Publications by authors named "Mariana Aschie"

34 Publications

Surfactant proteins analysis in perinatal deceased preterm twins among the Romanian population.

Medicine (Baltimore) 2022 Jul 29;101(30):e29701. Epub 2022 Jul 29.

Medicine Faculty, "Ovidius" University of Constanta, Constanta, Romania.

The molecular basis of the evaluation of children suspected of having disorders of surfactant proteins is still under discussion. In this study, we aimed to describe the morphological characteristics and to evaluate the immunohistochemical expression of surfactant proteins (surfactant protein A [SPA], surfactant protein B, and pro-surfactant protein C) in the preterm twins that deceased due to unexplained respiratory distress syndrome (n = 12). Results showed statistically significant positive correlations between surfactant protein B expressions and pulmonary hemorrhage (ρ = 0.678; P < .05), SPA levels, and Apgar score (ρ = 0.605; P < .05) and also expressions of SPA and bronchopneumonia (ρ = 0.695; P < .05). The fetuses and neonates of the same gestational age showed differences among surfactant proteins regarding the immunostaining expression. Our data evidence a marked interindividual variability in the expression of all 3 surfactant proteins among the cases analyzed (n = 12), suggesting the intervention of some individual and epigenetic factors during gestation that might influence surfactant protein production and consequently survival rate.
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http://dx.doi.org/10.1097/MD.0000000000029701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333506PMC
July 2022

Phenolic Secondary Metabolites and Antiradical and Antibacterial Activities of Different Extracts of (L.) Weber ex F.H.Wigg from Călimani Mountains, Romania.

Pharmaceuticals (Basel) 2022 Jul 4;15(7). Epub 2022 Jul 4.

Department of Microbiology and Immunology, Faculty of Dental Medicine, Ovidius University of Constanta, 7 Ilarie Voronca Street, 900684 Constanta, Romania.

Phenolic compounds represent an essential bioactive metabolites group with numerous pharmaceutical applications. Our study aims to identify and quantify phenolic constituents of various liquid and dry extracts of (L.) Weber ex F.H. Wigg () from Calimani Mountains, Romania, and investigate their bioactivities. The extracts in acetone, 96% ethanol, and water with the same dried lichen/solvent ratio (/) were obtained through two conventional techniques: maceration (UBA, UBE, and UBW) and Soxhlet extraction (UBA, UBE, and UBW). High-performance liquid chromatography with diode-array detection (HPLC-DAD) was performed for usnic acid (UA) and different polyphenols quantification. Then, the total phenolic content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity (AA) were determined through spectrophotometric methods. Using the disc diffusion method (DDM), the antibacterial activity was evaluated against Gram-positive and Gram-negative bacteria known for their pathogenicity: (ATCC 25923), (ATCC 49619), (ATCC 27853), and (ATCC 13883). All extracts contain phenolic compounds expressed as TPC values. Five lichen extracts display various UA contents; this significant metabolite was not detected in UBW. Six polyphenols from the standards mixture were quantified only in ethanol and water extracts; UBE has all individual polyphenols, while UBE shows only two. Three polyphenols were detected in UBW, but none was found in UBW. All extracts had antiradical activity; however, only ethanol and acetone extracts proved inhibitory activity against , , and . In contrast, was strongly resistant (IZD = 0). Data analysis evidenced a high positive correlation between the phenolic constituents and bioactivities of each extract. Associating these extracts' properties with both conventional techniques used for their preparation revealed the extraction conditions' significant influence on lichen extracts metabolites profiling, with a powerful impact on their pharmacological potential.
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http://dx.doi.org/10.3390/ph15070829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322614PMC
July 2022

Characterization of the Tumor Microenvironment and the Biological Processes with a Role in Prostatic Tumorigenesis.

Biomedicines 2022 Jul 12;10(7). Epub 2022 Jul 12.

Medicine Faculty, "Ovidius" University of Constanta, 1 Universitatii Street, 900470 Constanta, Romania.

Prostate intratumoral heterogeneity, driven by epithelial-mesenchymal plasticity, contributes to the limited treatment response, and it is therefore necessary to use the biomarkers to improve patient prognostic survival. We aimed to characterize the tumor microenvironment (T lymphocyte infiltration, intratumoral CD34, and KI-67 expressions) by immunohistochemistry methods and to study the biological mechanisms (cell cycle, cell proliferation by adhesion glycoproteins, cell apoptosis) involved in the evolution of the prostate tumor process by flow-cytometry techniques. Our results showed that proliferative activity (S-phase) revealed statistically significant lower values of prostate adenocarcinoma (PCa) and benign prostatic hyperplasia (BPH) reported at non-malignant adjacent cell samples (PCa 4.32 ± 4.91; BPH 2.35 ± 1.37 vs. C 10.23 ± 0.43, < 0.01). Furthermore, 68% of BPH cases and 88% of patients with PCa had aneuploidy. Statistically increased values of cell proliferation (CD34+ CD61+) were observed in prostate adenocarcinoma and hyperplasia cases reported to non-malignant adjacent cell samples (PCa 28.79 ± 10.14; BPH 40.65 ± 11.88 vs. C 16.15 ± 2.58, 0.05). The CD42b+ cell population with a role in cell adhesion, and metastasis had a significantly increased value in PCa cases (38.39 ± 11.23) reported to controls (C 26.24 ± 0.62, < 0.01). The intratumoral expression of CD34 showed a significantly increased pattern of PCa tissue samples reported to controls (PCa 26.12 ± 6.84 vs. C 1.50 ± 0.70, < 0.01). Flow cytometric analysis of the cell cycle, apoptosis, and adhesion glycoproteins with a critical role in tumoral cell proliferation, T cell infiltrations, Ki-67, and CD 34 expressions by IHC methods are recommended as techniques for the efficient means of measurement for adenocarcinoma and hyperplasia prostate tissue samples and should be explored in the future.
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http://dx.doi.org/10.3390/biomedicines10071672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313300PMC
July 2022

Morphological and Ancillary Features of Uterine Leiomyosarcoma: Case Report.

Clin Pathol 2022 Jan-Dec;15:2632010X221105224. Epub 2022 Jun 27.

Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, Constanţa, Romania.

We report a rare case of giant uterine leiomyosarcoma in a postmenopausal woman, whose diagnosis was initially suspected at the evaluation of the abdominal efusion, and confirmed after the pathological examination of the uterus in association with the ancillary tests. The evaluation of the abdominal fluid showed single or clusters of malignant, round or spindle-shaped cells. On microscopic examination of the surgical specimen, a dense cell proliferation of spindle cells, with moderate to severe nuclear pleomorphism and significant mitotic activity was observed. Immunohistochemical evaluation demonstrated the loss of myocytic differentiation by focal, weakly positive expression of smooth muscle actin and desmin. The data presented in this case emphasize the relevance of the cytological examination, although the latter has only indicative value, especially since it is an aggressive tumor, frequently associated with mutant expression of p53. In our case, the first indication of the presence of uterine sarcoma was given by the presence of atypical cells in the peritoneal fluid.
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http://dx.doi.org/10.1177/2632010X221105224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240338PMC
June 2022

HPV and HIV Coinfection in Women from a Southeast Region of Romania-PICOPIV Study.

Medicina (Kaunas) 2022 Jun 3;58(6). Epub 2022 Jun 3.

Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, Ovidius University of Constanta, 145 Tomis Blvd., 900591 Constanta, Romania.

: Romania faces one of the highest cervical cancer burdens in Europe though it is a preventable cancer through population screening by cytology and human papillomavirus (HPV) detection. Also, it has one of the highest incidences of human immunodeficiency virus (HIV) infection. HPV and HIV coinfection are frequently encountered. The aim of study was to establish the prevalence of HPV infection among HIV-positive women in Southeast Region of Romania, to genotype high risk HPV types -and to correlate the results with clinical data and cytological cervical lesions. : 40 HIV-positive women were screened for HPV types and for cytological cervical lesions. The findings were evaluated in correlation with CD4 cell counts, HIV viral load, age at first sexual intercourse, number of sexual partners, vaginal candidiasis, and Gardnerella using statistical methods. : 19/40 (47.5%) women were positive for HPV types, 63.15% infected with single HPV type and 36.85% with multiple HPV types. The most frequent types were type: 31 (42.1%), 56 (31.57%), 53 (15.78%). On cytology, 34 (85%) women were found with NILM of which 38.23% were HPV-positive. Fifteen percent of women had abnormal cytology (three ASC-US, three LSIL), and all of them were HPV-positive. Through analyzing the value of CD4 count, women with CD4 count ≤ 200 cells/μL were found to be significantly more likely to be infected with HPV; meanwhile there was no correlation between the detection of HPV types and HIV viral load. Candida or Gardnerella were more often associated with HIV-positive women with HPV, than in women without HPV. Infection with HPV types is common among HIV-positive women in the Southeast Region of Romania and it is associated with age at the beginning of sexual life, number of sexual partners, CD4 value, vaginal candidiasis, and Gardnerella infection.
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http://dx.doi.org/10.3390/medicina58060760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231193PMC
June 2022

Changes in Platelet Function in Preterm Newborns with Prematurity Related Morbidities.

Children (Basel) 2022 May 27;9(6). Epub 2022 May 27.

Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, Ovidius University of Constanta, CEDMOG, 145 Tomis Blvd., 900591 Constanta, Romania.

Platelet indices represent useful biomarkers to express the thromboembolic status, inflammatory response, and oxidative stress in preterm newborns. Our study presented platelet count and function changes in prematurity-related morbidities such as respiratory distress syndrome, intraventricular bleeding, and anemia of prematurity in preterm newborn cases reported to healthy full-term newborns by flow cytometry and hematological methods. The platelet volume represents the average size of platelets in the blood samples, showing the significantly increased values in preterm newborns compared with healthy full-term newborns due to increasing activated platelet production. Flow cytometric analysis of immature platelet fractions (IPF) made using thiazole orange staining to detect their mRNA content and a glycoprotein (anti-GPIIIa) antibody for platelet gating. CD61-TO expression from premature newborns was significantly lower compared to healthy full-term neonates. Preterm newborn cases with respiratory distress syndrome and a need for respiratory support (RDS+) were characterized by a significantly increased platelet volume and a decreased immature platelet fraction reported in RDS- cases. Evaluating the platelet function in the newborn is difficult because the laboratory methodologies work with small quantities of newborn blood samples. The immature platelet fractions and platelet volume promise to be diagnostic biomarkers for diseases.
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http://dx.doi.org/10.3390/children9060791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221979PMC
May 2022

Concurrent Tumors Revealed by an Autopsy-A Case Report and Literature Review.

Case Rep Gastrointest Med 2022 1;2022:2308065. Epub 2022 Jun 1.

Department of Clinical Pathology, "St. Apostle Andrew" Emergency County Hospital, Constanta, Romania.

Introduction: Multiple primary malignant neoplasms are an uncommon phenomenon, given the very low incidence of two or more different tumors, while neoplasm may be limited to a single organ or may involve multiple separate anatomical organs. The main purpose of this study is to highlight the importance of morphological and immunohistochemical tests to distinguish the origin of the primary tumor. . We report the case of a 65-year-old deceased male, presenting multiple tumors in the lung, stomach, kidneys, and adrenal organs. The main symptoms presented by the patient were dyspnea with a range of 77% with oxygen saturation, fatigability, and productive cough. Histopathological examination revealed a solid and papillary lung adenocarcinoma, concurrent with tubular gastric adenocarcinoma. Immunohistochemical testing was mandatory by using a panel of seven monoclonal mouse antibodies (TTF-1, Napsin A, CK7, CK20, p40, synaptophysin, and chromogranin A). The pulmonary tumoral immunophenotype (positive for TTF-1, Napsin A, CK7; negative for CK20, p40, synaptophysin, and chromogranin A) confirms the diagnosis of primary lung ADC and invalidates the hypothesis of a metastasis arisen from a gastric adenocarcinoma or other forms of lung cancer.

Conclusion: The importance of the ancillary test is to distinguish a primary tumor from a metastatic one.
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http://dx.doi.org/10.1155/2022/2308065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177346PMC
June 2022

A Case of Giant Mesenchymal Uterine Tumor: Lipoleiomyoma.

Am J Case Rep 2022 Jan 19;23:e934913. Epub 2022 Jan 19.

Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, Constanţa, Romania.

BACKGROUND Uterine lipoleiomyoma is a rare benign tumor composed of varying proportions of smooth muscle fibers and mature adipocytes, without identification of hemorrhage, necrosis, or cyto-architectural atypia. It is part of the leiomyomas category, with an incidence of 0.03-0.2%. The pathogenesis of this lesional category is still unclear, but there are several theories that could explain the occurrence. Magnetic resonance imaging is the most useful diagnostic imaging method. There are a number of pathologies whose exclusion is necessary, with the differential diagnosis being made mainly based on microscopic examination and completed with immunohistochemical tests. Their treatment, when necessary, is surgical, with an excellent post-therapeutic evolution and prognosis. CASE REPORT We present the case of an elderly, postmenopausal patient who presented with abdominal pain, abnormal vaginal bleeding, and pollakiuria. The associated pathologies of the patient correspond to those mentioned in the literature, the particularities of the case being given by the large size of the tumor and the association with 2 other typical leiomyomas. Immunohistochemical markers used to exclude other diagnoses (desmin, h-caldesmon, S100, calretinin, MDM2, CD34) confirmed the diagnosis of uterine lipoleiomyoma. Because the patient was symptomatic and a large nodular mass was identified by ultrasound, surgical treatment was performed. CONCLUSIONS Although it is a benign lesion with an excellent prognosis, the pathogenetic mechanisms are not fully known. Theories of pathogenesis range from misplacing embryonic adipocytes to connective tissue fatty degeneration, and further studies are needed to establish the origin of this lesion.
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http://dx.doi.org/10.12659/AJCR.934913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793791PMC
January 2022

Assessment of programmed death-ligand 1 receptor immunohistochemical expression and its association with tumor-infiltrating lymphocytes and p53 status in triple-negative breast cancer.

Rom J Morphol Embryol 2021 Jan-Mar;62(1):63-71

Department of Nephrology, Clinical Service of Pathology, Sf. Apostol Andrei Emergency County Hospital, Faculty of Medicine, Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology (CEDMOG), Ovidius University of Constanţa, Romania;

Breast cancer (BC) is the second most frequent type of cancer for both sexes combined, after lung cancer. Triple-negative BC (TNBC) molecular subtype is characterized by lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) immunoexpression or amplification and represent 10-20% of all BC cases. The issue of the present study was to analyze the associations between programmed death-ligand 1 (PD-L1) immunoexpression and distribution of stromal tumor-infiltrating lymphocytes (stTILs) combined with clinico-morphological features of patients with TNBC. Secondly, our research evaluated PD-L1 immunoexpression as a prognostic factor and its correlation with p53 immunoexpression. Thirty cases with primary TNBC without prior neoadjuvant therapy were included in this research. stTILs were identified in all cases, most of them with low distribution (66.7%). A positive immunoreaction for PD-L1 was observed in 40% of cases. The PD-L1 immunoexpression was statistically significant associated with age, pathological tumor size, lymphovascular invasion, stTILs level, the presence of cluster of differentiation 8-positive (CD8+) TILs and p53 immunoexpression. In the present study, a positive PD-L1 immunoexpression was associated with a worse distant metastasis free survival (DMFS). We also found not only that high stTILs level were associated with a better DMFS but also that there was a statistically significant association between stTILs level and PD-L1 immunoexpression. Our results bring new insights to the fine connections between tumor microenvironment and molecular changes of TNBC. It helps us to better understand these aggressive tumors to identify the more useful biomarkers for predicting the response to adjuvant therapy and can represent a method for selecting the most suitable patients for immunotherapy.
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http://dx.doi.org/10.47162/RJME.62.1.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597365PMC
October 2021

Usnic Acid and (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels.

Antioxidants (Basel) 2021 Jul 23;10(8). Epub 2021 Jul 23.

Department of Microbiology and Immunology, Faculty of Dental Medicine, Ovidius University of Constanta, 7 Ilarie Voronca Street, 900684 Constanta, Romania.

Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, (L) F.H. Wigg () and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.
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http://dx.doi.org/10.3390/antiox10081171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388874PMC
July 2021

Biomarkers involved in evaluation of platelets function in South-Eastern Romanian patients with hematological malignancies subtypes.

Medicine (Baltimore) 2021 May;100(20):e25944

Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, "Ovidius" University of Constanta, CEDMOG.

Abstract: At present, various researches presented how subtypes of hematological malignancies are related to stages of the immune response, because the activated immune system represents a promising form in cancer treatment. This study explores the relationship between the adaptive immune system (T cells), and the coagulation system (platelets, platelet membrane glycoproteins, platelets derivate microparticles) which seems to play an important role in host immune defense of patients with acute myeloblastic leukemia (AML) or B cell lymphoma (BCL), 2 of the most common hematological malignancies subtypes.Blood samples (n = 114) obtained from patients with AML or BCL were analyzed for platelet membrane glycoproteins (CD42b, CD61), glycoprotein found on the surface of the T helper cells (CD4+), protein complex-specific antigen for T cells (CD3+), platelet-derived microparticles (CD61 PMP) biomarkers by flow cytometry, and hematological parameters were quantified by usual methods.In patients with AML, the means of the percentage of the expressions of the molecules on platelet surfaces (CD61 and CD42b, P < .01; paired T test) were lower as compared to both control subgroups. The expression of cytoplasmic granules content (CD61 PMP) had a significantly higher value in patients with AML reported to controlling subgroups (P < .01; paired T test), which is suggesting an intravascular activation of platelets.The platelet activation status was presented in patients with low stage BCL because CD61 and CD42b expressions were significantly higher than control subgroups, but the expression of CD 61 PMP had a significantly decreased value reported to control subgroups (all P < .01; paired T test). T helper/inducer lineage CD4+ and T lymphoid lineage CD3+ expressions presented significant differences between patients with AML or low stage BCL reported to control subgroups (all P < .01; paired T test).Platelet-lymphocyte interactions are involved in malignant disorders, and CD61, CD42b present on platelet membranes, as functionally active surface receptors mediate the adhesion of active platelets to lymphocytes, endothelial cells, and cancer cells.
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http://dx.doi.org/10.1097/MD.0000000000025944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137019PMC
May 2021

Dinosaur Tail Appendix in Trisomy 13.

Fetal Pediatr Pathol 2022 Aug 13;41(4):698-700. Epub 2021 May 13.

Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, Constanța, România.

Among the many malformations associated with trisomy 13, one of the less recognized is dinosaur tail appendix. We illustrate a dinosaur-tail appendix from an autopsy in a newborn female with trisomy 13. This malformation has a frequency between 0.014% and 3.7% in general population. Trisomy 13 is a relatively well-known chromosomal disorder in which dinosaur tail appendix can be found. This entity should be considered element of a complete morphological diagnosis.
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http://dx.doi.org/10.1080/15513815.2021.1926020DOI Listing
August 2022

The diagnostic value of miR-92a, -143, and -145 expression levels in patients with colorectal adenocarcinoma from Romania.

Medicine (Baltimore) 2020 Aug;99(35):e21895

Pathology Department, Sf. Apostol Andrei Clinical Emergency County Hospital.

MicroRNAs (miRNAs) refers to a small, short non-coding RNA of endogenous class. They have shown to have an increasingly altered expression in many types of cancer, including colorectal cancer (CRC).In the present study, miRNA TaqManMGB and qRT-PCR was used to quantify the expression and clinical significance of 3 mature human miRNA in 82 pairs of colorectal adenocarcinoma tissues and normal adjacent tissue samples (NATS) collected from patients of the south-east part of Romania. Differences between CRC and NATS were analyzed using Wilcoxon test, while correlations between miRNAs expression levels and clinicopathological features were examined using non-parametric tests. In addition, the ability of selected miRNAs to function as biomarkers and, as potential indicators in CRC prognosis was also examined.When the miRNA expression was compared in CRC related NATS, miR-143, and miR-145 were significantly underexpressed (4.99 ± -1.02 vs -5.66 ± -1.66, P < .001; -4.85 ± -0.59 vs -9.27 ± -1.51, P < .001, respectively), while the pattern of miR-92a was significantly overexpressed (-5.55 ± -2.83 vs -4.92 ± -2.44, P < .001). Moreover, the expression levels of selected miRNAs were identified to be correlated with gradual increases in fold change expression with the depth of tumor invasion, lymph node invasion, and maximal increases with distant metastasis. Furthermore, the receiver operating characteristic analysis demonstrated that potential diagnostic of miR-143, miR-145, and miR-92a in discriminating CRC from NATS, with the area under the curve of 0.74, 0.85, and 0.84 respectively. The Kaplan-Meier and the log-rank test showed that a high level of miR-92a and low levels of miR-143 and miR-145 predicted poor survival rate in our cohorts.In conclusion, we can summarize that miR-145 and miR-143 are decreased, while miR-92 is increased in CRC compared to NATS, and associated with different stages of CRC pathogenesis. Thus, the expression of selected miRNAs can represent potential diagnostic and prognostic tools in patients with CRC from Romania.
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http://dx.doi.org/10.1097/MD.0000000000021895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458237PMC
August 2020

Genetic Antibiotic Resistance of Helicobacter pylori in South-Eastern Romania.

J Gastrointestin Liver Dis 2020 Mar 13;29(1):19-25. Epub 2020 Mar 13.

Faculty of Medicine, Ovidius University of Constanta, Romania; Clinical Infectious Diseases Hospital, Constanta, Romania.

Background And Aim: Helicobacter pylori infection is very common worldwide, and it is associated with an important gastric pathology. Treatment of this infection is difficult and consists of the combination of two or three antibiotics. However, the rate of resistance to treatment is high. Antimicrobial resistance of Helicobacter pylori is based on its cultivation in the laboratory and testing of phenotypic susceptibility, a time-consuming, laborious method. This study aimed to detect the genetic resistance to antibiotics of Helicobacter pylori in the south-eastern region of Romania.

Methods: Ninety patients with positive rapid urease test gastric biopsy samples were tested. Genetic resistance to antibiotics (fluoroquinolone and clarithromycin) was tested by GenoType HelicoDR kit (Hain Lifescience GmbH, Germany).

Results: Clarithromycin resistance mutations were detected in 20% of patients, the commonest mutation in our study beeing A2147G (associated with high level of clarithromycin resistance and lower cure rates). Fluoroquinolones resistance mutations were detected in 30% of patients, and the most common mutations were D91N, D91G, and N87K. There was no correlation with patients gender or age, with the exception of fluoroquinolone resistance, which was detected more frequently in females.   Conclusions. Clarithromycin and fluoroquinolone resistance of Helicobacter pylori is moderately high in our study. There is a need for monitoring Helicobacter resistance patterns in Romania to provide data that can guide empirical treatment. This is the first published study on the genetic resistance of Helicobacter pylori in Romania.
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http://dx.doi.org/10.15403/jgld-758DOI Listing
March 2020

A rare case of a double high-risk gastrointestinal stromal tumor of jejunum with KIT-negative∕PDGFRA-positive immunophenotype.

Rom J Morphol Embryol 2019 ;60(3):963-970

Clinical Service of Pathology, "Sf. Apostol Andrei" Emergency County Hospital, Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, "Ovidius" University of Constanţa, Romania;

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that represent the second most common type in the gastrointestinal system, but clinical outcomes vary due to complex molecular changes. The aim of our study is to highlight a unique case of a 5th decade male, presenting a double primary GIST of the jejunum, associated with a rare immunophenotype and with a high risk of malignancy. Ancillary studies were performed using several biomarkers [cluster of differentiation (CD) 117∕c-kit, discovered on GIST1 (DOG1), desmin, S-100, vimentin, cytokeratin 7 (CK7), Ki67, actin, platelet-derived growth factor receptor alpha (PDGFRA) and CD34], in order to confirm the diagnosis and to evaluate prognostic and predictive factors. A KIT-negative∕PDGFRA-positive immunophenotype was obtained in our case and it was associated with a poor prognosis. Its unfavorable clinical evolution was sustained by recurrence as malignant (GIST) with dedifferentiation and metastases developed in less than one year after the initial diagnosis. Clinico-morphological features of GISTs with an impact on survival must be identified and a tailored therapy should be applied for each case.
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June 2020

Molecular expression profiles of selected microRNAs in colorectal adenocarcinoma in patients from south-eastern part of Romania.

Medicine (Baltimore) 2019 Nov;98(47):e18122

Pathology Department, Sf. Apostol Andrei Clinical Emergency County Hospital Constanta.

MicroRNAs (miRNAs) are endogenous, non-coding class of RNAs with functions in the regulation of genes expressions. Dysregulated expressions of miRNAs play important roles in carcinogenesis and cancer progression by targeting various oncogenes and tumor-suppressor genes. miRNAs represent a new field for molecular diagnosis and prognosis of colorectal cancer (CRC) due to their high tissue specificity, their stability, and their dysregulated expression in tumor development.This study aimed to investigate using the qRT-PCR method the expression profile and prognostic value of 11 mature miRNAs in a cohort of 82 Romanian patients diagnosed with CRC. The relationship between the expression levels of selected miRNAs and clinicopathologic features were evaluated using ANOVA and Pearson test. In addition, the receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic values of the miRNAs to discriminate cancerous from non-cancerous states of the samples.The expression levels of miR-30c, miR-144, miR-375, miR-214, and miR-195 in CRC tissue were significantly downregulated (all P < .05; Paired T-Test) than that in normal adjacent tissue sample (NATS), while the expression of miR-141, miR-182, miR-183, miR-21, and miR-370 in CRC tissue were significantly upregulated (all P < .001) than that in NATS. Moreover, the expression levels of miR-182, miR-183, miR-141, and miR-21 were demonstrated to be associated with a gradual increase in fold change expression with depth of tumor invasion (all P < .05), lymph node invasion (all P < .001), and maximal increase with distant metastasis (all P < .001). Moreover, the analysis of ROC curves revealed that AUC (95% CI) of miR-182, miR-183, miR-141, and miR-21 in diagnosis of CRC was 0.76 (0.66-0.87), 0.85 (0.78-0.94), 0.77 (0.62-0.92), 0.83 (0.73-0.90), respectively. The univariate and multivariate Cox-proportional hazard regression for all variables revealed that the nodal status, distant metastasis, miR-21, miR-141, miR-182, and miR-183 were independent prognostic markers of CRC.In conclusion, altered expressions of miR-21, miR-141, miR-182, and miR-183 in CRC varies at different stages of CRC development and may serve as potential diagnosis molecular biomarkers in Romanian patients with CRC. Further investigations are needed to confirm our findings.
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http://dx.doi.org/10.1097/MD.0000000000018122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882641PMC
November 2019

A boy with 13.34-Mb interstitial deletion of chromosome 4p15: A new case report and review of the literature.

Medicine (Baltimore) 2017 Dec;96(51):e9301

Department of Pathology, Emergency Clinical County Hospital of Constanta, Romania CEDMOG Center, "Ovidius" University of Constanta, Romania Faculty of Medicine, "Ovidius" University of Constanta, Romania Department of Pediatrics, Emergency Clinical County Hospital of Constanta, Romania.

Rationale: To date, >40 cases have been described with interstitial deletions involving the 4p15 region.

Patient Concerns And Diagnosis: We report a case of a 3-year-old boy with an interstitial de novo deletion of approximately 13.34 Mb in 4p15.1-15.31 having mild developmental delay and multiple minor congenital abnormalities.

Lessons: This case presents a clinical manifestation that is similar but not identical to other reported cases. In this report, we have provided a detailed description of a 3-year-old patient with an interstitial 4p deletion and mildly affected phenotype. We discuss the possible involvement of SLIT2, KCNIP4, and LGI2 in cortical development and RBPJ in skeletal abnormalities.
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http://dx.doi.org/10.1097/MD.0000000000009301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758197PMC
December 2017

ETHICAL AND GENETIC ASPECTS REGARDING PRESYMPTOMATIC TESTING FOR NEURODEGENERATIVE DISEASES.

Rev Med Chir Soc Med Nat Iasi 2016 Jan-Mar;120(1):15-22

Neurodegenerative diseases, such as Alzheimer's dementia, Huntington's chorea, Parkinson's disease or spinocerebellar ataxia, manifests into adulthood with an insidious onset, slowly of progressive symptoms. All of these diseases are characterized by presimptomatic stages that preceded with many years of clinical debut. In Parkinson's disease, more than half of the dopaminergic neurons of the black substance are lost before the advent of motor characteristic manifestations. In Huntington's chorea, the progressive neurodegenerative disease could be diagnose prenatal and presymptomatic by analyse of the number of CAG repeats in exon 1 of the huntingtin gene. A similar mechanism represented by expansion of trinucleotide repeats during hereditary transmission from parents to children was identified in fragile X syndrome, spinocerebellar ataxia, spinal muscular and bulbar atrophy, or myotonic dystrophy. Presymptomatic diagnosis in all these progressive diseases raise many ethical issues, due to the psychological impact that can cause the prediction of a disease for which there is currently no curative treatment. Therefore, a positive result can produce serious psychological trauma and major changes in the lifestyle of the individual, instead, a negative result can bring joy and tranquillity. But the problem arises if presymptomatic testing in these neurodegenerative diseases brings greater benefits compared to the possible psychological damage, which can add the risk of stigmatization or discrimination.
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June 2016

Laryngeal primary malignant melanoma: a case report.

Rom J Morphol Embryol 2015 ;56(4):1513-6

Department of Pathology, Faculty of Medicine, "Ovidius" University, Clinical Service of Pathology, Emergency County Hospital, Constanta, Romania;

Malignant melanoma of the larynx is a rare cancer that can appear as a primary tumor or as a metastasis from a cutaneous head and neck primary lesion. We present a new case of primary laryngeal malignant melanoma diagnosed by histological examination of an excisional biopsy specimen. The patient was a 53-year-old man with a history of smoking and hoarseness but without any clinical evidence of other cutaneous malignant melanocytic lesions. Microscopically, the tumor consisted of polygonal-epithelioid cells admixed with more elongated, spindle-shaped cells. Some of the tumoral cells demonstrated dark brown cytoplasmic and nuclear melanin. Despite significant ulceration and disruption of the epithelium, in situ malignant melanocytes were recognized within the remaining epithelium. Immunohistochemical stains were strongly positive for S-100 protein, HMB-45 and Melan-A. On the other hand, cytokeratin stains were negative. Based on the clinical and histological findings, a diagnosis of primary malignant melanoma of the larynx was established.
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November 2016

Clinico-pathological and molecular subtypes of male breast carcinoma according to immunohistochemistry.

Rom J Morphol Embryol 2013 ;54(3 Suppl):749-55

Department of Pathology, Faculty of Medicine, "Ovidius" University; Clinical Service of Pathology, Emergency County Hospital, Constanta, Romania;

Introduction: Male breast carcinoma is a rare condition, but with a trend of increase frequency. In our study, we investigate the clinico-pathological features and overall survival at 35 male cases of primary invasive breast carcinoma correlated with molecular subtypes defined by immunohistochemical profile.

Methods: Based on immunohistochemical expression profiles of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2) and Ki67, EGFR and CK5/6, the male breast cancers were classified into the following molecular subtypes: Luminal A, Luminal B, HER2+, triple negative and unclassified.

Results: In our study, we identified 65.7% as Luminal A subtype and 28.6% as Luminal B subtype. The difference was represented by two (5.7%) cases of triple negative subtype, but due to low number of patients, no correlations or prognostic significance could be assessed in these cases. No HER2 or unclassified subtypes were identified.

Conclusions: Luminal A tumors are the most frequent subtype in MBC, with a better outcome than Luminal B subtype. We recorded high levels of ER and PR expression, which predict a better response to adjuvant hormonal therapy. At the time of diagnosis, most of the patients were aged and with an advance clinical stage, this requiring implementation of screening programs and increase education of population in order to an early detection.
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July 2014

Morphologic and immunohistochemical features of breast nevi.

Rom J Morphol Embryol 2013 ;54(2):371-5

Research Collective of Pathology Department, Emergency County Hospital, Constanta, Romania.

A large number of publications recognize that there are melanocytic lesions with microscopic features similar to melanoma, related to their location. Those locations are represented by the ear, the milk lines (axillary, breast, periumbilical and inguinal regions), palms, soles, and flexural regions. Starting from Rongioletti F et al. study in 2004, we measured 10 histological parameters on 96 nevi (39 from the breast) and notes with 0 if absent or impossible to evaluate and with 1 if present. The score for each lesion ranged from 0 to 7 and we compared the features of the breast nevi with the nevi from the control sites and found that breast nevi present more atypical features than the nevi from the other sites (absence of demarcation of melanocytes at lateral margins, nests and dyscohesive pattern and melanocytic atypia). We also performed immunohistochemical examination on lesions that presented three or more of the examined histological parameters, but the results were nor suggestive. The conclusion of this study is that the atypical features of the breast nevi are only site related atypias and have no hormonal influences.
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December 2013

Morphological characteristics of a mucinous adenocarcinoma of the prostate: differential diagnosis considerations.

Rom J Morphol Embryol 2013 ;54(1):191-4

Department of Pathology, Faculty of Medicine, "Ovidius" University, Constanta, Romania.

Mucoid adenocarcinoma of the prostate is a very rare variant, account less than 1% of prostatic adenocarcinomas. In this respect, the most common histopathological type of prostate cancer is acinar adenocarcinoma. Diagnosis of this variant is very important due to peculiarities: aggressive biologic behavior, poor response to radiotherapy. Although these tumors are not as hormonally responsive as acinar adenocarcinomas, some of them respond to androgen withdrawal. Before making a diagnosis of primary mucinous adenocarcinoma, is necessary to exclude an extraprostatic malignant neoplasia, especially from the bladder or bowel. We present the case of a male patient who suffered a transurethral prostatic resection surgery. Histopathological examination revealed malignant tumor cells floating in a pool of mucus or even acini mixed with signet ring cells. A particular aspect is that floating mucus cells have a non-papillary pattern similar to colloid carcinoma of the breast. The use of monoclonal antibody revealed positive immunoreaction of malignant cells for prostatic specific markers and excluded neoplastic invasion of the bladder or bowel carcinoma.
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May 2014

Atypical adenomatous hyperplasia of the prostate mimicking adenocarcinoma lesion: case report and literature review.

Rom J Morphol Embryol 2012 ;53(4):1093-6

Department of Pathology, Faculty of Medicine, Ovidius University, Constanta, Romania.

The diagnosis of prostate cancer is challenging because of the existence of lesions that mimic adenocarcinoma. Such a lesion is atypical adenomatous hyperplasia (AAH) or adenosis, which represents a proliferation of crowded, small to medium glands with basal cell layer invariably present, but often inconspicuous on routine stains. The importance of the lesion lies in the potential for being misdiagnosed as low-grade adenocarcinoma (Gleason 1 or 2). We present the case of a male patient, who suffered a transurethral prostatic resection surgery. Histopathological examination showed benign prostatic hyperplasia with a focus of crowded glands with a nodular appearance. The presence of basal cell was assessed using high molecular-weight cytokeratin (HMWCK), clone 34βE12 and p63 immunostaining, which revealed discontinuous positive immunostaining. In adenocarcinomas, the basal cell layer is absent. This case highlights the usefulness of 34βE12 antibodies, avoiding a false positive diagnosis of cancer, with negative consequences on the patient's psychological condition and treatment costs. We recommended the follow-up of the patient.
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May 2014

The prognostic value of the immunohistochemical aspects of tumor suppressor genes p53, bcl-2, PTEN and nuclear proliferative antigen Ki-67 in resected colorectal carcinoma.

Rom J Morphol Embryol 2012 ;53(3):549-56

Dr Alexandru Gafencu Emergency Military Hospital, Constanta, Romania.

Unlabelled: This study aim was to identify the relations between tumor suppressor genes (p53, bcl-2, PTEN), nuclear proliferative antigen Ki-67 and epidemiologic, morphologic and histologic patient related factors, in colorectal cancer.

Materials And Methods: Twenty-two prospectively collected colorectal cancer resection specimens were histologically prepared, using standard paraffin-embedded and Hematoxylin-Eosin staining method; for immunohistochemical study, the Streptavidin-Biotin (sABC)/Horseradish Peroxidase (HRP) method was used.

Results: P53 was positive in 86.36% of cases, more intense (>50%) in rectal cancer and in women 59.16 ± 9.49-year-old; the G1/2 adenocarcinoma was dominant. Bcl-2 was positive in 18.18% of the cases, in distal colorectal cancer, only in men, 63.5 ± 13.2-year-old. PTEN was positive in 95.45% of the cases; intense positivity was recorded in 12 men and six women, 61.47 ± 11.67-year-old, in rectal topography. Ki-67 was positive in 86.36% of the cases, more intense in four men and four women, 63.45 ± 12.22-year-old, in proximal and advanced colorectal cancers (pT3N1/2 - 62.5%).

Conclusions: Tumor suppressor genes mutations are often present in colorectal cancer; the intensity of the expression of these mutations varies, which could explain the different prognosis for these patients.
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April 2013

Pulmonary alveolar lipoproteinosis associated with emphysematous areas.

Rom J Morphol Embryol 2012 ;53(1):173-7

Department of Pathology, Faculty of Medicine, Ovidius University, Constanta, Romania.

Pulmonary alveolar lipoproteinosis, described for the first time in 1958 by Rosen SH, Castleman B and Liebow AA, is a rare pathological condition characterized by alveolar accumulation of lipoproteinaceous material. It is the result of macrophages impairment to rid the alveolar spaces of spent surfactant. This condition involves a restrictive function of pulmonary tissue, reflected in gas exchange impairment and respiratory symptoms of variable severity. Until now, about 410 cases have been reported in the literature. From these cases, 90% were represented by primary type of pulmonary alveolar lipoproteinosis. We present the case of 37-year-old male patient admitted in the Department of Internal Medicine, Emergency County Hospital, Constanta, Romania, with progressive exertional dyspnea, dry cough and perioral cyanosis. The clinical symptoms started three months before hospital admission. Based on clinical findings and imaging features, the primary pulmonary alveolar proteinosis diagnosis has been suspected. Uncharacteristic serous aspect of fluid resulting from bronchoalveolar lavage required open lung biopsy. Pathologic examination of pulmonary slice revealed features consistent with the diagnosis of pulmonary alveolar lipoproteinosis associated with emphysematous foci. The peculiarity of this case lies in the association of two pathological conditions, each of them requiring different pathways.
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July 2012

Differential diagnosis of a gastric stromal tumor: case report and literature review.

Rom J Morphol Embryol 2011 ;52(4):1361-8

Department of Pathology, Faculty of Medicine, Ovidius University, Constanta, Romania.

Gastrointestinal stromal tumors account for 0.1-3% of all gastrointestinal neoplasms and are characterized by features that overlap with those of other mesenchymal tumors. We expose the case of a 58-year-old male patient who complained of abdominal pain, weakness and melena. Microscopic examination of surgically resected gastric tumor revealed a neoplastic proliferation composed of spindle cells with eosinophilic cytoplasm, elongated nuclei with rounded ends, palisadic disposition and intracytoplasmic perinuclear vacuoles, low cyto-nuclear polymorphism, mild atypia and mitotic activity of 3-5÷50 HPF. Some histopathological features requested differential diagnosis with schwannoma and tumors of myocytary origin, based on immunohistochemical techniques, which have established a final diagnosis of spindle cell gastric stromal tumor. We also reviewed the GIST-related literature and evaluated the possible methods of preoperative diagnosis of GISTs based on endoscopic biopsy. Proper classification of GISTs based on histopathological criteria and immunohistochemical techniques has a great prognostic and therapeutic utility. Future development of endoscopic biopsy methods will refine the management of gastrointestinal stromal tumors.
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April 2012

Urothelial carcinoma of the renal pelvis associated with cystic disease of the kidney.

Rom J Morphol Embryol 2011 ;52(1 Suppl):497-501

Department of Pathology, Emergency County Hospital, Constanta, Romania.

Primary tumors of the renal pelvis and ureter account for about 8% of all urinary tract tumors. More than 90% of them are urothelial carcinomas. On the other hand, unilateral multicystic renal disease is an uncommon pathologic condition that may be mistaken for unilateral autosomal dominant polycystic kidney disease, multilocular cystic nephroma or cystic neoplasm. We present the case of a 54-year-old male known with arterial hypertension, admitted in the Second Surgery Department of Emergency County Hospital, Constanta, with intense right flank and right lumbar pain. This symptom started one month before hospital admission. Based on clinical features and imaging evaluations we established a presumptive diagnosis of unilateral autosomal dominant polycystic kidney disease. For these reasons, total right nephrectomy was performed. Pathologic examination of the nephrectomy specimen revealed high-grade urothelial carcinoma of the renal pelvis associated with unilateral multicystic renal disease. The particularity of this case lies in the uncommon association between two rare renal pathological conditions diagnosed by pathological examination.
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June 2011

Morphological and immunohistochemical characteristics of a gastric amphicrine tumor: differential diagnosis considerations.

Rom J Morphol Embryol 2011 ;52(1 Suppl):485-8

Department of Pathology, Faculty of Medicine, "Ovidius" University, Constanta, Romania.

Gastric amphicrine tumors, lesions in which dual epithelial and neuroendocrine differentiation occurs in the same cell, represent neoplasms with a very low incidence. We present the case of a male patient, who suffered a subtotal gastrectomy. Histopathological examination showed a malignant proliferation with glandular, solid and trabecular pattern, composed of round/polygonal, monomorphic cells admixed with scattered signet ring cells. The use of monoclonal antibodies revealed positive immunoreaction of malignant cells for epithelial and neuroendocrine markers. These characteristic features plead for the final diagnosis of amphicrine tumor, based on the co-expression of both epithelial and neuroendocrine markers in the same cells. Differentiation of this entity must be done with collision tumor and with composite tumor, with distinct histopathological features. Rigorous interpretation of dual immunohistochemical expression of neoplastic cells of amphicrine tumor is useful in distinguishing this entity from others with similar morphological characteristics, in order to assure an adequate targeted therapy.
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June 2011

Nuclear comparative morphometric study between DCIS and normal resting mammary gland tissue.

Rom J Morphol Embryol 2011 ;52(1 Suppl):303-8

Department of Pathology, Faculty of Medicine, "Ovidius" University, Constanta, Romania.

Ductal carcinoma in situ (DCIS) is the malignant epithelial cell proliferation that affect only ducts, including lobular, without basement membrane interruption. Benign or malignant cell phenotype is defined by nuclear appearance. Morphometric analysis could provide quantitative information about nuclear profile in several lesions. In this study, we assess nuclear morphometric features of mammary epithelial cells in DCIS compared to normal resting mammary gland tissue. For morphological evaluation, we included two groups of mammary gland tissue. The first group comprised breast tissue from 20 women surgically treated and histopathologically confirmed with DCIS. The second control group was represented by normal resting mammary tissue obtained from another 20 women surgically treated for fibroadenoma. Evaluated morphometric parameters were: nuclear area (NA), nuclear perimeter (P), maximum diameter (Dmax), minimum diameter (Dmin), elongation factor (E). Morphometric assessment of DCIS nuclei showed significant higher values than normal resting breast tissue. Morphometric analysis gave information about tumor aggressiveness, invasion tendency and disease prognostic.
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June 2011

The importance of monitoring protocols in cervical carcinoma screening.

Rom J Morphol Embryol 2011 ;52(1 Suppl):297-302

Department of Pathology, Faculty of Medicine, "Ovidius" University, Constanta, Romania.

Romania has supremacy in terms of European statistical indicators of cervical cancer, a fact attested by the studies made by international organizations. The present study is based on cytological evaluation of a group of 9269 cervico-vaginal smears, segregated in various groups that were monitored by standard diagnostic and therapeutic protocols, attitude based on an excellent collaboration with the gynecologist. This cooperation led to the elaboration of a set of protocols for follow-up of patients assessed by Babes-Papanicolaou test, in order to assure an adequate management for all cervical lesions. An important feature of this study is that histopathological examination of cases cytologically designated as HSIL showed, along with changes of HSIL-CIN2 and HSIL-CIN3, also carcinoma in situ and invasive squamous cell carcinoma lesions, emphasizing the importance of the pathologic diagnosis of certainty. This idea is also supported in cases of glandular cell atypia, whose microscopic evaluation identified premalignant and malignant lesions, both in endometrial and endocervical site. A particular aspect of the analyzed batch consists in the description of a subgroup of false-negative cytodiagnostic results associated with cervical carcinoma, highlighting the causes and the possibilities to avoid further errors. Overall analysis of results reveals major involvement of the pathologist in providing the sequence from cytology to histopathological diagnosis and to establish diagnostic continuity.
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June 2011
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