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Objective@#To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy.@*Methods@#This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS.@*Results@#There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109).@*Conclusion@#There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.
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Objective To investigate the relationship between the plasma level of interleukin 15 (IL-15) and the quantitative myasthenia gravis (QMG) score in late-onset myasthenia gravis (MG).Methods The blood samples of 86 patients (over 50 years old) who admitted to Henan Provincial People's Hospital between 2010 and 2016 were collected at two different stages:pre-treatment and six months post-treatment.The diagnosis was verified by characterizing clinical manifestation,neostigmine testing,electromyographic recording,thymic imaging and plasma anti-acetylcholine receptor (AchR).All the patients were divided further by modified Osserman classification and treated with cholinesterase inhibitor and glucocorticoid.The blood samples of 42 healthy controls were also collected from their physical examination at the end of 2016.Enzyme linked immunosorbent assay was used to evaluate the levels of IL-15 in plasma.Thymectomy was performed on patients with MG accompanied by thymoma.The possible correlation between the expression of IL-15 and the QMG scores,different types were analyzed.Results Before treatment,the levels of IL-15 in the plasma were much higher in the late onset MG patients (both ocular and generalized) than in the healthy controls ((5.75± 1.57) pg/ml vs (4.40±0.50) pg/ml,t=2.925,P＜0.01).And the late onset MG patients with thymoma showed higher level of IL-15 compared to the healthy controls ((7.39±0.84) pg/ml vs (4.40±0.50) pg/ml,t=3.925,P＜0.01).Further analysis showed that the IL-15 levels in all the MG patients with different pathological types of thymoma were higher than in the healthy controls.In the mild type of late-onset MG patients without thymoma,the IL-15 level was not increased ((4.49±0.74)pg/ml vs (4.40±0.50) pg/ml,t=1.752,P＞0.05) and in the severe type of late-onset MG patients without thymoma,the IL-15 level was mildly increased ((4.76±0.75) pg/ml vs (4.40±0.50) pg/ml,t=2.462,P＜0.05) compared to the healthy controls.Furthermore,the IL-15 level decreased dramatically upon the therapy in all the MG patients,especially in the late-onset MG patients with thymoma.Moreover,IL-15 was positively correlated with QMG scores before treatment (r=0.375,P＜0.01),especially in the late-onset MG patients with thymoma (r=0.823,P＜0.01),but not in the late-onset MG patients without thymoma (r=0.039,P＞0.05).IL-15 and QMG scores returned to normal six months after treatment.Conclusions IL-15 is increased in the plasma of late-onset MG patients,and is positively correlated with the QMG scores,especially in the late-onset MG patients with thymoma.In addition,IL-15 is decreased upon the therapy in the MG patients.
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Objective@#To investigate the level of interleukin-6 (IL-6) and the effect of valproic acid(VPA) administration on IL-6 promoter methylation, further to explore the epigenetic mechanism in febrile seizures.@*Methods@#Sprague-Dawley (SD) rats (21 day) were randomly divided into control group (n=12) and febrile seizure (FS) group (n=12), and seizures were generated using hot bath methods and evaluated by racine score and electroencephalogram (EEG). The IL-6 protein and mRNA levels were detected using ELISA and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively.Rat C6 cell line was cultured and randomly divided into control, VPA(0.2 mol/L), hyperthermia(43.5 ℃, 1 h), hyperthermia (43.5 ℃, 1 h)+VPA (0.2 mol/L) groups.The methylation status of IL-6 promoter in FS rats and the effect of VPA on IL-6 methylation in C6 cell line were examined by bisulfite sequencing polymerase chain reaction (BSP) to determine the epigenetic regulation of IL-6 level in FS.@*Results@#Racine score and EEG results showed that the frequency and amplitude of neuronal discharge increased after hot water bath in rats, and the latency of convulsion was shorter.The expression levels of IL-6 mRNA and protein were significantly increased in Fs group compared with those in control group(mRNA: Control: 0.98±0.34; FS: 2.85±0.39, P<0.05; Protein: Control: (2 824.33±169.20)pg/ml; FS: (3 514.58±86.4)pg/ml, P<0.01). The methylation of IL-6 promoter in FS group (84% (21/25)) was lower than that in control group (100% (25/25)) (P<0.05). A significant increase in methylation of IL-6 promoter was observed in C6 cell line from VPA combined with hyperthermia (96% (24/25)) but no change was showed in that from VPA alone (100% (25/25)) compared with that from control(100% (25/25)).@*Conclusion@#IL-6 level is up-regulated in FS rats, and the hypomethylation or demethylation of the IL-6 promoter region might increase the IL-6 level.VPA administration can elevate its methylation level, which provides a strong experimental basis for the future study of the epigenetic mechanism in FS.
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Objective:To investigate the expression and clinical significance of PD-L1 in colorectal cancer (CRC). Methods:A total of 210 CRC patients who accepted radical surgery in our hospital from January 2015 to January 2016 were divided into three groups, namely, high-frequency microsatellite instability (MSI-H), low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS). The expression of PD-L1 was detected by immunohistochemistry, and the expression characteristics of PD-L1 in different types of CRC were analyzed. Results:CRC cases with low differentiation had a higher expression of PD-L1 than CRC patients with high differ-entiation (P<0.05). PD-L1 had a positive rate of 75.8%in the MSI-H group and a rate of 9.3%in the MSI-L and MSS groups, wherein the difference between the two groups was statistically significant (P<0.05). Conclusion:PD-L1 was positively expressed in some CRC tu-mor tissues, and its positive rate was significantly higher in MSI-H than in MSI-L and MSS. The therapeutic effect of a PD-L1 blocker for patients with MSI-H CRC might be preferable.
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Objective To study PTEN protein expression and clinical significance in patients with diffuse large B cell lymphoma. Methods Immunohistochemical staining was used to determine the PTEN protein expression in 40 cases of primary diffuse large B lymphoma tissuse. The results were analyzed by Kaplan-Merie survival analysis, Log-Rank test and Logistic regression analysis. Results PTEN protein was positive in 16 cases and negative in 24 cases. There was no significant difference between two groups in twoyear overall survival rate(62.5 % vs 66.7 %, P >0.05). Survival analysis showed that patient' s survival time gradually were reduced with extended time between PTEN protein-positive group and negative group, lower in PTEN-positive group than the negative group, but there was no significant difference in survival curve (P >0.05) in the two groups. We compared characteristics of patients between PTEN protein positive and negative groups,including molecular type, patient' s age, stage, LDH, physical score and extranodular invasion, there was no significant difference among them. PTEN protein was not correlated with prognosis, while International Prognosis Index(IPI) was still a risk factor (OR >1). Conclusion PTEN protein expression may not predict the outcome in diffuse large B cell lymphoma, but IPI still is a predictor.
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Objective To discuss the clinical and pathological characteristics, treatment results and prognosis of primary parotid malignant lymphoma. Methods Pathological subtypes, clinical stages and treatment of the 24 patients with primary parotid malignant lymphoma were retrospectively analysed. Kaplan-Meier method was used in the survival analysis and Log-Rank method was used in the statistic study. Results The 5-year progression free survival (PFS) and overall survival (OS) were 79.2 % and 83.3 %, respectively. The 5-year PFS and OS were 89.5 % and 94.7 % for 19 patients with low-grade malignant lymphoma (including MALTL and Ⅰ/Ⅱ grade FL). The differences of the 5-year PFS and OS of 9 patients received chemotherapy and of 10 patients with on chemotherapy had no statistical significance. Conclusion The incidence of primary parotid malignant lymphoma is low, at earlier clinical stage, and most of its pathological subtype were B-cell low-grade malignant non-Hodgkin lymphoma. Surgery and/or radiotherapy should be the first choice for patients with early stage low-grade malignant lymphoma, whereas combined modality therapy was probably the best choice for patients with DLBCL.
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Objective To investigate the pathologic characteristics of skip metastases of mediastinal lymph node in lung cancer. Methods Of 398 lung cancer patients who underwent radical resection and extensive lymph node dissection. 47 patients were diagnosed as with skip N 2 metastases, and their mediastinal lymph nodes were analyzed. Results The skip N 2 metastases of lung cancer appeared as single group or multi-group. The commonest metastatic site was the 7th group lymph node (28.4%), then the 4th, 3rd and 5th group, rating 24.2%, 15.8% and 10.5%, respectively. For cases with squamous cell carcinoma or adenocarcinoma, no any skip N 2 metastasis occurred for the tumor less than 1 cm in diameter, for tumor greater than 1 cm in diameter, the skip N 2 metastasis increased with tumor size. The incidence skip N 2 metastasis of low-grade differentiated adenocarcinoma was significantly higher than high-grade differentiated adenocarcinoma (P
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<p><b>BACKGROUND</b>To investigate pathologically the characteristics of proximal bronchial invasion of lung cancer, and to provide the theoretic basis for the selection of a proper operation mode.</p><p><b>METHODS</b>A total of 398 patients with lung carcinoma underwent radical pulmonectomy and systematic lymphadenectomy. The proximal bronchi and the hilar and mediastinal lymph nodes of their operatively resected specimens were selected for pathological study.</p><p><b>RESULTS</b>(1)The direct invasion of cancerous cells through mucous, submucous or multiple layers was the most frequent way during lung cancer spread, rating 9.3%, 21.8% and 68.9% respectively. 96.4% of the cancerous invasion occurred at the proximal bronchial wall less than 1.5 cm apart from the cancer margin. The extension of invasion correlated with the histopathologic type of cancer, mode of invasion and TNM classification. (2)The cancer infiltration by the nodes metastasizing into the bronchus wall (bronchial external tunica or cartilage) was also an important way for the cancer to spread, especially in adenocarcinoma. The poor differentiated adenocarcinoma has significantly higher metastatic rate and infiltration rate than the well differentiated ( P < 0.01, P < 0.01). There were 22 such cases, including 3 of lobar bronchus wall invaded by N1 metastasis and 19 of main bronchus wall by N2 metastasis.</p><p><b>CONCLUSIONS</b>For radical removal of tumor, the key point for selecting a rational operation mode is to keep a distance of 1.5 cm or more between the excision margin of the bronchus and the tumor, to pay attention to the bronchial wall invasion caused by the metastatic lymph nodes, even in peripheral adenocarcinoma, and to dissect extensively and completely the lymph nodes of the hilar and upper and lower mediastinum at the homolateral thoracic cavity.</p>