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Abstract Background Endometrial carcinoma (EC) is the most common malignancy of the female genital tract. Gene alterations and overexpression of various oncogenes are important in tumor development. The human HER 2 neu (c-erbB-2) gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network. The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer, to study its correlation to established prognostic parameters and estrogen receptor (ER) and progesterone receptor (PR) status. Methods Immunohistochemical (IHC) analyses of ER, PR and c-erbB-2 were performed in 72 EC cases. Results We detected a positive staining with c erbB 2 in 18.1% of the cases and determined a statistically significant relation between c-erbB-2 and PR. We could not find a statistically significant relation between c-erbB-2 staining and ER. There was not a statistically significant difference between c-erbB-2 and histological grade. The highest level of c-erbB-2 was found in grade 2 cases. There was not any statistically significant relation between c-erbB-2 and menstrual status, myometrial invasion, lymph node status, stage and survival. Conclusions Although our study provides additional evidence of the potential prognostic role of c-erbB-2, further prospective and controlled studies are required to validate their clinical usefulness.

Objective: This review which aims to examine the recent and current status of pathology education in medical schools, and covers the publications related to undergraduate pathology education published between 2010 January and June 2023., Material and Method: A search was performed through PubMed, Google Scholar, Semantic Scholar, and Ulakbim search engines for the Science Citation Index, Science Citation Index Expanded, Emerging Sources Citation Index, Directory of Open Access Journals, Scopus, PubMed as well as TR Dizin indexed articles. The findings are categorized into two periods as 2010 January - 2020 April (pre-COVID-19 pandemic) and May 2020 - 2023 June. A total of 24 reviews/editorials/letters to the editor and 63 research articles in the pre-pandemic period and 11 reviews/ editorials/ letters to the editor and 35 research articles between 2020 May and 2023 June are included in the analysis., Results: Currently, medical education generally depends on core education programs with defined learning objectives and outcomes. Moreover, problem-based, case-based, and team-based interactive learning are being used along with traditional didactic courses. Additionally, digital/ web-based/remote education methods have gained prominence after the COVID-19 pandemic. The virtual or augmented reality and 3D drawing applications are offered as a solution for the autopsy and macroscopy courses. A scarce number of publications are found on measuring and evaluating the effectiveness of learning., Conclusion: Artificial intelligence in pathology education is a topic that looks likely to become important in the near future. National and international comprehensive standardization is a necessity. A joint effort and collective intelligence are needed to achieve the desired goals in undergraduate pathology education.

Wearable devices based on microneedle (MN) technology have recently emerged as tools for in situ transdermal sensing or delivery in interstitial fluid (ISF). Particularly, MN-based electrochemical sensors allow the continuous monitoring of analytes in a minimally invasive manner through ISF. Exogenous small molecules found in ISF such as therapeutic drugs are ideal candidates for MN sensors due to their correlation with blood levels and their relevance for the optimal management of personalized therapies. Herein, a hollow MN array patch is modified with conductive pastes and functionalized with cross-linked chitosan to develop an MN-based voltammetric sensor for continuous monitoring of methotrexate (MTX). Interestingly, the chitosan coating avoids biofouling while enabling the adsorption of MTX at the electrode's surface for sensitive analysis. The MN sensor exhibits excellent analytical performance in vitro with protein-enriched artificial ISF and ex vivo under a Franz diffusion cell configuration. The MN sensor shows a linear range from 25 to 400 μM, which fits within the therapeutic range of high-dose MTX treatment for cancer patients and an excellent continuous operation for more than two days. Moreover, an iontophoretic hollow MN array patch is developed with the integration of both the anode and cathode in the single MN array patch. The ex vivo characterization demonstrates the transdermal on-demand drug delivery of MTX. Overall, the combination of both MN patches represents impactful progress in closed-loop systems for therapeutic drug management in disorders such as cancer, rheumatoid arthritis, or psoriasis.

Background: Though the recommended sampled lymph node number in colorectal carcinomas is at least 12, due to shrinkage after preoperative neoadjuvant chemoradiotherapy (NCRT), it can be difficult to attain that number., Aim: Our aim is to increase the lymph node number by applying alcohol fixation on the formalin-fixed resection materials of the patients that received or not received neoadjuvant therapy and to evaluate the changes in staging due to obtained lymph nodes., Settings and Design: Non-randomized controlled trial., Materials and Methods: Lymph node dissection was performed in the resection materials with rectum tumor which were formalin- and afterwards, alcohol-fixed. The number of lymph nodes obtained by both of the methods and status of metastasis were evaluated statistically., Results: Of the total 76 rectal tumors, 57 had and 19 had not received NCRT. The number of lymph node was adequate in 89.5% cases with no NCRT and in 63.2% cases with NCRT. While no change was observed after the alcohol fixation in the cases fulfilling adequacy criterion among those with no NCRT (p = 1.000), the adequacy rate increased from 63.2% to 87.7% in those with NCRT (p < 0.001). Although statistically insignificant, there was a change in pN stage in eight cases. In three of them, the stage varied from pN0 to pN1c, and in five cases, from pN1a to pN1b., Conclusion: Using solutions as alcohol during fixation might facilitate the identification of metastatic lymph nodes, might change the stage of the disease and therefore, might affect the patient-based therapy.

Cardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are noncoding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague-Dawley male rats were divided into the training group (TG, n =9) and the control group (CG, n =6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity ( p =0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.

Objectives: In gastrointestinal stromal tumors (GIST), malignancy potential is determined by the prognostic disease risk stratification based on mitosis, tumor size, and location. Phosphohistone H3 (PHH3) is an immunohistochemical marker showing mitotic activity in cells. In this study, we aimed to evaluate mitosis in GIST with PHH3, compare the results with hematoxylin and eosin (HE) stained slides, and examine its relationship with other prognostic data., Methods: Clinicopathological findings and survival were determined in GIST cases diagnosed between 2006 and 2017. The prognostic risk score was calculated according HE- and PHH3-based mitosis. The cases were classified as Group I: HE + and PHH3 + and Group II: HE + and PHH3-. They were also grouped as those diagnosed before and after 2012 and the staining results of HE and PHH3 were re-analyzed., Results: Ninety-eight cases were included in the study. Mitosis was detected with both HE and PHH3 in 63.3% of the cases (62/98 cases) (Group I) while in 36.7% of cases, it was detected with HE but not with PHH3 (Group II). In only two cases, the risk score changed with PHH3 (very low → intermedier grade). The ratio of HE + and PHH3 + cases in 2012 and after was significantly higher than HE + and PHH3 - cases. A statistically significant relation was found between HE- and PHH3-based risk scores (p<0.05). There was a significant difference between HE-based risk score groups in terms of survival (p<0.05), while no difference was observed between the PHH3-based risk score groups (p>0.05)., Conclusion: In GIST cases, PHH3 can be used to determine mitosis in more recent blocks, taking into account the technical conditions of the laboratory, but it does not seem to be superior to mitosis detected by HE. Research should continue on new survival determinants for GIST., Competing Interests: None declared., (© Copyright 2022 by The Medical Bulletin of Sisli Etfal Hospital.)

Silver nanowire (Ag NW) networks have great potential to replace commercial transparent conducting oxides due to their superior properties in conjunction with their competitive cost, availability and mechanical flexibility. However, there are still challenges to overcome for the large scale utilization of Ag NWs in devices due to oxidation/sulfidation of NWs, which leads to performance loss. Here, we develop a solution-based strategy to deposit a thin platinum (Pt) shell layer (15 nm) onto Ag NWs to improve their chemical, environmental and electrochemical stabilities. Environmental and thermal stabilities of the core-shell NW networks were monitored under different relative humidity conditions (RH of 43, 75 and 85%) and temperature settings (75 °C for 120 hours and 150 °C for 40 hours) and compared to those of bare Ag NWs. Afterwards, stability of core-shell NW networks in hydrogen peroxide was investigated and compared to that of bare Ag NW networks. The potential window for electrochemical stability of the Ag NW networks was broadened to 0-1 V (vs. Ag/AgCl) upon Pt deposition, while bare Ag NWs were stable only in the 0-0.6 V range. Moreover, Ag-Pt core-shell NWs were used for the detection of hydrogen peroxide, where a high sensitivity of 0.04 μA μM -1 over a wide linear range of concentrations (16.6-990.1 μM) with a low detection limit (10.95 μM) was obtained for the fabricated sensors. All in all, this highly effective and simple strategy to improve the stability of Ag NWs will certainly open new avenues for their large-scale utilization in various electrochemical and sensing devices.

Background: In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with immunohistochemistry; compare with Pheochromacytoma of the Adrenal Gland Scaled Score (PASS) classification and analyse the differences between pheochromocytoma (Pheo), head-neck paragangliomas (HNPGL) and thoraco-abdominal-pelvic paraganglioma (TAPPGL) sub-groups., Methods: A total 114 PPGL cases (73 HNPGL, 15 TAPPGL and 27 Pheo belonging to 112 cases) are included. Immunohistochemically, SDHB and Ki-67 are investigated and malignancy risks are determined by PASS classification. Results are assessed statistically with chi-square test and p <0,01 is considered significant., Results: SDHB mutations are observed in 20 of 114 (17.54 %) PPGL cases, 3 (11,12%) of which is Pheo, 12 (16,44) is HNPGL, and 5 (35,71%) is TAPPGL (P <0,02). While 15/82 (18,29%) cases with SDHB mutations do not have a malignancy potential according to PASS classification, 5/32 (15,63%) cases has (p=0,73). TAPPGL, HNPGL and Pheo sub-groups have a significant difference between SDHB expression (p <0,02), malignancy potential according to PASS classification (p <0,0001) and Ki-67 proliferation index (p <0,0001)., Conclusion: To identify patients for molecular pathological examination, routine application of SDHB immunohistochemistry to PPGL tumors are suggested especially in HNPGLs.

Background: Ectopic adrenal tissue is a rare condition associated with embryological development defects seen in many different areas in the abdomen and pelvis. Here, we aimed to discuss the clinicopathological features of ectopic adrenal tissues diagnosed in our clinic, in light of the literature., Methods: We included cases of ectopic adrenal tissues incidentally detected in the specimens from patients undergoing operation for various diagnoses during 2012- March 2020. The cases were examined according to gender, age, location and accompanying pathological diagnoses. During this period, 15 cases of ectopic adrenal tissues (6 paratubal, 3 paraovarian, 2 paratesticular, 1 spermatic cord, 1 paraaortic, 1 liver capsule, 1 omentum) were detected accompanied by two endometrial carcinomas, two serous cystadenomas, one seminoma, one mixed germ cell tumor, one bilateral ovarian serous carcinoma and hepatic high-grade colon adenocarcinoma metastasis., Results: In this report, the fifth ectopic adrenal tissue accompanying a malignant testicular tumor, the fifth and sixth ectopic adrenal tissues occurring with ovarian serous cystadenoma, the first case observed with serous cystadenocarcinoma and the first case detected with hepatic adenocarcinoma metastasis are presented. Our cases are mostly women and adult men., Conclusion: Ectopic adrenal tissues can lead to hormonal problems and also to adrenal cortex and medulla neoplasms. Microscopically, they may be confused with clear cell gynecological and germ cell tumors. If the ectopic focus is misdiagnosed as an implant, a benign entity may be incorrectly reported as malignant. Also, it is important to prevent mis-staging in malignancies. For precise diagnosis, an immunopanel such as inhibin, melan A, and calretinin can be performed., (© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Copper nanowires (Cu NWs) hold promise as they possess equivalent intrinsic electrical conductivity and optical transparency to silver nanowires (Ag NWs) and cost substantially less. However, poor resistance to oxidation is the historical challenge that has prevented the large-scale industrial utilization of Cu NWs. Here, we use benzotriazole (BTA), an organic corrosion inhibitor, to passivate Cu NW networks. The stability of BTA-passivated networks under various environmental conditions was monitored and compared to that of bare Cu NW control samples. BTA passivation greatly enhanced the stability of networks without deteriorating their optoelectronic performance. Moreover, to demonstrate their potential, BTA-passivated networks were successfully utilized in the fabrication of a flexible capacitive tactile sensor. This passivation strategy has a strong potential to pave the way for large-scale utilization of Cu NW networks in optoelectronic devices.

Functional sequences of monodisperse, sequence-defined oligo(amide-urethane)s are designed based on a peptide sequence as blueprint. The translation of a discrete side-chain functionality sequence from a known peptide-based solubilizer of the photosensitizer meta-tetra(hydroxyphenyl)-chlorin, into a non-peptidic precision polymer backbone is demonstrated. The resulting peptidomimetic precision polymers retain the functions of the parent peptide sequence, showing analogues sensitivity toward single monomer mutations/exchanges and even exceeding the parent peptide equivalent by reaching up to 69% higher payload capacities and more favored release kinetics., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Functional sequences of precision polymers based on thiolactone/Michael chemistry are identified from a large one-bead one-compound library. Single-bead readout by MALDI-TOF MS/MS identifies sequences that host m-THPC that is a second generation photo-sensitizer drug. The corresponding Tla/Michael-PEG conjugates make m-THPC available in solution and drug payload as well as drug release kinetics can be fine-tuned by the precision segment., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: This study aims to evaluate the factors influencing the adequacy of endobronchial ultrasound-guided transbronchial fine needle aspiration specimens., Methods: A retrospective analysis of 1,700 endobronchial ultrasound-guided transbronchial fine needle aspiration samples obtained from 822 patients (500 males, 322 females; mean age 56±13 years; range 16 to 83 years) was performed between March 2011 and March 2014 at our center. Variables potentially associated with sampling adequacy, such as all cytological materials and procedure notes (lymph node and/or lesion size, localization, needle pass number, and slide number) were examined., Results: The overall specimen adequacy was 79.8%. The specimen adequacy was associated with needle pass number (p≤0.001). Adequacy rate was 66.9% for one needle pass and 85.8% for three needle passes. According to the sampling regions, adequacy rates showed a difference [69.2%-85.8%; (p≤0.005)]. In the multivariate logistic regression analysis of subcarinal (7) lymph node station, patient age (odds ratio, 0.983; 95% confidence interval, 0.966-1.000; p=0.049) and number of slides (odds ratio, 1.240; 95% confidence interval, 1.062-1.448; p=0.006) were independent determining factors of specimen adequacy. While independent determinants of specimen adequacy for the right paratracheal (4R) region were lymph node size (odds ratio, 1.486; 95% confidence interval, 0.973-2.268; p=0.067) and number of slides (odds ratio, 1.418; 95% confidence interval, 1.146-1.756; p=0.001), they were lymph node size (odds ratio, 1.594; 95% confidence interval, 0.960-2.645; p=0.071) and number of needle passes (odds ratio, 2.277; 95% confidence interval, 1.360-3.811; p=0.002) for the right interlobar (11R) region. Independent determinant of specimen adequacy for the left paratracheal (4L) lymph node station was the number of needle passes (odds ratio, 1.656; 95% confidence interval, 0.955-2.869; p=0.072)., Conclusion: During endobronchial ultrasound-guided transbronchial fine needle aspirations, particularly when rapid on site evaluation cannot be applied, consideration of factors affecting adequacy according to lymph node localizations may increase the chance for obtaining materials with suitable quality for cytologic evaluation., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2018, Turkish Society of Cardiovascular Surgery.)

A straightforward access route to multifunctional block copolymers, combining a poly(ethylene glycol) (PEG) block and a monodisperse segment with discrete monomer sequence based on thiolactone chemistry, is described. Exploiting an inverse conjugation strategy on a PEG preloaded poly(styrene) synthesis resin enables the convenient introduction of a predefined PEG-block at the α-terminus of thiolactone-based sequence-defined oligomers. Reaction conditions for the stepwise, submonomer synthesis at polar solid supports are optimized, using sequential synthesis on a model resin that enables to isolate and determine the purity of the oligomer segments by liquid chromatography-electrospray ionization mass spectrometry analysis. The reaction conditions are used to synthesize PEGylated 5mer precision polymers with defined monomer sequence in good yields and high purity to offer an interesting platform of macromolecules with potential for biomedical applications., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In many cancers, mast cell density (MCD) in the tumor microenvironment is associated with tumor progression and, to a greater extent, angiogenesis. Our study was designed to investigate the correlation between MCD, tumor lymphangiogenesis, and several well-established prognostic parameters in breast cancer. One hundred and four cases of invasive breast carcinoma diagnosed in our clinic between 2007 and 2011 were included. Mast cells and lymphatic vessels were stained with toluidine blue and D2-40, respectively, and their densities were calculated in various areas of tumors and lymph nodes. The variables of MCD and lymphatic vessel density (LVD) were compared using prognostic parameters as well as with each other. As tumor size and volume increased, MCD increased comparably in metastatic lymph nodes; intratumoral and peritumoral LVD also increased. Lymphovascular invasion, lymphatic invasion, perineural invasion, and estrogen receptor positivity were positively related to intratumoral MCD. The relationship between peritumoral MCD and nontumoral breast tissue MCD was statistically significant. Stage was correlated with MCD in metastatic lymph nodes. Metastatic lymph node MCD and intratumoral MCD were also significantly related. Stage, lymphatic invasion, perineural invasion, lymphovascular invasion, and metastatic lymph node MCD were all correlated with intratumoral and/or peritumoral LVD. As nuclear grade increased, intratumoral LVD became higher. In breast carcinoma, MCD, depending on its location, was related to several prognostic parameters. Notably, mast cells may have at least some effect on lymphangiogenesis, which appears to be a predictor of tumor progression., (Copyright © 2017. Published by Elsevier Taiwan.)

AB' type monomers containing a thiolactone unit and vinyl ether moiety have been prepared with high yields. Aminolysis of the thiolactone moiety generates the corresponding thiol in situ, and upon UV-irradiation, radical polyaddition occurs in the same medium, yielding linear poly(amide-urethane)s with different side chain residues and (Poly(Ethylene Oxide)) PEO-like backbone. Moreover, these unique polymers feature lower critical solution temperature behavior in water. Systematic modification of the responsive polymers reveals the influence of the variation of the side chains and the backbone structure on the corresponding solubility properties. In selected cases, multiresponsive polymers have been developed, which also respond to pH and metal concentration., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To describe a case of epithelioid trophoblastic tumor (ETT) in a postmenopausal woman, which had several peculiar features that differentiate it from previously reported ETTs., Case Report: ETT of the uterus is a rare form of trophoblastic tumor with only 100 cases distinguished until now. Our case differs from the previously reported ones due to its several exceptional features. Our patient had no history of trophoblastic or gynecological disease; is postmenopausal; had endocervical extension from the beginning; recurrences and metastasis at follow up; and had a high Ki-67 index and a normal beta-human chorionic gonadotropin value., Conclusion: Because precise differential diagnosis will alter the therapeutic approach and prognosis, it is necessary for treating physicians to be aware of these unusual presentations., (Copyright © 2015. Published by Elsevier B.V.)

Cyclooxygenase is an enzyme that changes the immune response to malign cells and catalyzes prostaglandins that may have an impact on cell proliferation. The purpose of this study was to examine the relation between established clinicopathological parameters in breast carcinomas and COX-2 protein expression. COX-2, estrogen receptor (ER), progesterone receptor (PR) and c-erB-2 primary antibodies were assessed in the slides prepared from the paraffin blocks of 62 invasive ductal carcinoma cases. The relation between ER, PR, and c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age were evaluated. The results were analyzed statistically. Cytoplasmic COX-2 expression was seen in 75.8% of all breast carcinomas. In both univariate and multivariate logistic regression analysis, there was a positive correlation between COX-2 expression and negative ER status, respectively (P=0.0173) (P=0.016). There was any statistically significant relation between PR positivity, c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age (P≥0.05). Given that there was found a statistically significant relation between COX-2 expression and negative ER status, which is considered a poor prognostic parameter, suggests that COX-2 expression can have a place among the other prognostic parameters of breast carcinoma.

Objective: Postoperative intraabdominal adhesions can be prevented by antibiotic lavage. We assessed whether systemic antibiotics could prevent adhesion formation in a rat model., Methods: Cecal abrasion was performed in the peritoneal cavities of 40 Wistar albino rats. Twenty rats were treated with a 5-day course of cefepim and metronidazole; the remaining animals were given saline injections. The animals were sacrificed 14 days after surgery. Adhesion severity scores and histopathologic findings were compared., Results: The median adhesion severity score was 2 (0-3) in the antibiotic group and 2.5 (1-4) in the controls (P = 0.03). In tissue specimens from controls, the adhesions were marked by mature collagen bundles. In treated rats, the adhesions were immature, characterized by early inflammatory cells, less collagen formation, and no collagen bundles., Conclusions: Postoperative systemic antibiotics slow adhesion formation and reduce the severity of the adhesions., (Copyright 2001 Academic Press.)