Immunoexpression of Claudins -3, -4 and -7 in prostate adenocarcinomas.

Claudins are a family of essential tight junction proteins, abnormally expressed in human carcinomas. The studies that indicated the involvement of claudins in tumor biology and progression suggest the possibility of their utility as markers for diagnosis or prognosis, but also as possible targets for therapy. We investigated 50 prostate adenocarcinomas (PAs) for which we followed the expression of Claudins -3, -4 and -7 in relation to International Society of Urological Pathology (ISUP) grades. We observed the positivity for Claudin-3, Claudin-4, and Claudin-7 in 76%, 74% and 46% of cases. Analysis of the immunoexpression pattern revealed the cytoplasmic and nuclear translocation for Claudins -3 and -4, and only cytoplasmic for Claudin-7. For all claudins investigated, we noted a final staining score with significantly higher values or at the limit of statistical significance for PA belonging to ISUP groups 1-4. The internalization of Claudins -3, -4 and -7 expression, regardless of the degree of PA, indicates their involvement in prostate carcinogenesis. In addition, the similar immunoexpression patterns of the three investigated claudins and their positive linear correlation suggest a coordinated regulation and indicate the possibility of a targeted treatment strategy.

Head and Neck Low Grade Chondrosarcoma-A Rare Entity.

Chondrosarcoma represents approximately 0.1% of all neoplasms of the head and neck and is considered a rare disease with a relatively good prognosis. The 5-year overall survival (OS) rate is estimated at 70-80%, being considered a disease with a low growth rate. Approximately 13% of all cases of chondrosarcoma are located in the region of the head and neck. We present the case of a 30-year-old patient without a medical history who reported dysphagia, swallowing difficulty, neck mass sensation and dysphonia that started insidiously after an upper respiratory tract infection. Subsequently, the patient was diagnosed with a low-grade glosso-epiglottic region chondrosarcoma and was multimodally treated with surgery followed by chemotherapy and radiotherapy. The radiation treatment was delivered with a Rokus M40 former Soviet Union cobalt machine without any image guidance capabilities. The inability to obtain resection margin information justified an aggressive adjuvant treatment with chemotherapy and radiotherapy. The early loss from the oncological record without recurrence of the disease could be associated in this case with the consequence of a major complication, of which we could assume an aspiration pneumonia secondary to a dysphagia associated with an aggressive multidisciplinary treatment. Large tumor size and positive resection margins (R1 resection) are risk factors that support an intensive adjuvant approach in order to reduce the risk of recurrence, but the low grade of tumor associated with a lower risk of recurrence as well as the adverse events (AE) of adjuvant radiotherapy and chemotherapy justify a more reserved therapeutic approach. Taking into account the longer life expectancy of these patients, it is recommended to use a more conformal irradiation technique in order to reduce doses to radiosensitive structures as well as to omit elective neck irradiation, taking into account the lower risk of lymph node involvement. The lack of guidelines, which include very rare tumors including low grade chondrosarcoma of the head and neck, makes a unified approach difficult, but the data presented in case reports could contribute to choosing the regimen that offers the best therapeutic ratio.

Statical Association between Clinical and Histopathological Parameters for Keratinocyte Carcinomas.

The most common tumor of the western world is comprised of forms of non-melanoma skin cancers, previously known as keratinocyte carcinomas (KCs) The purpose of this study was to determine de incidence of non-melanoma skin tumors and the relationship between histopathological risk factors in patients with skin cancers. The study was composed from 332 cases of skin malignancies for which clinical and histopathological aggressivity factors were statistically analyzed through comparison tests and also stored digitally. For basal cell carcinoma (BCC) statistical analysis indicated significant relationships between pT category and gender, tumor size, ulceration, depth of invasion and positive resection limits. For squamous cell carcinoma (SCC) statistical analysis indicated significant relationships between pT category and tumor size, depth of invasion and positive resection limits. Clinical and histological analysis of certain characteristics of the above-mentioned skin cancers is an essential step in documenting and improving both prognosis and therapy standards.

VEGF Immunoexpression in Endometrioid Endometrial Carcinomas.

Vascular endothelial growth factor (VEGF) is the most important stimulator of endometrial tumor angiogenesis, a mechanism that may be a therapeutic target in the context of an incidence and persistent mortality of endometrial endometrial carcinomas (EEC). In this study, VEGF immunoexpression was analyzed for 50 cases of EEC in relation to the histopathological parameters of tumor aggressiveness. High VEGF scores have been associated with the high grade and advanced stage of EEC, but unrelated to the depth of myometrial invasion, the pattern of tumor invasion, or vascular invasion. VEGF may be useful for assessing EEC aggression, but also for tumor angiogenic potential, which recommends it as a possible mark for specific antitumor therapy.

Snail Immunoexpression in Endometrioid Endometrial Carcinomas.

Endometrial carcinoma is one of the most prevalent cancers affecting women with epidemiological placing it as the sixth most common cancer in women. One of the factors implicated in EMT (epithelial-mesenchymal transition), Snail is regarded as having a pivotal role. We selected a number of 30 endometrial carcinomas, in a 2-year period (2020-2022). Snail immunoexpression was identified in the tumor cells for 70% of the endometroid carcinoma cases studied. Tumor cells showed both nuclear and cytoplasmic expression but only nuclear signals were quantified. The average percent of marked tumor cells was 38.6±24.9, corresponding to well differentiated carcinomas. Our analysis also showed a significant association between higher tumor grade and snail expression (p=0.000). Alteration of the epithelial-mesenchymal phenotype in endometrial carcinomas by Snail overexpression in high-grade and advanced-stage lesions constitutes mechanisms involved in the process of tumor progression.

Ezrin Immunoexpression in Prostate Adenocarcinomas.

Ezrin is a component of cell surface structures, the most important member of the Ezrin/radixin/moesin family. In this study, we aimed to evaluate the expression of ezrin in 50 cases of prostate carcinoma (PA) in relation to the ISUP (International Society of Urological Pathology) groups. Ezrin expression analysis was identified in 78% of the PA cases investigated, with predominantly cytoplasmic staining pattern and variable intensity. Overall, we observed an increase in the intensity of the immunostaining progressively with the decrease in cell differentiation. Statistical analysis indicated the predominance of high FSS in the ISUP 4-5 groups and low FSS in the ISUP 1-2 groups, aspects that were statistically significant. Ezrin was expressed in the majority of PAs analyzed and its expression was associated with ISUP grades, an aspect that suggests involvement in PA progression.

Classification and Grading Systems in Gastric Adenocarcinomas.

Gastric adenocarcinomas are lesions that raise important issues in clinical practice, due to their incidence and biological behavior. Over time, various systems have been used for classifying and grading of gastric adenocarcinomas, in the hope of increasing the diagnostic accuracy. In this study we statistically analyzed 112 cases of gastric adenocarcinomas in relation to different classification and grading systems, in order to identify their efficacy and concordance in the histopathological diagnosis. The results indicated a significant association of the Lauren and World Health Organization 2019 classifications and also between these and the three-tier and two-tier grading systems, which supports their practical utility in establishing the diagnosis and assessment of the tumor aggressiveness, for the differentiated therapy.

Non-Melanoma Skin Cancer: Statistical Associations between Clinical Parameters.

Non-melanoma skin cancer (NMSC) represent an important health problem in medical practice. This is the most frequent type of cancer and its incidence is constantly increasing. Basal cell carcinoma and squamous cell carcinoma constitute the majority of NMSC, respectively 70% and 25% of total cases. The present retrospective study was conducted over a one-year period and included 439 cases of NMSC, of which 336 BCC and 103 SCC. We analyzed a series of clinical parameters: gender, age, tumor size and tumor topography. The statistical analysis of the investigated parameters indicated gender-age associations for BCC, and topography-gender, as well as topography-age for SCC.

Histopathological Study of the Prostate Cancer Growth Patterns in Relation with the Grading Systems.

Prostate adenocarcinomas are common lesions with a high incidence and variable prognosis, which can be assessed using tumor grading systems. In this study, we analyzed 329 prostate adenocarcinomas in relation to tumor variants, growth patterns, classical and updated grading systems. The study indicated statistical associations of atrophic, pseudohyperplastic and microcystic variants with low grading scores, the associations of glomeruloid, cribriform with or without necrosis and signet ring-like cell variants with high grading scores, and also of single growth patterns with intermediate scores, which supports the accordance and usefulness of existing grading systems for the identification of aggressive prostate tumor lesions.

The role of cell adhesion molecules in the progression of bladder urothelial carcinomas.

Alteration of the intercellular adhesion system plays an essential role in the initiation and progression of bladder carcinomas. We followed the immunoexpression of adhesion molecules, E-cadherin, ß-catenin and Claudin-1, in relation to the histopathological grade and the pT category in a number of 50 urothelial carcinomas of the bladder, based on a final staining score (FSS), calculated on the basis of reaction intensity and labeled cells number. E-cadherin immunoexpression was identified in the membrane of tumor cells, low FSS being associated with invasive high-grade carcinomas. ß-catenin reactions were membranous in the case of low-grade noninvasive carcinomas and predominantly cytoplasmic and nuclear in the case of high-grade invasive ones, for which high FSS were associated. Claudin-1 was identified at the membrane level, the high FSS values being more frequent in the case of high-grade invasive carcinomas, although there were no significant statistical associations. Loss of E-cadherin expression and the associated positive linear relation of ß-catenin and Claudin-1 indicate the usefulness of the analyzed markers in identifying the invasive aggressive phenotype of urothelial bladder carcinomas.

Locally advanced choroidal melanoma with favorable molecular prognosis - case report.

Uveal malignant melanoma is a rare malignant tumor comprising less than 5% of melanoma cases. It is nevertheless the intraocular tumor with the highest incidence in adults, that arises from the melanocytes in the uveal tract. The authors present the case of a patient with locally advanced choroidal melanoma: from presentation to diagnosis, treatment, and prognosis. A 63-year-old female patient presented in the Ambulatory of the Emergency County Hospital, Craiova, Romania, on the February 1, 2021, accusing visual acuity drop and photophobia in her left eye for about three weeks. Pathology examination in Hematoxylin-Eosin (HE) staining reveals a dense cell proliferation, with small and medium spindle cells and pigment production. The following immunohistochemical markers were used in our study: human melanoma black 45 (HMB45), Ki67, cyclin D1, B-cell lymphoma 2 (Bcl2), S100, Wilms' tumor 1 (WT1), p16, and p53. Uveal melanoma is a malignant tumor that can arise in all the uveal components: iris, ciliary body, and choroid. Out of the three components, iris melanomas have the best prognosis, while ciliary body melanomas have the worst prognosis. It is mandatory for the patient to respect the follow-up schedule, as follow-ups can provide early diagnosis of eventual metastasis.

Immunoexpression of E-cadherin, CD44 and Claudin 7 in gastric adenocarcinomas.

Gastric adenocarcinomas represent frequent malignant tumors in the digestive tract, with a high and constant mortality rate in last decades. The disturbance of the adhesion molecules expression, which normally is essential in maintaining epithelial homeostasis, has a critical role in the initiation and progression of tumors. In this study, we analyzed the immunoexpression of E-cadherin, cluster of differentiation 44 (CD44), and Claudin 7 in 58 cases of gastric adenocarcinomas, in relation to the histopathological parameters of the lesions' aggressiveness. Increased E-cadherin immunoexpression was observed in tubular adenocarcinomas, those of low grade and in stages I-III. CD44 presented high scores in discohesive, hepatoid, tubular, and tubulopapillary adenocarcinomas, those of high grade and in advanced stages. Claudin 7 associated increased scores for tubular, tubulopapillary and micropapillary tumors, those of low grade and mainly in stage I. The markers used in the study can be useful for assessing the aggressiveness of gastric adenocarcinomas, in the context of specific adapted therapy.

VEGF Immunoexpression in Prostate Adenocarcinoma.

Angiogenesis is a basic biomolecular mechanism for tumor progression, the vascular endothelial growth factor (VEGF) being one of the main enhancers of this complex process. In this study, we analyzed VEGF-A immunoexpression in 61 prostate adenocarcinomas (PAs), related to the prognostic parameters of the lesions. VEGF scores were higher in PAs that associated serum PSA values above 20ng/ml, in tumors with pure complex or mixed growth patterns, as well as in high-grade and advanced lesions. The results obtained indicate the involvement of VEGF in prostate angiogenesis and the usefulness of the maker for the identification of aggressive lesions.

Cerebrolysin Prevents Brain Injury in a Mouse Model of Liver Damage.

Liver damage can lead to secondary organ damage by toxic substances and catabolic products accumulation which can increase the permeability of blood-brain barrier, leading to cognitive impairment. The only real treatment for end stage liver failure is grafting. With some, but not all, neurological symptoms subsiding after transplantation, the presence of brain damage can impair both the short and long-term outcome. We tested if Cerebrolysin can prevent brain injury in an experimental model of non-viral liver damage in mice. Behavior, abdominal ultrasound evaluation and immunohistochemistry were used to evaluate the animals. No ultrasound or behavior differences were found between the control and treated animals, with both groups displaying more anxiety and no short-term memory benefit compared to sham mice. Cerebrolysin treatment was able to maintain a normal level of cortical NeuN+ cells and induced an increase in the area occupied by BrdU+ cells. Surprisingly, no difference was observed when investigating Iba1+ cells. With neurological complications of end-stage liver disease impacting the rehabilitation of patients receiving liver grafts, a neuroprotective treatment of patients on the waiting lists might improve their rehabilitation outcome by ensuring a minimal cerebral damage.

Clinicopathological Correlations in Cutaneous Squamous Cell Carcinomas.

Squamous cell carcinomas (SCC) represent 20% of all nonmelanoma skin cancers, most tumors responding favorably to the conventional therapy. Incisional or excisional biopsy is essential for diagnosis and prognosis evaluation. The study included 103 cases of SCC, following the assessment of some clinical and histopathological aggressivity factors, which were digitally stored and statistically analyzed using comparison tests. The tumor grade was significantly associated with the histological variant, the maximum tumor size, the perineural and lymphovascular invasion, the depth of the invasion and the status of resection limits. The pT category was significantly associated with the location and maximum tumor size, perineural invasion, depth of invasion and status of resection limits. It was observed a significant association of tumor grade and pT category. The evaluation of the clinical and histological characteristics of SCC is an important step in obtaining relevant prognostic information and applying appropriate therapy.

E-cadherin, fibronectin and Slug immunoexpression in non-melanoma skin cancers.

Epithelial-mesenchymal transition (EMT) is an essential biological process involved in the initiation and progression of cancer by which epithelial tumor cells lose their differentiated characteristics, such as cell-cell adhesion and apical-basal polarity and acquire a more invasive and∕or metastatic mesenchymal phenotype. The present study investigated the expression of immunomarkers with a role in EMT of non-melanoma skin cancers (NMSCs), such as E-cadherin, fibronectin and Slug, for a number of 50 NMSCs, represented by 30 cases of basal cell carcinomas (BCCs) and 20 cases of squamous cell carcinomas (SCCs). For BCC, the statistical analysis of the investigated immunomarkers indicated significantly differences in relation to the depth of invasion, and for E-cadherin and fibronectin with the degree of risk. In the case of SCC, the statistical analysis indicated significant differences of E-cadherin and Slug with the degree of tumor differentiation, and for fibronectin and Slug with the depth of invasion. The analysis of the distribution for the percentage values of the investigated immunomarkers in the case of BCC indicated a significant negative linear relation between E-cadherin/fibronectin and E-cadherin/Slug, and in SCC a significant negative linear relation between E-cadherin∕fibronectin, E-cadherin∕Slug and a positive linear one in the case of fibronectin∕Slug. The study indicates through the statistically significant relation between E-cadherin∕fibronectin and E-cadherin∕Slug, the EMT intervention in carcinogenesis of NMSC.

Immunoexpression of Ki67, p53 and cyclin D1 in osteosarcomas.

The main malignant tumor of the bone tissue is represented by osteosarcoma, neoplasia with a reserved prognosis and an unpredictable evolution, often aggressive. Cell cycle disruption is one of the complex biomolecular mechanisms involved in the progression of osteosarcomas. In this study, we analyzed the immunoexpression of Ki67, p53 and cyclin D1 for 18 primitive osteosarcomas in relation to the clinicopathological prognosis parameters of the lesions. The results indicated the predominance of lesions in male young patients, with femoral location, most tumors being represented by the osteoblastic type, with high grade, size <8 cm and in advanced stages. Reactions were present in all cases, the high immunoexpression being associated with osteoblastic∕epithelioid types (Ki67, cyclin D1, p53), high grade (Ki67, cyclin D1) and advanced stage (Ki67, cyclin D1). The study revealed a positive linear relation of the investigated immunomarkers expression, which indicates their usefulness in identifying lesions with aggressive progression potential.

Virtual autopsy and confirmation of normal fetal heart anatomy in the first trimester using three-dimensional (3D) reconstruction of histological sections.

OBJECTIVE: In this pilot study, we tested the feasibility of cardiac structures reconstruction from histological sections in 12-13 weeks normal fetuses. Conventional autopsy is hampered at this gestational age because of the small size of the heart anatomical structures, while alternative non-invasive methods for pathology examination of the fetus are expensive, rarely available and lack accuracy data regarding the confirmation of first trimester heart defects suspected by early prenatal ultrasound (US) scans. MATERIALS AND METHODS: Normal hearts from fetuses aged 12-13 gestational weeks (GW) were harvested for histological preparation, virtual reconstruction, and cardiac structures analysis. The normalcy of heart structures was confirmed before pregnancy termination, using a detailed US scan protocol. The fetal heart was routinely processed for formalin fixation and paraffin embedding (FFPE) and 10 µm seriate sections have been cut until finishing the specimen. All sections have been scanned and a three-dimensional (3D) reconstruction of the whole organ has been rendered, based on computer-aided manual tracing. Using the 3D navigation software, the main cardiac structures were searched for a proper and confident visualization. RESULTS: Five cases were investigated. Visualization of the normal heart cavities, including atrioventricular septum was very good in all fetuses. The entire course of right and left ventricle outflow tracts was confidently confirmed, along the branching pattern of aorta and pulmonary artery trunk. Regarding the veno-atrial connections, it was easy to identify the entrance of the inferior and superior caval veins into the right atrium, but a detailed review of the histological sections was necessary for the visualization of the left atrium venous openings. The inherent morphological deformation following heart block sectioning resulted in a lower resolution or quality of the "reconstructed" planes, but these distortions did not represent a significant impediment in any of the cases. The resources involved ordinary histology and information technology (IT) equipment. To further decrease the time involved by the protocol, many steps may be automated: cutting, coloring, and scanning. CONCLUSIONS: The results indicate that this method can be implemented to routine clinical practice. The use of 3D reconstruction of fetal heart histological sections in first trimester may serve as an important audit to confirm the normalcy of heart structures. Also, the histological and postprocessed information is retained, and this volume can be stored, reanalyzed, or sent online for a second opinion. The method involves relatively undemanding resources, i.e., hardware, software, competences, and time. The procedure could also benefit from refinements used in other imaging techniques to limit human-computer interactions, such as sections distortion.

Analysis of Prostate Adenocarcinoma Histopathological Types in Relation to Tumor Grade.

Prostate adenocarcinomas are some of the most common malignancies diagnosed in men, and the evaluation of tumor growth patterns is the basis for establishing the aggressiveness of the lesions. The study included 283 cases of prostate adenocarcinomas for which histopathological type and tumor grade were analyzed. The results indicated the association of ductal, sarcomatoid and signet ring-like cell types with aggressive growth patterns and high scores, atrophic and pseudohyperplastic types with mild growth patterns and low scores, foamy gland type presented intermediate growth patterns/scores, while conventional and colloid types had variable aspects. The grading systems used may be considered consistent with the histological types of prostate adenocarcinomas.

The immunoexpression of MMP-1 and MMP-13 in eyelid basal cell carcinoma.

Basal cell carcinoma (BCC) is the most frequent human malignancy and at the same time the most frequent periocular malignancy, representing almost 80% of all non-melanoma skin cancers and 90% of eyelid cancers. The study included 50 cases of eyelid BCC, out of which 41 were nodular BCC (NBCC) and nine were infiltrative BCC (IBCC), with various Breslow scores (BS) and primary tumor (pT) category. We analyzed the immunoexpression of matrix metalloproteinases (MMPs) 1 and 13 in the tumoral epithelial component (TEC) and inflammatory stromal component (ISC) of BCC in relation to the two histopathological parameters. The immunoreaction for MMP-1 was identified in 41 (82%) cases and for MMP-13 in 46 (92%) cases both in the TEC and ISC of both types of BCC. The statistical analysis revealed that both collagenases had positive/high scores significantly associated with advanced BS. For MMP-1, there were statistical associations in TEC related to IBCC and high pT category, while MMP-13 only revealed statistical association in ISC with high pT. The presence of collagenase MMP-1 and MMP-13 expression in a high number of cases, both in TEC and ISC, confirms their intervention in the tumor progression and proposes these MMPs as potential targets in antineoplastic therapy.