Imaging Characteristics Predictive of Cervical Extranodal Tumor Extension in Patients With Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: The aims of the study were to determine the predictive imaging findings of extranodal extension (ENE) in metastatic cervical lymph nodes of head and neck squamous cell carcinoma and to investigate the interobserver agreement among radiologists with different experience levels. MATERIALS AND METHODS: Patients with cervical lymph node dissection and who had metastatic lymph nodes and preoperative imaging were included. Three radiologists evaluated nodal necrosis, irregular contour, gross invasion, and perinodal fat stranding. They also noted their overall impression regarding the presence of the ENE. Sensitivity, specificity, odds ratios based on logistic regression, and interobserver agreement of ENE status were calculated. RESULTS: Of 106 lymph nodes (that met inclusion criteria), 31 had radiologically determined ENE. On pathologic examination, 22 of 31 nodes were positive for ENE. The increasing number of metastatic lymph nodes was associated with the presence of the ENE ( P = 0.010). Irregular contour had the highest sensitivity (78.6%) and gross invasion had the highest specificity (96%) for the determination of the ENE. The radiologists' impression regarding the presence of the pathlogical ENE had 39.3% sensitivity and 82% specificity. Metastatic lymph nodes with a perinodal fat stranding and with the longest diameter of greater than 2 cm were found to be strong predictors of the ENE. The gross invasion demonstrated the highest κ value (0.731) among the evaluated imaging criteria. CONCLUSIONS: In the assessment of ENE, the gross invasion had the highest specificity among imaging features and showed the highest interobserver agreement. Perinodal fat stranding and the longest diameter of greater than 2 cm in a metastatic lymph node were the best predictors of the ENE.

Relationship of E-cadherin, Beta-catenin, N-cadherin, ZEB1 and αSMA as Epithelial Mesenchymal Transition markers with prognostic factors in early and advanced stage laryngeal squamous cell carcinomas.

Aims: To investigate the relationship between E-cadherin, beta-catenin, N-cadherin, ZEB1, and αSMA as epithelial-mesenchymal transformation markers with tumor stage, lymph node metastasis (LNM), and overall survival (OS) in laryngeal squamous cell carcinomas (LSCC). Materials and Methods: A total of 100 cases diagnosed with LSCC were included in the study. Data about the lymphovascular invasion (LVI), perineural invasion (PNI), necrosis, and LNM were recorded by evaluating hematoxylin-eosin-stained slides. Markers of E-cadherin, beta-catenin, N-cadherin, ZEB1, and αSMA were applied to the sections prepared from paraffin blocks of tumor samples. Results: Ninety-five male and five female patients were included in the study, and 38 of them exited. A significant relationship was observed between OS with advanced tumor stage, presence of LNM and PNI. A significant relationship was found between increased tumor Zeb1 expression and advanced tumor stage. In univariate and multivariate analyses, a significant negative relationship with OS, and increased Zeb1 expression in tumor and tumor stroma was seen. Any relationship was not observed between E-cadherin, beta-catenin, N-cadherin, and αSMA and OS. Conclusion: Among the EMT markers, we evaluated in our study, it was seen that Zeb1, which is an EMT transcription factor, is associated with tumor stage, LNM, and OS. Remarkably, Zeb1 expression observed in tumor stroma was also significant for OS. Any similar data reported for LSCCs have not been encountered in the literature, and it was thought that it would be appropriate to support our findings with further studies to be performed on this subject.

Vitamin C (Ascorbic acid) protects from neuropathy caused by cisplatin, through enhanced heat shock protein-70 and reduced oxidant effect.

OBJECTIVE: We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats. METHODS: In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed. RESULTS: Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05). CONCLUSIONS: We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.

Vitamin C (Ascorbic acid) protects from neuropathy caused by cisplatin, through enhanced heat shock protein-70 and reduced oxidant effect

SUMMARY OBJECTIVE: We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats. METHODS: In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed. RESULTS: Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05). CONCLUSIONS: We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.

Differentiation of brain metastases originating from lung and breast cancers using apparent diffusion coefficient histogram analysis and the relation of histogram parameters with Ki-67.

PURPOSE: A fast, reliable and non-invasive method is required in differentiating brain metastases (BMs) originating from lung cancer (LC) and breast cancer (BC). The aims of this study were to assess the role of histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating BMs originated from LC and BC, and then to investigate further the association of ADC histogram parameters with Ki-67 index in BMs. METHODS: A total of 55 patients (LC, N = 40; BC, N = 15) with BMs histopathologically confirmed were enrolled in the study. The LC group was divided into small-cell lung cancer (SCLC; N = 15) and non-small-cell lung cancer (NSCLC; N = 25) groups. ADC histogram parameters (ADCmax, ADCmean, ADCmin, ADCmedian, ADC10, ADC25, ADC75 and ADC90, skewness, kurtosis and entropy) were derived from ADC maps. Mann-Whitney U-test, independent samples t-test, receiver operating characteristic (ROC) analysis and Spearman correlation analysis were used for statistical assessment. RESULTS: ADC histogram parameters did not show significant differences between LC and BC groups (p > 0.05). Subgroup analysis showed that various ADC histogram parameters were found to be statistically lower in the SCLC group compared to the NSCLC and BC groups (p < 0.05). ROC analysis showed that ADCmean and ADC10 for differentiating SCLC BMs from NSCLC, and ADC25 for differentiating SCLC BMs from BC achieved optimal diagnostic performances. Various histogram parameters were found to be significantly correlated with Ki-67 (p < 0.05). CONCLUSION: Histogram analysis of ADC maps may reflect tumoural proliferation potential in BMs and can be useful in differentiating SCLC BMs from NSCLC and BC BMs.

Granulomatous Mastitis: A Clinical and Diagnostic Dilemma.

OBJECTIVE: Granulomatous mastitis (GM) is a challenging inflammatory disorder of the breast. In this study we aimed to present the detailed clinical and morphological features of GM cases, diagnostic clues for specific and idiopathic etiologies, the difficulties in evaluating trucut biopsies, and the results of different therapeutic approaches. MATERIAL AND METHOD: We retrospectively analysed the clinical, radiological and morphological features of 114 GM cases diagnosed with fine needle aspiration, and trucut, incisional, and excisional biopsy. RESULTS: The mean age was 35.8. Only eight cases were older than 45 years. Bilateral involvement was observed in 4 (3.5%) cases. The most common clinical symptoms were breast mass/abscesses, tenderness, and skin changes. Microbiological culture was positive in 4 cases for gram-positive bacteria. Only 3 cases showed a positive tuberculin/PCR test for tuberculosis. The major USG finding was a hypoechoic well-defined or ill-defined mass/abscess; MRI finding was heterogeneous non-mass contrast enhancement. Cases diagnosed with cytology (35 cases) did not have breast malignancy either in their history or clinical follow up period. Fine needle aspiration cytology materials revealed epitheloid granulomas mixed with neutrophils, lymphocytes accompanied by giant cells, and suppurative necrosis. Histopathological reevaluation of 65 trucut/incisional/ excisional biopsies revealed granuloma formation in 65 (100%), Langhans type giant cells in 59 (90.7%), microabscess formation in 41 (63%), caseous necrosis in 1 (1.5%), neutrophilic cysts in 30 (46.1%), eosinophilic infiltration in 48 (73.8%), interlobular inflammation in 14 (21.5%), fat necrosis in 5 (7.6%), ductal ectasia in 6 (9.2%), and lactational changes in 4 (6.1%) cases. Granulomas were lobulocentric in 58 cases, foreign body type/fat necrosis-related in 6 case, and periductular in 1 case. Cystic neutrophilic granulomatous mastitis was observed in one case. We also evaluated the histochemical stains of these 65 biopsies. Only one sample was positive for acido-resistant bacilli (ARB) by the EZN method and one sample was positive for gram-positive bacilli by gram stain. CONCLUSION: Small, superficial trucut biopsies may cause difficulties in determining the etiology and differential diagnosis of granulomatous mastitis. For optimal management and timing the appropriate therapy, the ideal biopsy procedure, special stains, and a multidisciplinary team consisting of the surgeon, pathologist, and radiologist are the most important issues.

The Significance of Histopathologic Assessment in Bone Marrow Disease in Neuroblastoma.

OBJECTIVE: Neuroblastoma (NB) is the most common extracranial solid tumor in children and is responsible for 12% of cancer-related deaths. The status of metastatic disease in the bone marrow (BM) is a predictor of poor outcome. The purpose of this study was to investigate the predictive significance of histopathological examination of BM in NB. MATERIAL AND METHOD: The study included 61 cases with archival bone marrow biopsy tissues. The cases were evaluated regarding the percentage of metastatic tissue and its differentiation. Primary tumor slides were also reviewed to perform the Shimada classification based on the differentiation status and mitosis-karyorrhexis index. The patients' age, gender, NMYC amplification, clinical risk group, and disease outcome were also noted. RESULTS: Of the 61 cases, 17 had BM involvement. Of those, eight cases (47.1%) were refractory NB showing disease relapse. Based on BM examination, five cases (29.4%) were categorized as complete response, seven (41.2%) as progressive disease, three (17.6%) as minimal disease, and two (11.8%) as stable disease. The progressive disease category was significantly related with refractory disease and NMYC amplification along with the high-risk category (p =0.002 and p= 0.003 respectively). Undifferentiated histology and presence of more than 20% of tumor tissue in the BM biopsy at diagnosis were significantly associated with the progressive disease category (p=0.01 and p < 0.001, respectively). CONCLUSION: We conclude that evaluating the percentage of metastatic tumor tissue and tumor differentiation in BM biopsies is of clinical importance in the management of neuroblastoma patients.

The association between the histopathological features and microsatellite instability in young patients with urothelial carcinoma of the bladder.

OBJECTIVE: Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. METHODS: A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. RESULTS: Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. CONCLUSIONS: Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.

A Nobel-Winning Scientist: Aziz Sancar and the Impact of his Work on the Molecular Pathology of Neoplastic Diseases.

Aziz Sancar, Nobel Prize winning Turkish scientist, made several discoveries which had a major impact on molecular sciences, particularly disciplines that focus on carcinogenesis and cancer treatment, including molecular pathology. Cloning the photolyase gene, which was the initial step of his work on DNA repair mechanisms, discovery of the "Maxicell" method, explanation of the mechanism of nucleotide excision repair and transcription-coupled repair, discovery of "molecular matchmakers", and mapping human excision repair genes at single nucleotide resolution constitute his major research topics. Moreover, Sancar discovered the cryptochromes, the clock genes in humans, in 1998, and this discovery led to substantial progress in the understanding of the circadian clock and the introduction of the concept of "chrono-chemoterapy" for more effective therapy in cancer patients. This review focuses on Aziz Sancar's scientific studies and their reflections on molecular pathology of neoplastic diseases. While providing a new perspective for researchers working in the field of pathology and molecular pathology, this review is also an evidence of how basic sciences and clinical sciences complete each other.

The association between the histopathological features and microsatellite instability in young patients with urothelial carcinoma of the bladder

SUMMARY OBJECTIVE: Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. METHODS: A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. RESULTS: Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. CONCLUSIONS: Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.

Association of apparent diffusion coefficient with Ki-67 proliferation index, progesterone-receptor status and various histopathological parameters, and its utility in predicting the high grade in meningiomas.

BACKGROUND: Accurate preoperative determination of the histological grade and cellular proliferative potential of meningioma by non-invasive imaging is of paramount importance. PURPOSE: To evaluate the utility of apparent diffusion coefficient (ADC) in determining the histological grade of meningioma, and to investigate the correlation of ADC with Ki-67 proliferation index (PI), progesterone receptor (PR) status, and a number of other histopathological parameters. MATERIAL AND METHODS: Histopathologically confirmed 94 meningioma patients (72 low-grade, 22 high-grade) who had undergone preoperative diffusion-weighted imaging were retrospectively evaluated. ADC values were obtained by manually drawing the regions of interest (ROIs) within the solid components of the tumor. The relationship between ADC and Ki-67 values, PR status, and multiple histopathological parameters were investigated, and the ADC values of high-grade and low-grade meningiomas were compared. Independent sample t-test, Mann-Whitney U test, receiver operating characteristic, Pearson correlation, and multiple logistic regression analysis were used for statistical assessment. RESULTS: All ADC and rADC values were significantly lower in high-grade meningiomas than in low-grade meningiomas (all P < 0.05). ADC values showed significantly negative correlations with Ki-67 and mitotic index (P < 0.001 for each). Numerous ADC parameters were significantly lower in meningiomas demonstrating hypercellularity and necrosis features (P < 0.05). ADC values did not show a significant correlation with PR score (all P > 0.05). CONCLUSION: ADC can be utilized as a reliable imaging biomarker for predicting the proliferative potential and histological grade in meningiomas.

Diagnostic role of apparent diffusion coefficient combined with intratumoral susceptibility signals in differentiating high-grade gliomas from brain metastases.

OBJECTIVE: The aim of this study was to assess whether tumoral and peritumoral apparent diffusion coefficient values and intratumoral susceptibility signals on susceptibility-weighted imaging could distinguish between high-grade gliomas and brain metastases, and to investigate their associations with the Ki-67 proliferation index. MATERIALS AND METHODS: Fifty-seven patients with pathologically confirmed diagnoses of either high-grade glioma or brain metastasis were enrolled in this study (23 with high-grade gliomas and 34 with brain metastases). The minimum and mean apparent diffusion coefficients in the enhancing tumoral region (ADCmin and ADCmean) and the minimum apparent diffusion coefficient in the peritumoral region (ADCedema) were measured from apparent diffusion coefficient maps, and intratumoral susceptibility signal grades acquired by susceptibility-weighted imaging were calculated. Ki-67 proliferation index values were obtained from the hospital database. These parameters were evaluated using the Mann-Whitney U test, independent-sample t-test, Spearman correlation analysis, receiver operating characteristic curve, and logistic regression analyses. RESULTS: ADCmean, ADCmin values, and intratumoral susceptibility signal grades in brain metastases were significantly lower than those in high-grade gliomas (all p < 0.05). Ki-67 proliferation index values showed significant correlations with ADCmean, ADCmin, and intratumoral susceptibility signal grade in brain metastases (all p < 0.05), but no correlation was found in high-grade gliomas (all p > 0.05). According to receiver operating characteristic curve analysis, ADCmean achieved the highest diagnostic performance for discriminating high-grade gliomas from brain metastases. Furthermore, the combination of tumoral apparent diffusion coefficient parameters with intratumoral susceptibility signal grade provided a higher area under the curve than univariate parameters. CONCLUSION: The combination of tumoral apparent diffusion coefficient with intratumoral susceptibility signal grade can offer better diagnostic performances for differential diagnosis. Apparent diffusion coefficient and intratumoral susceptibility signal may reflect cellular proliferative activity in brain metastases, but not in high-grade gliomas.

Primary non-Hodgkin's lymphoma masquerading as cervical cancer.

Genital tract lymphomas are rare entities that can be diagnosed at advanced stages. The uterine cervix is not generally infiltrated by lymphoma. Nevertheless it can be seen as a consequence of either a systemic disease or primary disease. The infrequency of primary cervical lymphoma makes the diagnosis challenging.

How to Set Up a Molecular Pathology Lab: A Guide for Pathologists.

In today's pathology practice, pathologists combine molecular tests with conventional histopathological methods. Pathology laboratories should therefore be designed and operated in accordance with the requirements of molecular testing procedures. While the specifics of the requirements may vary depending on the spectrum of the tests that will be performed, there are several basic criteria that need to be fulfilled for standardization. Adequate space, appropriate equipment and qualified personnel are required to establish a molecular pathology laboratory. One of the most important points that should be taken into consideration while designing a molecular pathology laboratory is to create a plan to prevent contamination. As molecular diagnosis has a major role in treatment decisions, the management of the molecular pathology laboratory is of utmost importance. In this review, the criteria required to establish an optimal molecular pathology laboratory will be reviewed.

Relationship between local and systemic inflammatory response and prognosis in laryngeal squamous cell carcinoma.

OBJECTIVE: Laryngeal squamous cell carcinoma (LSCC) is the most frequently seen head and neck malignancy. Despite improvements in the treatment modalities within the last 20 years, the desired improvement in survival outcomes has not been achieved yet which led researchers to investigate factors that might affect prognosis in LSCCs. METHODS: A total of 116 previously operated patients were included in this study. To assess systemic inflammation, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The cut-off values for NLR and PLR were accepted as 2.79 and 112, respectively. To evaluate intratumoral inflammation, hematoxylin-eosin stained tumor sections were evaluated. Tumor-infiltrating lymphocyte (TIL) densities in the tumor area were scored as 1+, 2+ and 3+. RESULTS: The mean overall survival was 29.5±17.7 months. In univariate analysis, a statistically significant correlation was seen between age group of 60 years, tumor stage, site and OS (p=0.025, p=0.026, p=0.029). There was no statistically significant relationship between PLR, NLR and TIL density and OS. In the multivariate analysis, the 60-year-old group and tumour stage were still significantly associated with the OS (p=0.033, p=0.046). CONCLUSION: Age and tumor stage were significantly associated with survival in our study, but contrary to the literature, no correlation was found between local and systemic inflammatory response.

A grading dilemma; Gleason scoring system: Are we sufficiently compatible? A multi center study.

OBJECTIVE: Gleason scoring is the grading system which strongly predicts the prognosis of prostate cancer. However, even being one of the most commonly used systems, the presence of different interobserver agreement rates push the uropathologists update the definitons of the Gleason patterns. In this study, we aimed to determine the interobserver agreement variability among 7 general pathologists, and one expert uropathologist from 6 different centers. METHODS: A set of 50 Hematoxylin & Eosin stained slides from 41 patients diagnosed as prostate cancer were revised by 8 different pathologists. The pathologists were also grouped according to having their residency at the same institute or working at the same center. All pathologists' and the subgroups' Gleason scores were then compared for interobserver variability by Fleiss' and Cohen's kappa tests using R v3.2.4. RESULTS: There were about 8 pathologists from 6 different centers revised all the slides. One of them was an expert uropathologist with experience of 18 years. Among 7 general pathologists 4 had surgical pathology experience for over 5 years whilst 3 had under 5 years. The Fleiss' kappa was found as 0.54 for primary Gleason pattern, and 0.44 for total Gleason score (moderate agreement). The Fleiss' kappa was 0.45 for grade grouping system. CONCLUSION: Assigning a Gleason score for a patient can be problematic because of different interobserver agreement rates among pathologists even though the patterns were accepted as well-defined.

Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors.

PURPOSE: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. METHODS: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-L1 and mRNA was evaluated with IHC. RESULTS: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). CONCLUSION: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas.

Protective Effect of All-Trans Retinoic Acid in Cisplatin-Induced Testicular Damage in Rats.

PURPOSE: To investigate the effects of all-trans retinoic acid (ATRA) in cisplatin (CP)-induced testicular damage in rats. MATERIALS AND METHODS: Twenty-eight male Wistar rats were divided into four groups: Control, ATRA alone, ATRA+CP, and CP alone. Body weight, testicular weight, sperm count, sperm motility, percentage of abnormal sperm, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in testicular tissue, and testicular histopathology were compared among groups. RESULTS: The sperm count and motility significantly decreased and the percentage of abnormal sperm significantly increased in the CP group compared to the control and ATRA groups. CP+ATRA administration significantly increased the sperm count and motility, but reduced the abnormal sperm count. CP administration significantly increased TOS and OSI compared to the control group and the other groups. Administering CP+ATRA significantly decreased TOS and the OSI in testicular tissue and reduced spermatogenesis, but increased the Johnsen score. CONCLUSIONS: The destructive effects of CP treatment on testicular tissue and spermatogenesis were reduced by administering ATRA.