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Background: Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature are inconsistent. Material and Methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, which was not previously reported but is a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, an analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Monitoring disease activity in inflammatory bowel disease (IBD) is challenging since clinical manifestations do not represent reliable surrogates for an accurate reflection of the inflammatory burden. Endoscopic remission had been the most significant endpoint target in the last years; nevertheless, a remarkable proportion of patients continue to relapse despite a normal-appearing mucosa, highlighting that endoscopy may underestimate the true extent of the disease. A subtle hint of the importance that histology plays in the long-term course of the disease has been endorsed by the STRIDE-II consensus, which recommends considering histologic healing for ulcerative colitis (UC), even though it is not stated to be a compulsory formal target. It is a continuum-changing paradigm, and it is almost a certainty that in the near future, histologic healing may become the new formal target for ulcerative colitis. It must be emphasized that there is great heterogeneity in defining histological remission, and the main criteria or cut-off values for inflammatory markers are still in an ill-defined area. The complexity of some histologic scores is a source of confusion among clinicians and pathologists, leading to low adherence in clinical practice when it comes to a homogenous histopathological report. Therefore, a standardized and more practical approach is urgently needed.

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.

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., Competing Interests: None to declare., (Copyright © 2023, Medical University Publishing House Craiova.)

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., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022, Medical University Publishing House Craiova.)

Disturbance of the intercellular adhesion system represents a basic biomolecular mechanism in gastric carcinogenesis. Claudin 4 is member of a protein family involved in maintaining homeostasis and epithelial integrity. In this study, we analyzed the immunoexpression of Claudin 4 in 58 cases of gastric adenocarcinomas, in relation to the main histopathological parameters of aggressiveness, the reactions obtained being evaluated through the intensity of the reactions and the number of positive cells. Positive membranous reactions of Claudin 4 were observed in all cases, in tumor cells and some stromal elements, but in some high grade gastric adenocarcinomas also cytoplasmic immunostaining was present. Claudin 4 high scores were associated with tubular, tubulopapillary and hepatoid adenocarcinomas, of low grade and in early stages, aspects that suggest the usefulness of the marker in evaluating the aggressiveness of gastric epithelial tumors., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022, Medical University Publishing House Craiova.)

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., Competing Interests: None to declare, (Copyright © 2022, Medical University Publishing House Craiova.)

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.

Endometrioid endometrial carcinomas (EEC) are common malignant lesions of the female genital tract, with incidence and risk factors that raise issues to improve histopathological prognostic factors. The study included 50 EEC cases, for which the clinicopathological parameters represented by age, risk factors, tumor grade, histological differences, invasion pattern, tumor stage and association of endometrial hyperplasia were analyzed statistically. The results indicated the predominance of EEC in the 7th decade of life, with associated risk factors (78%), more frequently well differentiated (52%), with no other specifications related to differentiation (NOS, 60%), with irregular invasion pattern (66%) in<50% of the myometrial wall (48%). Irregular pattern, microcystic, elongated, and fragmented (MELF) pattern and myoinvasion associated with vascular invasion (MVI) pattern were significantly associated with high grade and advanced stage tumors. With the exception of EEC-NOS and squamous differentiation, all other tumors were associated with low grade (G1). In this study there was a tendency to associate the age group of 60-69 years with the presence of endometrial hyperplasia and with high grade and advanced stage. Apart from the high grade and advanced stage, in the aggressive profile of the EEC can be included as the clinicopathological parameters the 7th decade of life and the irregular, MELF and MVI invasion patterns., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

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., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

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., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

Endometrioid endometrial carcinomas (EECs) are the most common malignancies of the uterus. Hormonal dependence of EEC, in relation to biomolecular mechanisms involved in tumor progression, such as angiogenesis and cell proliferation, are aspects that can contribute to improving the prognosis of patients. We analyzed the immunoexpression of markers addressed to steroid hormone receptors [estrogen receptor (ER), progesterone receptor (PR)], angiogenesis [cluster of differentiation (CD)105∕endoglin] and cell proliferation (Ki-67) in 50 EECs related to the histopathological prognostic criteria of the lesions. In this study, the ER and PR scores were higher in low grade and early stages EEC, the statistical aspects being variable. The CD105 microvessel density and the Ki-67 proliferation index were superior in high grade and advanced stages EEC, the statistical aspects being significant or at the limit of significance. The ER∕PR and CD105∕Ki-67 immunomarker groups indicated a positive linear intragroup relation and a negative linear intergroup relation, suggesting the presence of synergistic and antagonistic molecular mechanisms of tumor endometrial control that can be used to stratify patients for targeted therapy.

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, β-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. β-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 β-catenin and Claudin-1 indicate the usefulness of the analyzed markers in identifying the invasive aggressive phenotype of urothelial bladder carcinomas.

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., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

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.

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.

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., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

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., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

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., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

The involvement of claudins in urothelial carcinogenesis is controversial. In this study, we analyzed Claudin-4 immunoexpression in 50 cases of bladder urothelial carcinomas depending on the main prognostic parameters of the lesions represented by the tumor grade and tumor extension. Claudin-4 immunoexpression scores were significantly higher in high-grade urothelial carcinomas and in tumors with invasion in muscularis propria. The results obtained indicate the involvement of Claudin-4 in the progression of urothelial bladder carcinomas., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

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.

Chronic palatal and nasopharyngeal inflammations are common lesions in pediatric pathology, with major effects on children's development. The study included 34 cases of chronic tonsillitis and adenoiditis for which we quantified immunohistochemically and analyzed the distribution of inflammatory elements in the follicular, extrafollicular and epithelial compartments, in relation to the composite histological scores and the clinico-epidemiological profile of the lesions. The cases were more frequent under the age of 10, in female patients, coming from urban areas, with the diagnosis of tonsillitis. B-lymphocytes have been associated with follicular areas in tonsillitis and epithelial areas in adenoiditis. In all compartments, T-lymphocytes were more frequently associated with tonsillitis and plasma cells associated with adenoiditis. Macrophages and dendritic cells had a relatively uniform distribution for the three compartments in all cases. The results obtained indicate different inflammatory phenotypes for chronic tonsillitis and adenoiditis, an aspect that may be useful for stratifying patients for optimal therapy.

Prostate adenocarcinoma (PA) is by incidence and prognosis a unique model for investigating the biomolecular mechanisms involved in tumor progression. In this study, we analyzed the immunoexpression of androgen receptor (AR), cluster of differentiation 105 (CD105) and Ki67 for 61 cases of PA, in relation to the main clinicopathological parameters of the lesions. The AR scores, CD105 microvessel density (MVD) and Ki67 proliferation index (PI) were significantly higher in patients with serum prostate-specific antigen (PSA) above 20 ng∕mL, in ductal, colloid and sarcomatoid types of PA, in growth patterns 4-5 or mixed, respectively in the case of high-grade advanced stage tumors, with perineural and vascular invasion, as well as in groups with a reserved prognosis. The results obtained, reflected in the positive linear correlation of AR, CD105 and Ki67 expression, indicate synchronous endocrine, angiogenic and proliferative mechanisms involved in tumor progression, which can be used to optimize the targeted tumor therapy.

Atypical meningiomas with a mixed glial-epithelial phenotype are rare reports, and here we described an aggressive case on which double immunofluorescence ascertained the co-expression of epithelial membrane antigen (EMA) with glial fibrillary acidic protein (GFAP) in the same tumor cells. A 62-year-old female presented with acute intracranial hypertension symptoms occurred over the last 24 hours, muscle weakness on the right side, cerebellar dysarthria, and wide base gate. Magnetic resonance imaging (MRI) examination showed a right cerebellar hemisphere non-homogenous tumor, with intense gadophylia, diffuse contours, and necrotic inner areas. There were also scar-like areas at the level of the left cerebellar hemisphere, and the patient recalled a previous surgical intervention at the age of 6 years old without further diagnostic data. The patient suffered an ischemic event in the brain stem and died shortly after the surgical removal of the tumor. Histopathology revealed an epithelial-like tumor with moderately pleomorphic and elongated cells arranged in fascicles, rare necrotic areas, and a few proliferating multilayered vessels structures. Immunohistochemistry (IHC) revealed variable EMA positivity, intense vimentin staining, rare GFAP-positive intra-tumor areas, a moderate expression for cytokeratin 8/18, reduced labeling for an anti-progesterone receptor (PrgR) antibody, cluster of differentiation (CD) 10 negativity, and a high Ki-67 proliferating index of around 40%. The case was deemed as an atypical meningioma, and interestingly, a double IHC for GFAP∕EMA revealed a strong colocalization of the two markers in the tumor mass. Although extremely rare, the reports of meningiomas expressing a mixed epithelial∕glial profile might be connected with their aggressive evolution. Double IHC might help in predicting the evolution of these cases and determine which patients should benefit from closer surveillance.

Through the increasing incidence and association of asthma, chronic rhinitis (CR) raises major problems in the pathology of children and adolescents. The evaluation of the inflammatory status together with the diagnosis and the tandem treatment of the two conditions can contribute to the improvement of the patients' quality of life. In this study, we analyzed the immunoexpression of cluster of differentiation (CD) 20, CD8, CD138 and eosinophil major basic protein (MBP) in 24 cases of CR in adolescents, in eight of them existing the association of asthma. Symptoms of CR and allergic status, as well as histopathological changes specific to a persistent inflammation, were identified in this study. The CD20∕CD8 immunophenotype was more specific for CR, while the CD138∕eosinophil MBP immunophenotype was specific for asthma-associated chronic rhinitis (AACR). The negative linear distribution of lymphocyte elements compared to plasmocytes and eosinophils specific for the allergic status can support the protective effect of CD8 T-lymphocytes and the presence of a semi-activated B-lymphocyte status in CR. The results may be useful for improving the stratification criteria of patients for therapy.

Clear cell renal cell carcinomas (ccRCC) represent about 80% of the malignant neoplasia with this localization. Snail, Twist1 and Slug are transcription factors and play a central role in the epithelial-mesenchymal transition (EMT), which is involved in the progression of renal cell carcinoma (RCC). In this study, we analyzed the immunoexpression of these transcription factors in 50 cases of ccRCC, in relation to histopathological aggressiveness parameters of the lesions. The results indicated the association of Snail and Twist1 expression with high Fuhrman grade, as well as the association of Slug expression with low Fuhrman grade. The immunoexpression of Snail and Twist1 was significantly superior for advanced stages and Slug was overexpressed in early stages of ccRCC. Our study supports the usefulness of the Snail, Twist1 and Slug expression for the appreciation of aggressiveness in ccRCC, the panel being attractive for targeted therapy.

One of the mechanisms involved in gastric carcinomas progression is represented by epithelial-mesenchymal transition (EMT), a complex process during which tumor cells acquire an invasive and migratory mesenchymal phenotype. In this study, we analyzed the immunoexpression of E-cadherin, P-cadherin and fibronectin in 50 gastric carcinomas, in relation with the tumoral type, differentiation grade and lesions stage. The reactions presented variable patterns related to lesions stage. Membrane and cytoplasmic reactions were present in 62% of cases for E-cadherin and in 56% of cases for P-cadherin, being present only cytoplasmic in 34% of cases for fibronectin. The immunoexpression for E-cadherin and P-cadherin was superior in tubular gastric carcinomas, of low grade and early stage, while fibronectin expression was superior in discohesive or mixed gastric carcinomas, of high grade and in advanced stages. Negative E-∕P-cadherin and positive fibronectin immunophenotype may be associated with aggressive gastric carcinomas and supports the EMT involvement in gastric carcinogenesis.

Alteration of cadherin immunophenotype is associated with the epithelial-mesenchymal transition, a complex biomolecular mechanism involved in carcinomas progression. The study investigated the immunoexpression of E-, P- and N-cadherins in 50 serous malignant tumors of ovary related to the histopathological prognostic parameters of the lesions, using a quantification based on scores that took into account the number of marked cells and the intensity of the reactions. The E-cadherin and P-cadherin immunostainings were significantly superior in serous borderline tumors (SBTs) compared to carcinomas, as well as in advanced carcinomas compared to early stages. Although the immunoreactions indicated higher scores in high-grade serous carcinomas (HGSCs) versus low-grade ones (LGSCs), the aspect was without statistical significance. Immunoreactions of N-cadherin were present only in HGSC, being significantly superior in the advanced stages of tumors. Ovarian serous malignant tumors expressed E-, P- and N-cadherins in different proportions, the altered cadherin phenotype being associated with progression of the disease. The results can be used to identify tumors with progression potential and to better stratify patients for specific therapy.

Alteration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expression has been studied for various cardiac diseases, including dilated cardiomyopathy (DCM), with the significance of surrogate markers of extracellular matrix (ECM) remodeling. In this study, we determined the MMP-8, MMP-9 and TIMP-2 immunoexpression in the heart of patients diagnosed with DCM in relation to a histological composite score (HCS). The study included 40 cases of heart fragments that were processed by the usual paraffin inclusion technique, followed by a semi-quantitative evaluation of histopathological parameters, which summed, allowed the establishment of a HCS. Subsequently, the cases were immunohistochemically processed for MMP-8, MMP-9 and TIMP-2, followed by the semi-quantitative evaluation of their expression intensity. MMP-8 was identified only in myocardiocytes, while MMP-9 and TIMP-2 were present in both myocardiocytes and stroma, but with different intensity. The increasing intensity of MMP-8 and TIMP-2 immunoreactions was significantly associated with low HCS. In case of MMP-9, the immunostaining intensity analysis in relation to the HCS level revealed insignificant differences, but we found an association of increased and moderate intensity with low HCS. The imbalance between TIMPs and MMPs disrupts the ECM architecture and contributes to the remodeling process in DCM, aspect that can be used in the development of new clinical therapies.

Benign serous ovarian epithelial tumors represent a major area of interest in pediatric pathology through the incidence and the hormonal and reproductive implications that they induce. In this study, we analyzed 24 tumors diagnosed and surgically operated in children and adolescents, in relation to clinical, histological and immunohistochemical parameters, which can provide information on the potential for growth of lesions. The average age of diagnosis was 13.2 years, the majority of tumors being present in patients over 10 years (75%), with accompanying symptoms (83.3%), unilateral (91.7%) and dimensions of maximum 10 cm (66.7%). The histopathological aspect indicated a cystic growth pattern, sometimes papillary, and in three cases, the presence of atypical focal areas of the tumor epithelium. The Ki67 proliferation index values were higher in the case of tumors larger than 10 cm, those with papillary pattern, and in those with atypical areas, while p53 reactions were present only in cases with atypical proliferation areas. The parameters investigated in this study are useful both for assessing the risk of tumor growth and progression, as well as for stratifying patients for active clinical surveillance.

Dilated cardiomyopathy is the most common form of cardiac muscle disease, accounting for approximately 60% of all cardiomyopathies. We proposed to identify histopathological changes of the myocardium in dilative cardiomyopathy. This study comprised a total of 19 cases, represented by myocardial fragments from deceased patients with diagnosis of dilated cardiomyopathy. Histopathological analysis allowed changes to be observed for both myocytes and myocardial interstitial components. We have found a combination of hypertrophic, atrophic and normal myocardocytes, or associated with the presence of hydropic changes. We rarely identified the aspect of myocytosis, cytoplasmic accumulation of lipofuscin pigment or mucinous material, and variable nuclear pleomorphism. At the interstitial level we noticed changes in fibrosis, lipomatosis and rarely the presence of inflammatory infiltrate. Histopathological characteristics of the myocardium in dilated cardiomyopathy are numerous but nonspecific, similar to those in the terminal stages of other cardiac diseases.

Clear cell renal cell carcinoma (CCRCC) are the most frequent type of renal cell carcinoma. Fuhrman grade and tumor stage are prognostic factors with great importance in survival rate. This study was performed on 75 cases of CCRCC diagnosed by the Anatomical Pathology Laboratory of the County Clinical Emergency Hospital of Craiova between 2014 and 2017. The biological material was represented by pieces of nephrectomy. The cases were analyzed on two criteria: epidemiology (age, sex) and histopathology (Fuhrman grade, tumor stage, architectural pattern, sarcomatoid transformation, and necrosis). Statistical analysis was done using Chi Square tests in IBM SPSS software. Average diagnosis age of CCRCC was 58.8±10.2 years, predominantly in male patients (66.7%). Tumor sizes were between 2 and 14cm, with an average of 6.7±2.9cm. Most cases were determined to be tumor stage III (60%) and Fuhrman grade 2 (56%), followed, in order of frequency, by tumor stages I and II (28% and 10.7%) and Fuhrman grades 3 and 1 (21.3% and 20%). High Fuhrman grade CCRCC were significantly associated with advanced tumor stage (p<0.05, χ 2 test). Most cases presented a mixed pattern, significantly associated with advanced tumor stages (p<0.05, χ 2 test). Even though the presence of sarcomatoid transformation was more frequent in advanced tumor stages, it wasn't significantly linked to them (p<0.05, χ 2 test). Conclusions: Analyzed histopathological parameters are useful for determining CCRCC aggressiveness. CCRCC in advanced tumor stages is associated with high Fuhrman grade and mixed architectural pattern.

Micropapillary carcinoma was recently identified as a carcinoma variant characterized by the presence of small clusters of tumor cells located in optically empty spaces. The study included a number of 14 cases represented by surgical excision specimens diagnosed with gastric carcinoma (tubular, papillary and signet-ring) which associated the micropapillary component in variable proportions. Regarding the low-grade tubular carcinomas, the micropapillary component represented less than 25% of the tumor, while in the high-grade tubular carcinomas and papillary carcinomas it represented 25-50%. Among signet-ring carcinomas, the micropapillary component had a percentage of over 50. The depth of invasion was frequently associated with T3 and T4 categories. Lymph nodes metastasis were found in ten cases and distant metastasis were present in three cases. Recognition of the micropapillary component associated with gastric carcinoma represents an aspect of great importance because it is frequently correlated with unfavorable prognosis parameters.

The majority of colorectal carcinomas are adenocarcinomas derived from the colic mucosae cell, more frequently moderately differentiated. The purpose of this study was to determine de incidence of CRC and the relationship between histopathological risk factors in patients with colic adenocarcinomas. The study included 144 cases of CRC diagnosed within the Pathology Laboratory of the Clinical County Hospital of Craiova in the year 2017.The biological material consisted in samples from colectomies and hemicolectomies provided from patients admitted within the surgical clinics of the same hospital, then fixed with 10% buffered formalin and afterwards processed using the classic histopathological technique of paraffin inclusion and staining with hematoxylin and eosin. We observed certain histopathological parameters such as: pattern, grading, stage, vascular invasion and neural invasion. The mean age of diagnostic was 68.6 ± 11.2, and it was predominantly male patients (64.6%). Most cases presented with mucinous pattern (31.9%) and cribriform comedocarcinoma type (29.9%). The majority were classified as stage III B (34%), being moderately differentiated (64.6%) and associated with vascular invasion (47.2%) and perineural invasion (25.7%). Statistical analysis indicated significant relationships between tumor stage and differentiation grade (p<0.01, χ²test), as well as between tumor stage and vascular invasion (p<0.05, χ²test), without including perineural invasion (p<0.05, χ²test).

Basal cell carcinomas (BCCs) are malignant tumors with particular biological prognosis and behavior, and the biomolecular investigation of these lesions can provide important therapeutic targets for epithelial neoplasia. In this study we analyzed the immunoexpression of transforming growth factor beta 3 (TGFβ3) and its receptor type III (TGFβRIII) for 53 cases of BCC in relation to the main histopathological prognostic parameters. The results indicated statistically significant differences of TGFβ3 and TGFβRIII expression related to histological type and lesion stage, the both proteins being higher expressed in adenoid and morpheaform advanced stage tumors. In this study, TGFβ3 and TGFβRIII immunoexpression analysis indicated their utility for identifying aggressive BCCs with potential for tumor progression.

The epithelial growth factor receptor (EGFR) is involved in various stages of cancer growth such as tumor initiation, angiogenesis and metastasis, being an attractive target for oncogenic therapy. The present study aims to evaluate the EGFR expression in 54 cases of serous and mucinous ovarian borderline tumors and carcinomas. EGFR expression was present in more than half of the investigated tumors, more frequently in carcinomas than in borderline tumors, especially in the serous type. The highest values of the final staining score (FSS) were observed only in serous carcinomas in the advanced stages of the disease. As a result of frequent expression of EGFR in ovarian tumors, it is necessary to monitor EGFR inhibitors for ovarian cancer therapy, but probably after establishing more rigorous selection and stratification criteria for patients.

Clear cell renal cell carcinomas (CCRCCs) are the most common kidney tumors that despite current advances in diagnosis continue to have high rates of metastasis and mortality. In this study, we analyzed the cytokeratin (CK) AE1∕AE3 and vimentin immunoexpression in 26 CCRCCs in relation to histopathological prognostic parameters. Immunoreactions were positive and heterogeneous in all analyzed cases. CK AE1∕AE3 immunoexpression was associated with low grade and early stage lesions, while vimentin immunoexpression was associated with high grade and advanced lesions. The aspect may be used to determine the tumor heterogeneity and a better patients' stratification for therapy.

Endometrial cancer is one of the most common tumors in women worldwide. P53 has a well-known function as tumor suppressor, but it can also regulate the tissues metabolism, differentiation and development. Snail is a zinc-finger transcription factor, involved in the cell differentiation and survival. We analyzed the immunoexpression of p53 and Snail in 55 cases of endometrioid endometrial carcinoma (EEC), in relation with the histopathological prognosis parameters and tumoral compartments, respectively intratumoral and advancing edge areas. For both markers, we found a statistically significant association with histological grade, in relation with tumoral compartments. P53 and Snail can be used in developing EEC targeted treatment.

Basal cell carcinoma (BCC) is a variety of cutaneous carcinoma associated with an excellent prognosis because it rarely metastasizes, but it can cause significant local destruction and morbidity if surgical excision is not made. In this study, we examined the immunohistochemical expression of p53 and cyclooxygenase-2 (COX-2) in 51 BCCs, nodular and infiltrative subtypes, with various Clark levels. The immunoexpression of p53 was identified in 74.5% BCC cases and COX-2 reactions in 88.2% of cases. The scores of p53 reactions revealed significant differences depending on Clark level and borderline significance with tumor type, the high positive scores being associated to infiltrative tumors and high Clark level. No differences were revealed between COX-2 scores with both Clark level and tumor type. The analysis of the percentage values of p53 and COX-2 indicated a positive linear correlation. The positivity of p53 and COX-2 in a large proportion of BCCs, regardless of histological type and of depth of invasion, supports the two markers involvement in tumor progression.

Complex and modern obstetric medical care provides a constant improvement for the pregnancy prognosis. Thus, young women with an undiagnosed pathology become pregnant and, during pregnancy, the previously undiagnosed pathology, without any clinical signs and symptoms, becomes present during pregnancy, having an unfavorable impact on the fetus and the health state of the pregnant woman. The gestational syndromes during pregnancy influence the woman's health state over a long period of time and the quality of the conception product. The recommendation, performance of laboratory tests and imagistic investigations at the right time during pregnancy, as well as a correct interpretation of their results, may prevent the onset of catastrophic occurrences including fetal death in utero and/ or maternal death. We report the case of a 30-year old primigesta, primipara (IGIP) patient with a singleton, naturally obtained pregnancy, severe preeclampsia, severe IUGR and thrombophilia.

Basal cell carcinomas (BCCs) are the most common malignant skin tumors, with variable prognosis and recurrence rates, depending on histopathological subtypes. The study analyzed the immunoexpression of epidermal growth factor receptors (EGFRs) in 53 cases of nodular, adenoid and morpheaform BCCs in relation to clinico-pathological associated parameters. We found significant differences in the expression of EGFR, HER2 and HER3 reported to histological BCC types. The nodular type presented the weakest expression of EGFRs, while the morpheaform type had a high expression of all receptors and the adenoid type an increased expression only in case of EGFR and HER2. This study supports the involvement of EGFR, HER2 and HER3 in BCC aggressiveness of and in tumor differentiating towards different histological subtypes.

Stromal microinvasion in ovarian serous borderline tumors can take various aspects, some of which are difficult to identify. Thus, the identification of stromal microinvasion is relatively simple for typical intracystic papillary proliferations such as serous borderline tumors, but may be difficult for tumors with glandular component. The study analyzed 14 cases of ovarian serous borderline tumors diagnosed in patients with mean age of 47,1 years. Histopathologically all tumors corresponded to typical forms in which we identified only two cases of stromal microinvasion. In one case, microinvasion was of eosinophilic type, and in the other case was observed a glandular and micropapillary pattern, being associated with the noninvasive peritoneal implants.