Morphomolecular Correlation and Clinicopathologic Analysis in Endometrial Carcinoma.

Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140-125.606, P=0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.

Investigation of YAP-1, OTX-2, and nestin protein expressions in neuroblastoma: a preliminary study.

OBJECTIVES: Neuroblastoma is the most common extracranial solid tumor in childhood. YAP (Yes-associated protein) is a highly expressed protein in NB. Nestin is an important marker of neuronal differentiation in NB. Orthodenticle homeobox (OTX) is a transcription factor and is overexpressed in blastoma-derived tumors. The aim of this study was to examine the potential roles of YAP-1, Nestin, and OTX-2 proteins in prognosis and risk stratification in neuroblastoma METHODS: Tumor sections of 56 patients with different NB risk groups were analyzed. YAP-1, Nestin, and OTX-2 protein expression levels were evaluated by immunohistochemical staining in NB patient tissue samples. RESULTS: YAP-1, Nestin, and OTX-2 protein expression levels were evaluated together with the clinical findings of NB patients. YAP-1 was expressed in 18% of all tissues, while Nestin was expressed in 20.4%. OTX-2 protein expression was found in 41.1% of the NB patients. YAP-1 was expressed in 26.9% of high-risk and 11.5% of low-risk patients. Nestin was expressed in 24.4% high-risk and 33.3% low-risk patients. OTX-2 was expressed in 68.2% high-risk and 60% low-risk patients.YAP-1 was shown to provide survival advantages among risk groups. INTERPRETATION: The findings of this study support that YAP-1 may be a potential prognostic biomarker for staging and risk-group assignment of NB patients. YAP-1 expression in neuroblastoma is associated with significantly poorer survival probabilities and should be considered as a potential therapeutic target. OTX-2 is a promising predictive biomarker candidate, but its mechanisms need further investigation in neuroblastoma, as nestin expression is not significantly linked to patient survival.

The prognostic significance of PD-1 and its ligands in non-small cell lung cancer.

Background: In this study, we aimed to investigate the prognostic value of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and programmed cell death ligand 2 (PD-L2) expressions on immune and cancer cells in terms of survival in patients with lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Methods: Between January 2000 and December 2012, a total of 191 patients (172 males, 19 females; mean age: 60.3±8.4 years; range, 38 to 78 years) who were diagnosed with non-small cell lung cancer and underwent anatomic resection and mediastinal lymph node dissection were retrospectively analyzed. The patients were evaluated in three groups including lung squamous cell carcinoma (n=61), adenocarcinoma (n=66), and large-cell carcinoma (n=64). The survival rates of all three groups were compared in terms of immunohistochemical expression levels of PD-1, PD-L1, and PD-L2. Results: The mean follow-up was 71.8±47.9 months. In all histological subtypes, PD-1 expressions on tumor and immune cells were observed in 33% (61/191) and in 53.1% (102/191) of the patients, respectively. Higher expression levels of PD-L1 and PD-L2 at any intensity on tumor and immune cells were defined only in lung adenocarcinomas, and PD-L1 and PD-L2 values were detected in 36.4% (22/64) of these patients. The PD-L1 expressions on tumor and immune cells were observed in 41.7% (10/24) and 25% (6/24) of the patients, respectively. The PD-L2 expressions on tumor and immune cells were detected in 16.7% (4/24) and 8.4% (2/24) of the patients, respectively. Univariate and multivariate analyses revealed that PD-1 expression in tumor cells was an independent prognostic factor in all histological subtypes. Conclusion: Our study results suggest that PD-1 expression is a poor prognostic factor for overall survival in patients with completely resected adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

lncRNA XIST Interacts with Regulatory T Cells within the Tumor Microenvironment in Chronic Hepatitis B-Associated Hepatocellular Carcinoma.

OBJECTIVE: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment. MATERIAL AND METHODS: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed. RESULTS: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19). CONCLUSION: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

S-100 and MATH-1 Protein Expressions Can Be Useful for the Prediction of Clinical Outcome in Neuroblastoma Patients.

Neuroblastoma (NB) is the most frequent extracranial solid tumor of childhood, remarkable for its broad spectrum of clinical behavior. This diversity in behavior correlates closely with defined clinical and biological features and combinations of prognostic variables are used for risk-group assignment. S-100 proteins have roles in differentiation and were shown to be frequently dysregulated in NB. MATH-1 protein plays role in neuronal cell differentiation through development. However, up to date, there are no studies evaluating the relationship between MATH-1 and NB. Grb2-associated binding (Gab) proteins have roles in the regulation of cell growth and differentiation. Gab1 was reported to be related to poor survival of high-risk NB patients. The aim of this study was to investigate the relationship between differentiation-related S-100, MATH-1, and Gab1 proteins and risk group and/or stages of NB. A significant relation was found between S-100 and early stages of NB. This study also revealed a significant association between MATH-1 and low-risk groups. S-100 and MATH-1 were also shown to provide survival advantages among stages and risk groups. The findings of this study support the assumption that S-100 and MATH-1 can be potential prognostic biomarkers for staging and risk-group assignment of NB patients. These proteins can be useful tools for clinicians to guide through treatment options, especially for the evaluation of tumor differentiation.

Identification of ALK Mutation in Neuroblastoma on the Point of Molecular Heterogeneity.

BACKGROUND AND AIM: In neuroblastoma, anaplastic lymphoma kinase mutations have recently received attention as molecular targets for the treatment of neuroblastoma, as 6% to 10% of patients with neuroblastoma have anaplastic lymphoma kinase mutations. There are little data from the cases in Turkey. We aimed to detect anaplastic lymphoma kinase mutations and molecular heterogeneity in neuroblastoma using next-generation sequencing. This study is the first one with this many cases in Turkey. METHODS: Next-generation sequencing analysis was performed using an Illumina MiniSeq custom gene panel. Clinically important mutations were selected for the analysis. We also gathered clinical data of the patients from Turkish Pediatric Oncology Group cohorts to associate them with anaplastic lymphoma kinase mutations. This study is a retrospective cross-sectional study. We followed STROBE guideline (https://www.equator-network.org/reporting-guidelines/strobe/) on this study. RESULTS: We analyzed anaplastic lymphoma kinase in 108 patients with neuroblastoma, with a mean age of 43.76 months. Pathogenic anaplastic lymphoma kinase mutations were detected in 13 patients (12.04%). We noted that anaplastic lymphoma kinase mutations were primarily observed in intermediate- and high-risk patients (P = .028). R1275Q and F1174-related mutations were predominant; I1171T, L1226F, S1189F, V1135A, and G1125S mutations were rare. Duplicate samples did not exhibit any heterogeneity. CONCLUSIONS: We found that F1174 and R1275Q-related anaplastic lymphoma kinase mutations are the most common pathogenic mutations in neuroblastoma. Anaplastic lymphoma kinase mutation status did not show any heterogeneity, and the mutations were correlated with intermediate- or high-risk groups.

Genomic Alterations of Signaling and DNA Damage Repair Pathways in Non-Muscle Invasive Bladder Cancer.

The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.

Comparing Tribbles Homolog 3 (TRIB3) Protein Expression Levels with Clinicopathological Characteristics and Survival Among Neuroblastoma Patients.

Background: Tribbles Homolog 3 (TRIB3) is a member of the pseudokinase family of tribbles and acts as an adaptor protein to regulate different cellular processes. Upregulation of TRIB3 expression was shown either as a favorable or an adverse prognostic factor in various adult malignancies. However, TRIB3 expression has not been examined in pediatric cancers. Neuroblastoma is the most common malignant solid tumor of childhood, which affects mostly children under 5 years old. Risk stratification of patients defined by International Neuroblastoma Risk Group was used to determine prognosis and treatment of the disease. This study aimed to examine the relationship between TRIB3 protein expression levels and clinicopathological features and survival of patients. Methods: TRIB3 protein expression was analyzed using immunohistochemical staining on formalin-fixed paraffin-embedded tissue samples of neuroblastoma patients (n = 56). Survival analyses were performed with Kaplan-Meier method and log-rank tests. Association between TRIB3 expression and clinicopathological characteristics were analyzed with Spearman's correlation. Results: Of the patients, 32.1% were in the low-risk group, 21.4% in the medium-risk group, and 46.4% in the high-risk group. Survival analysis was performed in the entire neuroblastoma patient group and sub-risk groups of neuroblastoma patients. In the entire patient group, there was no significant difference in overall survival (P = .202) and event-free survival (P = .172) between TRIB3-positive and -negative patients. However, when survival analyses were performed in each risk group, TRIB3 expression was significantly associated with higher overall survival (P = .034) and event-free survival (P = .032) in low-risk group neuroblastoma patients. Nevertheless, no association was found between TRIB3 expression and overall survival (P = .799) and event-free survival (P = .448) in high-risk neuroblastoma patients. Furthermore, a significant correlation was identified between 1p36 loss-of-heterozygosity and TRIB3 expression (P = .030). However, TRIB3 expression did not correlate with other clinicopathological features. Conclusion: TRIB3 expression is a potential predictive biomarker for low-risk neuroblastoma patients.

Investigation of the effectiveness of hyperthermic intraperitoneal chemotherapy in experimental colorectal peritoneal metastasis model.

Objectives: In our study, we aimed to (1) create a peritoneal metastasis (PM) model in nude mice, administer intraperitoneal chemotherapy using the peritoneal infusion pump we developed in this model, and (2) compare the efficacy of intraperitoneal chemotherapy using various drugs at different temperatures. Methods: The peritoneal metastasis model was established in nude mice using the CC531 colon carcinoma cell line. Models with peritoneal metastasis (PM) were randomized into four groups of seven animals each: Group 1, control group (n=7); Group 2, normothermic intraperitoneal chemotherapy (NIPEC) with mitomycin C(MMC) (n=7); Group 3, hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (n=7), and Group 4, NIPEC with 5-fluorouracil (5-FU). Results: Tumor development was achieved in all animals. While the tumor burden decreased significantly in the treatment Group 3 (p=0.034), no significant difference was found in the other groups. In the PM mouse model, hyperthermic intraperitoneal administration of MMC had the highest tumoricidal effect. Conclusions: Our PM model provided a good opportunity to examine the efficacy of HIPEC and intraperitoneal infusion pump (IPIP). In future studies, we plan to evaluate efficacies of different drugs in the PM models we have created.

Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies.

BACKGROUND: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of the present study was to document the specific gene mutations related to targeted therapy in relapsed or refractory NB patients by using next generation sequencing (NGS). METHODS: The study included 57 NB patients from amongst 1965 neuroblastic cases in Turkey who experienced a recurrence after multi-model therapy. The cases were diagnosed, risk-stratified, and treated according to the classification system from the International Neuroblastoma Risk Group. Single nucleotide variations in 60 genes were investigated using the Pillar Onco/Reveal Multicancer v4 panel and Pillar RNA fusion panel on the Illumina Miniseq platform. RESULTS: ERBB2 I655V was the most frequent mutation and was found in 39.65% of cases. Anaplastic Lymphoma Kinase (ALK) mutations (F1174L, R1275Q, and rare mutations in the tyrosine kinase domain) were detected in 29.3% of cases. Fusion mutations in NTRK1, NTRK3, ROS1, RET, FGFR3, ALK and BRAF were observed in 19.6% of cases. CONCLUSIONS: This study presents valuable mutation data for relapsed and refractory NB patients. The high frequency of the ERBB2 I655V mutation may allow further exploration of this mutation as a potential therapeutic target. Rare BRAF mutations may also provide opportunities for targeted therapy. The role of ABL1 mutations in NB should also be explored further.

Synthesis and Optimization of the Docetaxel-Loaded and Durvalumab-Targeted Human Serum Albumin Nanoparticles, In Vitro Characterization on Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) tends to behave more aggressively compared to other breast cancer subtypes due to the lack of receptors and its limited targeting therapy. In recent years, nanotechnology advancement has led to the development of various nanoparticle platforms for the targeted treatment of cancers. Especially, HSA-NPs have specific advantages such as biocompatibility, adjustable size during production, and relatively easy synthesis. In this study, HSA-NPs were encapsulated with docetaxel (DTX) and functionalized with polyethylene glycol (PEG), also becoming a targeting nanoplatform modified with durvalumab (DVL), and the whole nanostructure was well characterized. Subsequently, drug release studies and various in vitro cell culture studies such as determining the cytotoxicity and apoptotic levels of the nanoplatforms and PD-L1 using ELISA test were conducted on MDA-MB-468, MDA-MB-231, and MCF-7 cells. According to the results, HSA-DTX@PEG-DVL NPs showed better cytotoxicity compared to DTX in all the three cell lines. In addition, it was observed that the HSA-DTX@PEG-DVL NPs did not lead the cells to late apoptosis but were effective in the early apoptotic stage. Moreover, the ELISA data showed a significantly induced PD-L1 expression due to the presence of DVL in the nanostructure, which indicates that DVL antibodies successfully bind to the HSA-DTX@PEG-DVL nanostructure.

The prognostic role of epidermal growth factor receptor mutation in completely resected ampullary adenocarcinoma.

The aim of this study is to make a differential diagnosis and prognosis of the ampullary adenocarcinoma subtypes. We also investigated the role of prognostic markers PD-1 and PD-L1, and epidermal growth factor receptor (EGFR). Local or locally advanced stage ampullary adenocarcinoma patients who had undergone pancreaticoduodenectomy at the time of diagnosis were included. MUC1, MUC2, MUC5AC, CDX2, CK7, CK20, PD-1, and PDL-1 were analysed immunohistochemically, and EGFR was analysed by real-time polymerase chain reaction. According to histopathological and immunohistochemical evaluation, we found 27 patients as pancreatobiliary type and 56 patients as intestinal type adenocarcinoma. The median survival of patients with intestinal and pancreatobiliary type adenocarcinoma was 23 months and 76 months ( p = 0.201), respectively. When the survival of PD1-positive ( n = 23) and PD-L1-positive ( n = 18) patients were compared with the patients with negative staining ( n = 60, n = 65), no significant difference was found. Epidermal growth factor receptor mutation was detected in a total of 6 patients, and 5 of these 6 mutations were shown in intestinal type tumours and one in a pancreatobiliary type tumour. A significant difference was determined in terms of overall survival for the patients with EGFR mutations compared to those without ( p = 0.008). In conclusion, we could reveal the prognostic significance of EGFR mutation, which is also a target molecule.

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

Aim: To evaluate the ex vivo efficacy of chemotherapy, immunotherapy and targeted agents with the oncogram method in patients with bladder cancer and determine the most appropriate personalized treatment agent using immune markers. Materials & methods: Bladder cancer tissues were obtained from each patient. After cultivation, cell cultures were divided into 12 groups for each patient and 11 drugs were administered. Cell viability and immunohistochemistry expression were examined. Results: A good response rate was determined to be a 23% viability drop. The nivolumab good response rate was slightly better in PD-L1-positive patients and the ipilimumab good response rate was slightly better in tumoral CTLA-4-positive cases. Interestingly, the cetuximab response was worse in EGFR-positive cases. Conclusion: Although good responses of drug groups after their ex vivo application by using oncogram were found to be higher than control group, this outcome differed on a per patient basis.

Bladder cancer primary cell cultures were shown to be effective for drug sensitivity and also able to be used ex vivo in the process of determining personalized treatment. The ex vivo efficacy of 11 different agents was evaluated with oncogram in bladder cancer cell cultures obtained from patients. Together with clinicopathological features, evaluation of drug responses detected by oncogram can provide important information for pretreatment drug selection when deciding on individualized treatment.

Whole-exome sequencing reveals genetic variants in low-risk and high-risk neuroblastoma.

This study aimed to investigate the genetic aberrations in neuroblastoma (NB) by comparing high and low-risk NB patients by whole-exome sequencing (WES) and to reveal the heterogeneity and association between somatic variants and clinical features. Seven NB patients with available clinical data were included in the study (4 in the low-risk group and 3 in the high-risk group). WES was performed and somatic variants associated with NB genes in the COSMIC database were selected through bioinformatics pipeline analysis. Variants were determined using the Integrative Genomics Viewer (IGV). Some gene variations were found in both groups, including variations in oncogene and tumor suppressor genes. In general, candidate gene variations were associated with chromatin remodeling complexes, the RAS pathway, cell proliferation, and DNA repair mechanism. Some variations in CSF1R, MSH6, PTPN11, SOX9, RET, TSC1, and DNMT1 genes were detected only in high-risk patients, while EP300, TET2, MYCN, PRDM1, and ARID2 gene variations were detected only in low-risk patients. When high-risk gene variants were compared with the cBioportal cancer genomic database, two common gene variants (ARID1A and NCOR2) were identified. However, when low-risk gene variants were compared with the cBioportal cancer genomic database, no common genes were found. GO/KEGG enrichment analysis was performed to find relevant biological processes and molecular pathways related to gene variants, which will help to decipher the molecular mechanisms of NB tumorigenesis and the phenotypic differences between high-risk and low-risk patients.

Erratum to: Evaluation of gene expression levels in the diagnosis of lung adenocarcinoma and malignant pleural mesothelioma.

[This corrects the article DOI: 10.5606/tgkdc.dergisi.2020.17279.].

The Effect of Bevacizumab and Propranolol on Nasal Polyposis.

Objective: This study aims to evaluate the effects of bevacizumab and propranolol from the point of view of a possible antiangiogenic effect in a model of primary nasal polyp (NP) tissue culture. Methods: NP samples of 21 patients and normal healthy nasal mucosa samples of 7 patients were cultured. Samples were divided into four groups as follows (healthy nasal mucosa, NP without any treatment, NP treated with propranolol, NP treated with bevacizumab). Cultured tissues were formalin fixed and paraffin embedded. Tissue sections and immunohistochemical VEGF-A, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) expressions were evaluated. ELISA was also performed for each one of them. Results: Both propranolol and bevacizumab significantly decreased the expressions of VEGF-A and Ang-1, and they significantly increased the expression of Ang-2 in comparison to the control NP group. In the healthy nasal mucosa group, no significant expression of VEGF-A was seen, a slight (+) Ang-1 expression, and a high (+++) Ang-2 expression were observed. Conclusion: Bevacizumab and propranolol exert an antiangiogenic effect on NP tissues, mainly by decreasing VEGF-A and Ang-1 expression, increasing Ang-2 expression.

Comparison of Cytotoxic and Ototoxic Effects of Lipoplatin and Cisplatin in Neuroblastoma In Vivo Tumor Model.

BACKGROUND: This study aimed to compare the cytotoxic, cytostatic, and ototoxic effects of lipoplatin compared to cisplatin application in the subcutaneous xenograft nude mouse neuroblastoma tumor model. METHODS: In this study, C1300 neuroblastoma cells were administered subcutaneously to 21 male nude mice. When the tumor reached 150 mm3 diameter, mice were randomized into 3 groups. Saline, cisplatin, and lipoplatin were given intraperitoneally. The auditory function tests were performed before administration and 72 hours after administration. Mice were sacrificed and the tumor and cochlea were removed after 72 hours. Histopathologic evaluation of necrosis and apoptosis was determined by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Cyclooxygenase 2, superoxide dismutase 2, and inducible nitric oxide synthase levels were determined by immunohistochemistry in tissue samples. RESULTS: Apoptosis and necrosis rates were higher in lipoplatin group than in cisplatin group (P=.035 and P=.010, respectively) in tumor tissue. In the spiral ganglion, apoptosis and necrosis were lower in the lipoplatin group than in cisplatin group (P=.002 and P=.002, respectively). Cyclooxygenase 2 pattern in the cochlea was positive in both control and lipoplatin group and negative in cisplatin group (P=.001). Superoxide dismutase 2 and inducible nitric oxide synthase 2 protein expressions showed no difference between groups. The auditory functions were similar to baseline values and had a better threshold value in lipoplatin group than cisplatin group. CONCLUSION: For the treatment of neuroblastoma, the use of lipoplatin seems to be beneficial in reducing side effects of cisplatin. We recommend that the mechanism of these properties of lipoplatin should be evaluated in further studies.

Association of immune response with overall and disease-free survival in laryngeal squamous cell carcinomas.

OBJECTIVES: This study aimed to examine the relationship between checkpoint receptors (PD-1, PD-L1, PD-L2, CTLA-4) and lymphoid infiltration level (TILs) with prognostic features of patients with laryngeal squamous cell carcinoma (LSCC). METHODS: A retrospective study was designed at a tertiary referential university hospital between April 2008 and December 2020. The surgical specimen of the patients who met the eligibility criteria were re-examined histopathological, sociodemographic, clinical, pathological, and follow-up findings of patients were determined. The impact of PD-1, PD-L1, PD-L2, CTLA4, and TILs levels for the presence of cancer recurrence, disease-specific mortality, overall survival (OS), disease-free survival (DFS) was investigated. RESULTS: Forty-five patients with LSCC were included in the study. The mean follow-up period was 48.3 ± 14.3 months (min: 36, max 84). TILs scores were detected significantly lower in patients with distant metastasis and recurrence (p = 0.046 and 0.010). Also, only TILs was a significant risk factor for recurrence and survival among the PD-1, PD-L1, PD-L2, CTLA-4, and TILs (HR = 0.217 CI: 0.070-0.679, p = 0.009 and HR = 0.566, CI: 0,321-980, p = 0.048). Similarly, for the TILs score: > 1 was significant for DFS. (Long-Rank = 0.009). The examined markers and TILs scores were not a significant predictive factor for OS. CONCLUSION: An increase in TILs density in LSCCs is associated with a better prognosis. However, PD-1, PD-L1, PD-L2, CTLA-4 could not be associated with prognosis. Controlled studies combined with immunotherapy treatment results are needed to reveal their role as a marker and prognostic factor of the anti-tumor immune response.

Oleuropein Effect on Noise-Induced Hearing Loss.

BACKGROUND: To investigate the possible protective activity of oleuropein compound on noise-induced hearing loss in rats. METHODS: Twenty-eight adult male albino rats were divided into 4 groups. Control normal saline (n=7) group was kept noise-free. Control oleuropein group (n=7) group was kept noise-free and was administered with 50 mg/kg/day oleuropein. The experimental normal saline (n=7) group was subjected to noise. The experimental oleuropein (n=7) group was subjected to noise and was administered with 50 mg/kg/day oleuropein. The experimental groups were subjected to 4 kHz octave noise with a frequency of 120 dB Sound Pressure Level (SPL) for 4 hours. Hearing level measurements were performed with auditory brainstem response and distortion-product otoacoustic emission tests before and after the 1st, 7th, and 10th day of the noise exposure. On the 10th day, rats were sacrificed. The temporal bones of the rats were removed and the cochlea and spiral ganglion cells were evaluated using hematoxylin-eosin staining under light microscopy. RESULTS: Better hearing thresholds were achieved in the experimental oleuropein group compared to the experimental normal saline group at 8 kHz, 12 kHz, 16 kHz, and 32 kHz frequencies (P < .05). Although no statistically significant difference was found between the groups, in the experimental normal saline group, the percentage of damaged spiral ganglion cells was higher than the experimental oleuropein group. CONCLUSION: Our findings suggest that oleuropein may have a partial protective effect against noise-related hearing loss. However, further research with higher doses is needed to justify this protective effect.