5R presented high expression scores., Conclusion: The results of our study suggest that the NPY system is involved in PCa, starting from early stages of its development to disseminated states of the disease, and participates in the invasion of PCa into the auto and paracrine matter., (© 2022. The Author(s).)

In this article authors would like to present the history of the "Neuropatologia Polska" journal (since 1994: "Folia Neuropathologica") in its first decade of existence. It outlines the circumstances surrounding the creation of the journal and shows how it evolved in the first years. The vast material analysed from the consecutive issues of the journal in the years from 1963 to 1972 was subjected to statistical and content analysis. From its first year, the journal has included works of a very high substantive level and a wide range of topics. The authors presented the results of contemporary research in many areas. The "Neuropatologia Polska" journal (later "Folia Neuropathologica") set paths for the development of neuropathology in clinical and experimental aspects. What is very important, it created a platform for international cooperation in many fields, included researchers and scientists from Western countries and foreign academic centres in difficult times. This article was created on the 60th anniversary of creation of "Neuropatologia Polska".

Neuropathological central nervous system (CNS) post-mortem examination is a highly specialistic element of the autopsy procedure with methodological specificity. Herein we propose updated recommendations for CNS autopsy for pathologists and neuropathologists. The protocol includes the compendium of neuroanatomy with current nomenclature, consecutive steps of gross examination, as well as appropriate sampling algorithms in different clinical and pathological settings. The significance of pathoclinical cooperation in differential diagnosis is exposed. We believe it is essential to create and promote the guidelines to improve the quality of CNS post-mortem examination at the national level.

The medical autopsy (also called hospital or clinical autopsy) is a highly specialised medical procedure, which requires professional expertise and suitably equipped facilities. To ensure high standards of performance, the Working Group of Autopsy Pathology of the European Society of Pathology (ESP) suggests a code of practice as a minimum standard for centres performing medical autopsies. The proposed standards exclusively address autopsies in adults, and not forensic autopsies, perinatal/or paediatric examinations. Minimum standards for organisation, standard of premises, and staffing conditions, as well as minimum requirements for level of expertise of the postmortem performing specialists, documentation, and turnaround times of the medical procedure, are presented. Medical autopsies should be performed by specialists in pathology, or by trainees under the supervision of such specialists. To maintain the required level of expertise, autopsies should be performed regularly and in a number that ensures the maintenance of good practice of all participating physicians. A minimum number of autopsies per dedicated pathologist in a centre should be at least 50, or as an average, at least one autopsy per working week. Forensic autopsies, but not paediatric/perinatal autopsies may be included in this number. Turnaround time for final reports should not exceed 3 weeks (14 working days) for autopsies without fixation of brain/spinal cord or other time-consuming additional examinations, and 6 weeks (30 working days) for those with fixation of brain/spinal cord or additional examinations., (© 2021. The Author(s).)

Introduction: Neuropathological brain and spinal cord post mortem examination is a distinct procedure that still plays an important role in modern medicine. In front of increasing amounts of clinical and genetic data, together with important developments in the field of neuroimaging, the Polish Association of Neuropathologists have updated their recommendations regarding central nervous system (CNS) examination. These guidelines are aimed at neuropathologists, pathologists and clinicians., Aim of the Study: Presentation of the outlined recommendations as their goal is to improve the quality, informativity, and cost effectiveness of CNS post mortem examinations. A comprehensive study of the literature was conducted to provide a clinical background of neuropathological autopsy. There are numerous open questions in neuroscience, and new strategies are required to foster research in CNS diseases. These include the challenge of organizing brain banks tasked with managing and protecting detailed multidisciplinary information about their resources. Complex neuropathological analyses of post mortem series are also important to assess the effectiveness of diagnostics and therapy, identify environmental impact on the development of neurological disorders, and improve public health policy. The recommendations outline the need for collaboration between multiple specialists to establish the proper diagnosis and to broaden knowledge of neurological disorders.

Background: Cancer stroma contains the neural compartment with specific components and action. Neural microenvironment processing includes among others axonogenesis, perineural invasion (PNI), neurosignaling, and tumor cell neural/neuroendocrine differentiation. Growing data suggest that tumor-neural crosstalk plays an important function in prostate cancer (PCa) biology. However, the mechanisms involved in PNI and axonogenesis, as well as their patho-clinical correlations in this tumor are unclear., Methods: The present study was carried out on FFPE samples of 73 PCa and 15 benign prostate (BP) cases. Immunohistochemistry with neural markers PGP9.5, TH, and NFP was performed on constructed TMAs and selected tissue sections. The analyzed parameters of tumor innervation included small nerve density (ND) measured on pan-neural marker (PGP9.5) and TH s4tained slides, as well assessment of PNI presence and morphology. The qualitative and topographic aspects were studied. In addition, the expression of neuroendocrine marker chromogranin and NPY was assessed with dedicated indexes. The correlations of the above parameters with basic patho-clinical data such as patients' age, tumor stage, grade, angioinvasion, and ERG status were examined., Results: The study showed that innervation parameters differed between cancer and BP. The neural network in PCa revealed heterogeneity, and ND PGP9.5 in tumor was significantly lower than in its periphery. The density of sympathetic TH-positive fibers and its proportion to all fibers was lower in cancer than in the periphery and BP samples. Perineural invasion was confirmed in 76% of cases, usually multifocally, occurring more commonly in tumors with a higher grade. NPY expression in PCa cells was common with its intensity often rising towards PNI. ERG+ tumors showed higher ND, more frequent PNI, and a higher stage. Moreover, chromogranin-positive cells were more pronounced in PCa with higher NPY expression., Conclusions: The analysis showed an irregular axonal network in prostate cancer with higher neural density (panneural and adrenergic) in the surroundings and the invasive front. ND and PNI interrelated with NPY expression, neuroendocrine differentiation, and ERG status. The above findings support new evidence for the presence of autocrine and paracrine interactions in prostate cancer neural microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sigorski, Gulczyński, Sejda, Rogowski and Iżycka-Świeszewska.)

This article constitutes a summary of the knowledge on the involvement of the nervous system in COVID-19, concerning its general pathobiology, clinical presentation and neuropathological features as well as the future directions of investigation. Variable definitions, selection bias, mainly retrospective analyses of hospitalized patients and different methodologies are implemented in the research of this new disease. Central nervous system (CNS) pathology presents most frequently features of non-specific neuroinflammation with microglial activation and lymphoid infiltrations, ischemic/hypoxic encephalopathy, acute cerebrovascular disease, and microthrombi. Some brain specimens remain unaffected or show only non-specific changes of the critical status. Interpretations of the neuropathological findings are not always balanced in a clinical context and discrepant in consequence. Designing of longitudinal neuropathological studies, more frequent autopsies, and building of COVID-19 brain banks, together with neuroimaging analyses is essential. Genetic predispositions or immunological factors corresponding to the disease profile as well as cerebrospinal fluid (CSF) or serum biomarkers of COVID-19, the impact of different virus variants and influence of the therapy need to be identified. The mechanisms causing neuroCOVID and cognitive impairment - whether they are infectious, toxic, vascular or metabolic - create other aspects under research. There are also many existential questions about post-COVID and delayed sequelae of the infection. The fight with pandemic is a challenge for the global society, with neuropathologists and neuroscientists as important allies in struggle for understanding and conquering COVID-19.

Here, we present a case that required a supplemental "old school" islet purification for a safe intraportal infusion. Following pancreas procurement from a brain-dead 26-year-old male donor (body mass index: 21.9), 24.6 ml of islet tissue was isolated after continuous density gradient centrifugation. The islet yield was 504,000 islet equivalent (IEQ), distributed among the following three fractions: 64,161 IEQ in 0.6 ml of pellet, 182,058 IEQ in 10 ml, and 258,010 IEQ in 14 ml with 95%, 20%, and 10% purity, respectively. After a 23-h culture, we applied supplemental islet purification, based on the separation of tissue subfractions during unit gravity sedimentation, a technique developed over 60 years ago ("old school"). This method enabled the reduction of the total pellet volume to 11.6 ml, while retaining 374,940 IEQ with a viability of over 90%. The final islet product was prepared in three infusion bags, containing 130,926 IEQ in 2.6 ml of pellet, 108,079 IEQ in 4 ml of pellet, and 135,935 IEQ in 5 ml of pellet with 65%, 40%, and 30% purity, respectively, and with the addition of unfractionated heparin (70 units/kg body weight). Upon the islet infusion from all three bags, portal pressure increased from 7 to 16 mmHg. Antithrombotic prophylaxis with heparin was continued for 48 h after the infusion, with target activated partial thromboplastin time 50-60 s, followed by fractionated heparin subcutaneous injections for 2 weeks. β-Cell graft function assessed on day 75 post-transplantation was good, according to Igls criteria, with complete elimination of severe hypoglycemic episodes and 50% reduction in insulin requirements. Time spent within the target glucose range (70-180 mg/dl) improved from 42% to 98% and HbA1c declined from 8.7% to 6.7%. Supplemental "old school" islet purification allowed for the safe and successful utilization of a robust and high-quality islet preparation, which otherwise would have been discarded.

The tumor microenvironment (TME) plays an essential role in the development and progression of neoplasms. TME consists of the extracellular matrix and numerous specialized cells interacting with cancer cells by paracrine and autocrine mechanisms. Tumor axonogenesis and neoneurogenesis constitute a developing area of investigation. Prostate cancer (PC) is one of the most common malignancies in men worldwide. During the past years, more and more studies have shown that mechanisms leading to the development of PC are not confined only to the epithelial cancer cell, but also involve the tumor stroma. Different nerve types and neurotransmitters present within the TME are thought to be important factors in PC biology. Moreover, perineural invasion, which is a common way of PC spreading, in parallel creates the neural niche for malignant cells. Cancer neurobiology seems to have become a new discipline to explore the contribution of neoplastic cell interactions with the nervous system and the neural TME component, also to search for potential therapeutic targets in malignant tumors such as PC., (© 2020 S. Karger AG, Basel.)

The wide scope of neuropathology is also connected to different systemic pathology findings. Neuroectodermal-type female genital tract lesions are not frequent. This article presents a short review of such entities in gynecological pathology and reports on two rare cases. The first described lesion is an endometrial glial polyp in a young woman. The second is a mature cystic teratoma accompanied by a peritoneal gliomatosis in an adolescent girl. Both presented entities posed diagnostic difficulties from the clinical and pathological perspective. They demanded careful sampling, immunophenotyping, as well as neuropathological consultation.

The article describes impact of advanced research in the USA and collaborative approach of US scientists and clinicians on development of the field of islet transplantation in Poland and all over the world. At the same time, it presents negative consequences of islet regulation by FDA as a biological drug leading to decline and extinction of the field in the US, while it is on the rise worldwide.

We present an analysis of two first historically documented limb body wall complex (LBWC) cases and our own contemporary perinatal autopsy series of this rare complex. So far it was supposed that the first case of this complex was reported in 1685 by Paul Portal. Studying the Joachim Oelhaf's autopsy report from 1613 with attached engraving showing the neonate with multiple birth defects led our research team to a conclusion that it was genuinely the first description of LBWC in the medical literature so far. We compared the Oelhaf's case from 1613 and the Portal's autopsy report from 1685 with our series of LBWC cases dissected in the Medical University of Gdansk between 1999 and 2011. Reviewing 1100 autopsy reports performed we encountered 9 cases of this unique complex. The analysis was supported by the literature review.

Between 1793 and 1914, there were many internationally recognised physicians active in Gdansk. Their scientific activities included, among other things, anatomopathological research, constituting a determinant of progress in medical sciences during this period. One of the most important people was Martin Heinrich Rathke (1793-1860). He is recognised as one of the founders of modern embryology. In Gdansk Rathke's successor was Wilhelm Baum (1799-1883). Baum introduced compulsory post-mortem examinations in the city hospital even after the outbreak, and he was mentor to Theodor Billroth (1829-1894). The successor of Baum as the head of the city hospital was Emil Friedrich Götz (1806-1858). He took up an important topic, which was the consent of the family of the deceased to perform an autopsy. Furthermore, it described the gradual broadening of the scope of anatomopathological activities, consistent with the postulates of the first and second Viennese school, performed in Gdansk in the nineteenth century. However, a detailed analysis of the relationship between the discoveries of nineteenth-century medicine, especially in the field of pathological anatomy, and research carried out in Gdansk, remains in the sphere of research to be done.

The second part of the comprehensive work concerning pathology museums and collections presents their history since the 19th century. The evolution and specialisation of museums, depending on the attitude of their creators and geographic localization, have been analysed. The changing aspects of obtaining the exhibits and how they were preserved, presented, and stored are also a part of this work. The methods of human organ fixation reached excellence in the 19th century, but the rarity of some pathologies urged the scientists to recreate them artificially in models for didactic purposes. In the 19th and 20th centuries one could observe the flourishing development with a plateau and then decline from the second part of the 20th century to the reorientation of the museums that took place in Europe and North America. The history of anatomopathological museums is connected with ethical problems related to acquisition of exhibits in previous centuries and especially during World War II. The changing purpose of the collections, as well as their unclear future and the impact on the visitors, are evident. For the last 50 years, many museums have been closing completely, but some collections have been digitalised and are still in permanent use. The uniqueness of old specimens with certain diseases, often long gone and not observed anymore, makes them important in many aspects nowadays. Pathology museums are themselves relics of the past, being at the same time tangible proof of ways of development in medicine, but also a way of preservation of human knowledge in a special type of relation with the human body.

Background: Endometrial cancer (EC) is a hormone-related disease, showing highly diverse features of ER/PR/HER2 status-based molecular subtypes. Long noncoding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) has recently emerged as a key molecule in many cancers, triggering epithelial-mesenchymal transition (EMT)-mediated cancer stem cell (CSC) formation, but little is known about its significance in EC. Thus, we aimed to investigate the clinical significance of HOTAIR itself in different molecular subtypes of EC and possible links between HOTAIR, EMT and CSC-related markers., Methods: The study group included 156 consecutive, stage I-IV EC patients treated between 2000 and 2010. ER, PR and HER2 protein expression were examined by immunohistochemistry (IHC) on tissue microarrays. RT-qPCR was used to analyze the expression levels of HOTAIR, EMT-related genes - SNAIL and SLUG - and the CSCs marker CD133., Results: Molecular subtypes, defined as ER/PR+HER2+, ER/PR+HER2-, ER-PR-HER2+ and ER-PR-HER2-, occurred in 40.2%, 52.3%, 4.7% and 1.9% of cases, respectively. The expression of HOTAIR did not differ between the subtypes, but high HOTAIR expression correlated with shorter overall survival (p = 0.04) in the entire group. The expression levels of HOTAIR, SNAIL, SLUG and CD133 were similar in defined EC molecular subtypes., Conclusions: Our data do not confirm the role of HOTAIR in EMT-mediated CSC formation in EC. Neither does the diversity of EC molecular subtypes influence these processes. But HOTAIR expression could serve as an independent prognostic factor in EC. The clinical importance of the above discoveries requires further studies.

We present a short history of anatomopathological museums in Europe. In the first part we provide an insight into the beginnings from the Renaissance until the middle of the 19th century. We assess forms of acquisition and exhibition of the specimens concerning the steps of medicine and pathology development. The prototypes were "curiosities of nature" collections starting in the 15th century. The next milestone collections focusing on the human body were those of Frederik Ruysch in the Netherlands (17th century). In the 18th century teachers in surgical and anatomical schools realized the educational power of such collections. Anatomopathology as a separate medical discipline was developing in parallel. At that time museums such as the one established by Honoré Fragonard in Paris, the Hunterian in Glasgow and Narrenturm in Vienna were created. At Polish universities in Cracow and Vilnius, such museums were beginning to emerge at the beginning of the 19th century. Anatomopathological collections became more popular, gathering specimens: osteological, dry and mummified, as well as wet - embedded in alcohol, formalin, and mysterious mixtures. They provide a wealth of important data for scientific, medical, historical and even ethical areas, as well as methods and concepts of conservation and even recreation of human body parts.

Four molecular subtypes have lately been established in endometrial cancer basing on estrogen receptor (ER), progesterone receptor (PR) and HER2 status: ER+/PR+/HER2+, ER+/PR+/HER2-, ER-/PR-/HER2+ and ER-/PR-/HER2-. The subtypes have shown diversity in terms of prognosis, clinicopathological and molecular characteristics, with ER+/PR+/HER2- and ER-/PR-/HER2+ group exhibiting exceptionally benign and aggressive behavior, respectively. We have further characterized the subtypes in the context of pathways known to drive endometrial carcinogenesis: phosphatidylinositol 3-kinase (PI3K)-AKT pathway (ERBB/PI3K pathway), TP53 system, and the mismatch repair (MMR) mechanism. Analysis of tumor heterogeneity was also included. ER+/PR+/HER2+ was characterized by active ERBB/PI3K pathway occurring in 58% of cases. Subtype ER-/PR-/HER2+ was characterized by the most frequent TP53 mutations (83% of cases). Triple negative phenotype utterly lacked active ERBB/PI3K pathway. Analyzed major pathways rarely correlated with clinicopathologial data but mutated TP53 and retained MMR did correlate with shorter overall survival (both P<0.01). The presence of tumor heterogeneity was most frequent in ER-/PR-/HER2+ subtype (53% of all cases). The presented results further emphasize that the molecular subtype distinction, along with MMR and TP53 status, could be a useful diagnostic tool in guiding individualized therapy.

Endometrial cancer (EC) is a hormone-dependent, most frequent malignancy of the female genital tract, yet no molecular subtype classification based receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) has been established so far. Assuming that molecular subtypes might differ fundamentally in EC, we analyzed expression levels of ER, PR, and HER2 with immunohistochemistry and aimed to determine clinical significance of four molecular subtypes: ER+/PR+/HER2+; ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2-. The study included 400 formalin-fixed paraffin-embedded primary tumor EC samples which covered all stages of endometrial carcinoma, from IA to IVB. ER-/PR-/HER2+ subtype correlated with the poorest outcome, ER+/PR+/HER2- subtype was associated with the most favorable prognosis (p = 0.002). Molecular subtype division remained an independent prognostic factor in multivariate analysis, accompanying parameters such as diabetes, hypertension, stage, myometrial infiltration, and metastases, all of which yielded hazard ratios between 1.39 and 2.23. ER+/PR+/HER2+ and ER+/PR+/HER2- subtypes had low average TP53 and TOP2A expression levels when compared with ER-/PR-/HER2+ and ER-/PR-/HER2- (both p < 0.00001). Molecular subtypes in EC do show diversity in terms of prognosis, clinicopathological, and molecular characteristics. ER-/PR-/HER2+ subtype exhibit is exceptionally aggressive tumor characteristics. Subtype differentiation might aid prediction of treatment response in EC., (© 2014 Wiley Periodicals, Inc.)

In this paper we would like to present probably the first surgery performed on the prostate gland followed by microscopic analysis of the obtained tumor tissue sample. We based on the existing correspondence between Ludwig von Hammen and Johann N. Pechlin, and their successors in this field as well. Von Hammen seems to be a pioneer in the area of not only urological surgery but in directing this part of medical practice from "lithotomists" to physicians, much better educated than barbers in physiology but first of all in anatomy. This 17th century physician from Gdansk tried to set new standards both for surgical medical practice but histopathological examination of the excised material as well. Due to the change of the operational skills and procedures von Hammen's work got almost forgotten, but remains remembered due to the work of historians of the medicine from following centuries., (© 2014 Wiley Periodicals, Inc.)

Objectives: The aim the study was to compare two groups of endometrial cancer patients (below and above 45 years of age) in the aspect of clinicopathological and molecular data., Material and Methods: The study encompassed 456 primary tumour samples retrospectively collected from a cohort of endometrial cancer patients, primarily treated by surgery Molecular analysis covered: copy number variations of 10 genes (TOP2A, ERBB1, ERBB2, ERBB3, ERBB4, MYC, CCND1, ESR1, PIK3CA, RAD21) analyzed by quantitative PCR; mRNA expression of 6 genes (SCGB2A2, RAD27, RUNX1, SNAI1, SNAI2, PROM1) analyzed with the use of reverse transcription quantitative PCR; protein expression analysis of 8 markers (PGR, ESR1; ERBB1, ERBB2, ERBB3, ERBB4, TOP2A, pAKT1) performed with the use of immunohistochemistry., Results: The younger group of patients was characterized by less frequent hypertension (p <0.00007), less frequent myometrial infiltration (p=0.002) and longer overall survival (p=0.003). Apart from RAD21 gene aberrations, which were more frequent in younger patients (p=0.02), the study revealed no statistically significant differences between the groups., Conclusions: The study showed no molecular differences in the profile of younger and older endometrial cancer patients. Data on both the prognostic and predictive significance of RAD21 in endometrial cancer are still insufficient. The clinical profile of younger patients with endometrial carcinoma was slightly better when compared to elderly patients. Younger patients were characterized by longer overall survival.

Intratumor heterogeneity implies heterogeneous protein function, facilitating tumor adaptation which results in therapeutic failure. We hypothesized that tumor heterogeneity at protein level may influence the course of the disease. As a single biopsy might not represent the full biologic complexity of the tumor, we have analyzed immunohistochemically four different cores obtained from each primary tumor within the cohort of 364 patients with endometrial cancer (EC). The following proteins were examined: estrogen receptor 1 (ESR1), progesterone receptor, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, receptor tyrosine-protein kinase erbB-3, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4, phosphatidylinositol-4,5-bisphosphate 3-kinase, phosphorylated v-akt murine thymoma viral oncogene homolog 1, v-myc avian myelocytomatosis viral oncogene homolog, DNA topoisomerase II alpha 170 kDa (TOP2A), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein p53, RAD21 homolog, S. pombe, and runt-related transcription factor 1. Particularly strong correlation was found between TOP2A and CDKN2A heterogeneity and higher stage of the disease (P = .0002 and P = .0003, respectively). Most correlations with clinicopathologic data were observed for ESR1 heterogeneity that correlated with non-endometrioid carcinomas (P=.02), higher stage (P=.005), grade (P=.01), and the presence of metastases (P = .01). Thirty-nine (11.0%) patients were classified as "globally heterogeneous". Cumulative tumor heterogeneity strongly correlated with the presence of metastases, higher stage, and higher grade of the disease (all P b .05). It also carried negative prognostic value (P=.0008). We show that the degree of heterogeneity in EC might serve as a clinically valid molecular marker., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

The molecular background of endometrial cancer (EC) has not been fully elucidated. In the present study, we developed a quantitative PCR (qPCR) platform to examine the gene dosages of the potential molecular markers MGB1, TOP2A, ERBB1-4, MYC, CCND1, ESR1 and PI3K. The platform was applied in samples collected from 157 EC patients (stage I-IV) to verify its clinical utility and to examine the diagnostic and prognostic significance of the analysed biomarkers. The gene dosage pattern of the ERBB family and its downstream effectors PI3K and MYC showed particularly strong correlations with clinicopathological data. The ERBB PI3K/Akt pathway was upregulated in 31 (20%) of 156 cases. Activation of the ERBB PI3K/Akt pathway was positively correlated with a higher stage (p=0.001), higher grade (p=0.001), histological type II disease (p=0.0003) and metastases (p=0.02). The implemented hierarchical clustering revealed that cluster 2 was characterised by high copy numbers of the studied genes. Cluster 2 was associated with shorter overall survival (p=0.05). The platform was found to be a fast and simple method for direct analysis of the genes involved in uterine carcinogenesis, making it feasible for EC biology characterisation.

We present the second part of our review concerning the history of autopsy. During the development of medicine the role of autopsy was obviously changing. Concurrently with the progress in the anatomical knowledge, the anatomists observed and noted both single anomalies and repetitive changes which correlated with symptoms in living patients. This is how anatomopathology came into being. We present the most famous people engaged in autopsy comprehension. We discuss main trends and ideas influencing the phenomenon of autopsy in the analyzed period: from sporadic public dissections, through theatra anatomica, introduction of autopsy to the hospital medicine and separation of anatomopathology as a medical speciality. The golden age of autopsy was the 19th century and the first half of the 20th century, with a consecutive decline in frequency. Nevertheless, despite the progress in diagnostics in vivo, it seems that autopsy will keep its important place in medicine according to the old motto "Mortui vivos docent" (the dead teach the living).

We present the first part of work concerning the history of autopsy. During the development of the pathology the role of autopsy was changing. The attitude towards the human body was often a result of struggles between human will to learn and religious beliefs. The knowledge was built upon religious procedures (mummification) through medical and surgical care of the victims of fights and wars and first autopsies. Until the 13th century dissections were seldom performed, sometimes in public. The aims varied from strictly scientific and practical (surgery) to artistic (human body in arts). Later on physicians were learning how to draw conclusions from autopsy results including malformations, pathologies, diseases, causes of death in order to try to put right diagnoses.

Objectives: We estimated the occurrence of DNA HPV 16 presence in lymph nodes of 25 patients undergoing abdominal operation for cervical carcinoma., Materials and Methods: The presence of HPV 16 DNA was detected during the preoperative diagnosis procedure by the PCR method., Results: According to the histopathological examination, metastases in the lymph nodes were present in material from two patients. It was confirmed HPV 16 DNA was detected with PCP. We found also 6 patients with HPV 16 DNA in their lymph nodes without histological confirmation., Conclusions: We consider PCR detection of HPV DNA as a simple and useful support of pathology diagnosis.

Objectives: We have estimated the incidence of human papilloma virus (HPV) DNA in cervical smears of patients with cervical carcinoma, treated in 1997-1998 at the II Department of Obstetrics and Gynecology, Medical University of Gdańsk, Poland., Materials and Methods: We have examined 107 patients suffering from cervical cancer. The HPV DNA was detected with the polymerase chain reaction (PCR) method using two primer pairs located in the E6, E7 open reading frames. HPV typing was executed by restriction fragments length polymorphism PCR (RFLP-PCR) method., Results: HPV DNA was detected in 75 (70.1%) patients. A group of patients with Ib (43%) and IIa (19.6%) clinical degrees made the highest percentage within the research group. We found no statistically significant differences between various clinical degrees of cervical cancer in the group of patients both HPV positive and negative., Conclusions: The frequency of HPV especially HPV 16 type infection incidence in cervical carcinoma is lower in Gdansk region than currently published.