Il-6 and MSH3 in colorectal carcinoma: Expression, relationship, and prognostic significance in 171 colorectal carcinoma cases.

AIMS: Colorectal cancer (CRC), the most common type of gastrointestinal cancer, mostly develops as a result of environmental factors. Inflammation is a relatively uncommon but crucial contributor to its etiology, and inflammation is also thought to pose a risk in patients without a clinical diagnosis of inflammatory bowel disease. In cell lines, the proinflammatory cytokine interleukin-6 (IL-6) causes a cytosolic shift in the mismatch repair protein MSH3, accompanied by functional loss. This study aimed to evaluate IL-6 and MSH3 expression in 171 sporadic CRC samples by immunohistochemistry (IHC). High levels of IL-6 are hypothesized to cause MSH3 expression loss. We also explored the clinical/pathological aspects of IHC-detected MSH3 loss and the relationship between MSH3 expression and tumor-infiltrating lymphocytes (TILs). MATERIALS AND METHODS: IL-6 and MSH3 IHC and H and E slides were evaluated by two pathologists. Clinical data were obtained from the institution's database. RESULTS: A relationship between MSH3 loss and IL-6 expression was not proven (P = 0.963). MSH3 staining was significantly reduced in the patient group with high TILs (P = 0.035). We observed 104 CRC cases (60.8%) with IL-6 expression and 85 cases (49.7%) with reduced MSH3 expression. CONCLUSION: This study did not demonstrate an association between IL-6 and MSH3 expression. As MSH3 is a relatively little-known protein, further large-scale studies are needed. The use of IHC to identify patients who may benefit from anti-IL-6 therapies in CRC in the future may be critical.

Immunohistochemical Approach to Mismatch Repair Deficiency in Pediatric High-Grade Glioma.

Knowledge of the molecular pathways of pediatric high-grade gliomas is increasing. Gliomas with mismatch repair deficiency do not currently comprise a distinct group, but data on this topic have been accumulating in recent publications. Immunohistochemistry can effectively determine mismatch repair status, indirectly suggesting the microsatellite instability of the tumor. This study aimed to determine the number of mismatch repair-deficient pediatric high-grade gliomas in a tertiary institution and assess the relationship between the survival and mismatch repair status of the patients. It also aimed to assess the potential for further clinical studies including immunotherapy. Of 24 patients with high-grade gliomas, 3 deceased patients were mismatch repair-deficient. Mismatch repair deficiency was significantly associated with shorter survival (P=0.004). Immunotherapy trials need to progress, and patients with mismatch repair-deficient pediatric high-grade gliomas are the most suitable candidates for such studies.

Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.

Evaluation of endometrial receptivity in recurrent pregnancy loss and recurrent implantation failure.

Objective: The cause of implantation defects in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) has not been clearly established. We aimed to evaluate the immunohistochemical changes in HOXA-11, ß1 integrin, focal adhesion kinase (FAK), cluster of differentiation 44 (CD44), and extracellular matrix protein 1 (ECM1) molecules during the receptive endometrial period in patients with RIF and RPL. Materials and Methods: This study was retrospectively conducted at a university hospital. After the exclusion of cases with pathology that may cause a change in the level of receptors in the endometrium, biopsies performed during the receptive period were selected, and the patients were categorized into RPL (n=15), RIF (n=16), control (n=16) groups. All preparations were immunohistochemically stained for HOXA-11, ß1 integrin, FAK, CD44, and ECM1. Results: HOXA-11 and ß1 Integrin expression changes were similar between the RIF and control groups. However, FAK expression was significantly increased in the RIF group (p<0.01). Additionally, ECM1 and CD44 expressions were significantly decreased in the RIF group compared with the control group (p<0.01). There was no significant difference in the endometrial staining of HOXA-11, FAK, and ECM1 in patients with a history of RPL. However, ß1 Integrin and CD44 levels were significantly decreased in the RPL group compared with the control group (p<0.05). Conclusion: Implantation is a complex process, and altered adhesion mechanisms involved in endometrial receptivity may be related to defective implantation in patients with RIF and RPL. Among the adhesion molecules, the expression of CD44, ß1 integrin, FAK, and ECM1 molecules varies in inappropriate implantation compared with the normal population.

Retrospective Analysis of Paediatric Glial Tumours that Required Modern Molecular Techniques.

AIM: To determine if previous histological grading systems were sufficient or unreliable with a limited repository of modern techniques. MATERIAL AND METHODS: The pathology reports of pediatric neurosurgery patients between 2019-2022 were accessed. Data on patients that needed unattainable further molecular investigation were extracted. Data were noted from electronic archives, including their sex, age, histologic grade, location, resection type, survival, and therapy. RESULTS: Out of 61 surgeries, 17 patients needed further investigation for a proper 2022 World Health Organization (WHO) diagnosis. Seven were deceased, and nine were alive. Two of 10 patients with low-grade gliomas and five of six patients with highgrade gliomas were deceased. Data on one foreign patient with high-grade glioma was inaccessible. The average survival was 9 months for the deceased. CONCLUSION: Modern molecular techniques such as next-generation sequencing and methylation profiling are the state-ofthe- art methods, but it is hard for developing and underdeveloped countries to utilize such methods. The classification schemes, diagnostic key figures, and treatment modalities are developed using these techniques, but the less developed world is incapable of achieving these. We are trying to hybridize the modern and classic modalities, and the results of our study show that for overall survival, there is still not much difference. More economic and feasible techniques should be produced and summarized for the rest of the world.

Histopathologic Features for Overall Survival in Merkel Cell Carcinoma: A Case Series with Intact Mismatch Repair Protein Expression.

OBJECTIVE: In a study of Merkel cell carcinoma (MCC), a fusion transcript between MLH1 and SPATA4 was identified. This fusion has the potential to generate the inactive or dominant-negative form of the protein. Therefore, we aimed to investigate whether mismatch repair protein deficiency occurr in MCC cases or not, in addition to the overall survival association with histopathologic features. MATERIAL AND METHOD: A retrospective review of 15 patients diagnosed with a biopsy-proven Merkel Cell Carcinoma between 2012 and 2019 was performed. Mismatch repair (MMR) protein expressions were evaluated by immunohistochemistry. RESULTS: The median follow-up time was 36 months (mean 41, range 2-103 months). Six (40%) patients died during follow-up. The overall survival (OS) at 1 year, 2 years, 3 years, and 5 years were 87%, 80%, 62%, and 53%, respectively. The patients diagnosed at < 60 years had an improved OS compared to those ≥60 years of age (p=0.016). Patients in clinical stage I had better OS than patients in clinical stage IV (p=0.011). Cases with pathological tumor stage (pT) 1 had better OS than pT3 and pT4 (p=0.045). Adjuvant radiotherapy or adjuvant radiotherapy+chemotherapy treatment improved OS compared to adjuvant chemotherapy (p=0.003). MMR protein nuclear expression was intact in 12 cases available for immunohistochemical study. CONCLUSION: To the best of our knowledge, this is the second study that preferentially investigated the mismatch repair protein status of Merkel Cell Carcinoma. No mismatch repair protein deficiency of MCC cases was identified in the current study.

Association of Merkel Cell Polyomavirus Status With p53, RB1, and PD-L1 Expression and Patient Prognosis in Merkel Cell Carcinomas: Clinical, Morphologic, and Immunohistochemical Evaluation of 17 Cases.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, primary neuroendocrine carcinoma of the skin whose main risk factors are immunosuppression, UV radiation exposure, and Merkel cell polyomavirus. Programmed death-1/programmed death ligand-1 (PD-L1)-based immunotherapy is currently the first choice for treating patients with metastatic MCC. METHODS: MCC biopsies (17) were evaluated for their nucleus and cytoplasm characteristics and growth patterns, as well as for intratumor lymphocytes, mitotic number, and lymphovascular invasion. Paraffin-embedded tissue samples of the biopsies were stained with MCPyV large T-antigen (LTag), RB1, p53, and PD-L1. RESULTS: We observed MCPyV LTag expression in 9 out of the 17 tumors, and all 9 cases were positive for RB1 ( P <0.000). p53 staining was not significantly correlated with MCPyV LTag. We observed no relationship between p53 expression and any other parameters, and PD-L1 expression was low in the MCC samples. We evaluated PD-L1 using both the combined positive score and tumor proportion score (TPS), and found that TPS was correlated with MCPyV LTag expression ( P =0.016). Tumors with tumor-infiltrating lymphocytes showed a better prognosis than those without these lymphocytes ( P =0.006). DISCUSSION: Our data demonstrated that RB1 was effective for immunohistochemically investigating the MCPyV status of tumors. TPS was superior to the combined positive score in evaluating PD-L1 in MCC. Tumor-infiltrating lymphocytes were the only parameters that were associated with survival. Further studies with larger series are required to confirm these results.

The Utility of Quantitative Parameters of Shear-Wave Elastography to Predict Prognostic Histologic Features of Breast Cancer.

ABSTRACT: In this study, we aimed to investigate the correlation of stiffness values of shear-wave elastography (SWE) and histopathological prognostic factors in patients with breast cancer. Between January 2021 and June 2022, SWE images of 138 core-biopsy proven breast cancer lesions from 132 patients were retrospectively reviewed. Histopathogic prognostic factors, including tumor size, histologic grade, histologic type, hormone receptor positivity, human epidermal growth factor receptor (HER2) status, immunohistochemical subtype and Ki-67 index were documented. Elasticity values including mean and maximum elasticity ( Emean and Emax ) and lesion-to-fat ratio ( Eratio ) were recorded. The association between histopathological prognostic factors and elasticity values were assessed using Mann-Whitney U and Kruskal-Wallis test, and multiple linear regression analysis. Tumor size, histological grade, and Ki-67 index were significantly associated with the Eratio ( P < 0.05). Larger tumor size and higher Ki-67 index also showed significantly higher Emean and Emax values ( P < 0.05). However, hormone receptor positivity, HER2 status, and immunohistochemical subtype were not significantly associated with elasticity values ( P > 0.05). Multivariate logistic regression analysis revealed that tumor size was significantly associated with Emean , Emax , and Eratio values ( P < 0.05). A high Ki-67 index was also significantly associated with high Eratio values. Larger tumor size and higher Ki-67 index are independently associated with high Eratio values. Preoperative SWE may improve the performance of conventional ultrasound in predicting prognosis and treatment planning.

Which one is better for predicting extraprostatic extension on multiparametric MRI: ESUR score, Likert scale, tumor contact length, or EPE grade?

PURPOSE: To evaluate the European Society of Urogenital Radiology (ESUR) score, the Likert scale, tumor contact length (TCL) > 1 cm, and EPE (extraprostatic extension) grade in predicting EPE at multiparametric magnetic resonance imaging (mp-MRI). METHODS: Seventy-nine patients who underwent 3-T MRI and were histopathologically confirmed by microblocks were enrolled in this retrospective study. The index lesions were interpreted by two experienced radiologists. Apparent diffusion coefficient (ADC) values were also noted. Weighted κ statistics were used to compare interreader agreement. Univariate logistic regression analysis was performed to define independent predictors of EPE status. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to compare the MRI-based methods and clinical variables (ISUP grade, prostate volume and PSA density) + MRI-based methods for pathologic EPE prediction by using the area under the curve (AUC) value. RESULTS: The mean age was 64.5 years ± 6.2. 33/79 (41.8%) patients had pathologic EPE. As ESUR score showed weak interreader agreement (κ = 0.537), Likert scale, TCL, and EPE grade showed moderate agreement (κ = 0.608, κ = 0.747, κ = 0.647 respectively). Univariate ROC analysis result showed that all MRI-based score systems, mean ADC value, the ISUP grade, prostate volume, PSA density were the best variables in predicting EPE. ROC analysis results of four MRI-based methods showed good diagnostic performance. At multivariate analysis, all clinical models showed excellent diagnostic performance. CONCLUSION: All four MRI-based methods had good diagnostic performance. Furthermore, consisting of both qualitative and quantitative parameters and being less reader experience dependent, EPE grade was a promising method in predicting EPE. All clinical models showed excellent diagnostic performance.

The Histopathological Effect of Aloe Vera on the Wound Healing Process in a Surgically Created Tubularized Incised Plate Urethroplasty Model on Rats.

BACKGROUND: Hypospadias is a common congenital anomaly which is determined as an abnormal urethral opening on the ventral face of penis. The purpose of this rat model study was to research the effect of topically applied Aloe vera after a tubularized incised plate urethroplasty (TIPU). METHODS: The TIPU model was applied to male Wistar albino rats. A total of 30 rats were randomly grouped into 3 groups of 10. Group I was assigned as the control group, treated with 0.9% saline only twice a day for 15 days. Group II received topical Aloe vera gel once a day and Group III received Aloe vera gel twice a day. Spongiofibrosis was graded as 0: none, 1+:≤10% tissues involved, 2+:10%-49% tissues involved, 3+: ≥ 50% tissues involved. RESULTS: A higher degree of fibrosis and inflammation was determined in the Group I subjects than in Groups II and III. Fibrosis of grade 3+ was observed in 33% of the control group and not in any of the two Aloe groups (p = 0.043). Inflammation of grade 3+ was seen in 66.7% of the control group, in 10% of Group II, and in 33% of Group III (p = 0.02). CONCLUSIONS: The topical application of Aloe vera to a surgically created tubularized incised plate urethroplasty model decreased inflammation and fibrosis that may affect the success rates of this operation.

Comparison of the effects of operating microscopes with light emitting diode and halogen light source on the eye: a rabbit study.

PURPOSE: To evaluate the potential toxicity of operation microscopes with halogen and light emitting diode (LED) light source on the rabbit eyes. MATERIALS AND METHODS: Thirty-two eyes of 16 male New Zealand pigmented rabbits were involved in the study. The rabbits were divided into two groups according to the type of light source applied. Only one eye of each rabbit was exposed to illumination light, unexposed fellow eyes served as the control group. Experimental groups included group 1 exposed to halogen light for 2 h and evaluated 1 day and 1 week after the illumination, group 2 exposed to LED light for two hours and evaluated 1 day and 1 week after the illumination. On the first and seventh days after exposing the light, we evaluated the rabbit corneas using in vivo confocal microscopy (IVCM). At the end of the seventh day, the Hematoxylin-eosin staining and TUNEL staining were performed to investigate the presence of apoptosis in the retina and retina pigment epithelium. RESULTS: Early IVCM findings revealed corneal epithelial cell ovalization and indistinct intercellular borders in the halogen light group. We also observed more increase in the keratocyte density index (23.7% vs 14.1%, p = 0.001, respectively) and the Bowman reflectivity index (12.4% vs 4.1%, p = 0.001, respectively) at first day of the light exposure in halogen light group compared to LED light group. However, late IVCM indicated that these findings disappeared one week later. No apoptosis was observed in the corneal and retinal layers in early and late examination groups. CONCLUSION: The present experimental study demonstrated that both halogen and LED lights, which were commonly used for microscopic eye surgery, had no sustained adverse effect on the cornea and retina of the rabbits; however, halogen light had a temporary adverse effect on corneal epithelium and stroma, which resolved within 1 week.

Effects of chronic sleep deprivation on upper respiratory tract mucosal histology and mucociliary clearance on rats.

In this study, we aimed to investigate the effects of chronic sleep deprivation on mucociliary clearance, which is the primary defence mechanism of the upper airway tract and nasal mucosal histology. Forty-two Wistar Albino rats (250-300 g), 8 or 12 weeks old, were randomly assigned into three groups as follows. The first sleep-deprivation group consisted of 14 rats (A), another 14 of them were assigned to platform group (B), and the remaining 14 were included to the home cage control group (C). For the two deprivation groups (A and B), the modified multiple platform method (MMPM) was used to induce sleep deprivation for 21 days. Tc-99m MAA rhinoscintigraphy was performed to assess mucociliary clearance and the nasal histopathological changes of the sacrificed rats were also examined. Mucociliary clearance was significantly higher in sleep deprivation (A) and deprivation control (B) groups than the control group (C) (p = .037). The ratio of columnar ciliary was significantly higher in group A and B than in the control group (p = .003). The transitional epithelial ratio in groups A and B was also significantly increased compared with group C (p = .04). The control group's squamous epithelial ratio was increased compared to the sleep-deprived groups (p = .003). There was a significantly increased inflammatory response in the ciliated columnar epithelium in groups A and B compared to group C (p = .02). For the first time in the literature, we demonstrated that chronic sleep deprivation has caused a significant increase in mucociliary clearance speed and in the number of ciliary cells.