1.Immunohistochemical Detections of EGFR Mutations in NSCLC
LIU CHANG ; XU DONGBO ; ZHONG DIANSHENG
Chinese Journal of Lung Cancer 2014;(9):701-705
In recent years, it has been well known that non-small cell lung cancer (NSCLC) patients with muta-tions of epidermal growth factor receptor (EGFR) response better to EGFR-tyrosine kinase inhibitor treatment. Although DNA-based assays (e.g. DNA sequencing) are the most frequently used and a relatively reliable method to detect EGFR muta-tions, they are complex, time-consuming and relatively expensive for routine use in clinical laboratories, besides they require high quality tumor samples. In contrast, the immunohistochemistry (IHC) methods make up fully for the above shortcomings and can serve as screening tests for EGFR mutations. However, there are many factors that can inlfuence the results of IHC methods, such as different staining procedures, different antigen retrieval solutions and different sets of criteria, etc. hTus the IHC methods for detecting EGFR mutations have not been widely used in clinic and only in the research stage. hTis article re-views the use of IHC methods by different researchers and further discusses how to make the IHC methods work best for the detection of EGFR mutations.
2.Frst-line treatment of Zorifertinib in EGFR-mutant NSCLC with CNS metastases:a report of two cases
Dan XU ; Xia LIU ; Diansheng ZHONG
Tianjin Medical Journal 2024;52(3):315-318
Objective To investigate the efficacy of Zorifertinib in first-line treatment of patients with untreated epidermal growth factor receptor(EGFR)mutation in non-small-cell lung cancer(NSCLC)with central nervous system(CNS)metastases.Methods Two patients received Zorifertinib as first-line treatment.The response of tumor treatment was evaluated by response evaluation criteria in solid tumors version 1.1(RECEST v1.1)and RANO criteria for brain metastases(RANO-BM).Results Case 1 had EGFR exon 19del mutation and multiple brain metastases at baseline.After 51.4 months of treatment with Zorifertinib,case 1 still maintained partial response(PR)in lung lesions and complete response(CR)in intracranial lesions.Case 2 had EGFR exon 19del mutation and a single brain metastasis at baseline.Case 2 achieved PR in lung lesions and CR in intracranial lesions during the treatment with Zorifertinib.After 13.7 months,lung disease progression(PD)and new single brain metastases occurred.The comprehensive evaluation was PD.Case 1 had three-grade treatment-related adverse events(TRAEs),including dry skin,and other TRAEs were rash,abnormal liver function and diarrhea.The TRAEs were generally controllable.Conclusion Zorifertinib has a good effect on controlling intracranial and extracranial lesions in patients with EGFR-mutated NSCLC with CNS metastases.The efficacy of Zorifertinib is consistent with the EVEREST study.Zorifertinib can be one of the first-line initial treatment options.
3.Immunohistochemical detections ofEGFRstatus in NSCLC
WANG JIE ; LIU CHANG ; ZHONG DIANSHENG ; XU DONGBO ; NING CHAO ; MA QING
Chinese Journal of Lung Cancer 2015;18(4):212-218
Background and objective Patients with non-small cell lung cancer (NSCLC) harboring mutations of the epidermal growth factor receptor (EGFR) respond well to EGFR-tyrosine kinase inhibitor therapy. Immunohistochemistry (IHC) is a simple and widely used technique in clinical pathology laboratories. IHC also features cost effectiveness and rapid detection ofEGFR mutations compared with molecular methods. hTis study aims to determine the accuracy of IHC forEGFR mutation detection in NSCLC.Methods Specimens (obtained from surgery or biopsy) from 97 NSCLC cases were stained through IHC with mutation-specific antibodies. The clinicopathological features of patients with positive immunostaining results were analyzed. Positive specimens were subjected to liquid chip technology to detect the actual EGFR status. Forty NSCLC specimens obtained from surgery and conifrmed to haveEGFR mutations through liquid chip technology were collect-ed. These specimens were then subjected to IHC analyses with mutation-speciifc antibodies. The sensitivity of IHC in detect-ingEGFR mutations was calculated.Results Seventeen of the 97 NSCLC specimens were stained positive, and positive results were mostly observed in females, patients with adenocarcinoma, and non-smokers. About 76.9% of specimens with positive IHC results harbored mutations. The sensitivity of IHC was 40% among the 40 cases identiifed as containingEGFR mutations through liquid chip technology.Conclusion The strong positive immunostaining result is accurate, but the sensitivity of the method may not be optimal and signiifcantly varies in different studies. The widespread application of IHC in clinics must be further investigated.
4.Inlfuence of Immunohistochemistry Scoring Criteria in Detecting EGFR Mutations
FENG XIN ; LIU CHANG ; ZHONG DIANSHENG ; XU DONGBO ; NING CHAO ; WANG JIE
Chinese Journal of Lung Cancer 2015;(12):740-744
Background and objectiveAppropriate immunohistochemistry (IHC) scoring criteria can guarantee the reliability of mutation detection results. Most current studies suggest that the “four-grade criterion” may be the best among all scoring systems. hTe aim of this study is to discuss the inlfuence of different four-grade immunohistochemistry scoring criteria on the test results.MethodshTree different four-grade immunohistochemistry scoring criteria were respectively used to evaluate the EGFR status of 83 cases of non-small cell of lung cancer (NSCLC) samples. hTe sensitivity, speciifcity, positive predictive value (PPV), negative predictive value (NPV), the agreement of each criterion compared with the gold standard, and whether statistical signiifcance exists between each criterion were calculated.Results No statistical difference was found among the three criteria in detectingEGFR mutations. All three criteria exhibit considerably better speciifcity than sensitivity. For samples with scores of “3+”, PPV could reach up to 100%.ConclusionNo deifnite best criterion is among different four-grade scoring criteria. Regardless of the kind of criterion used, the speciifcity of IHC method in detectingEGFR mutations is markedly better than the sensitivity. For samples with scores of “3+”, mutation status can be conifrmed, and samples can receive EGFR-TKI therapy directly.
5.Bioassay-guided isolation of functional components from hot water extract of Chlorella pyrenoidosa.
Jing JIA ; Diansheng XU ; Xiuyuan ZHUANG ; Daojing ZHANG ; Liming TAO ; Yuanguang LI
Chinese Journal of Biotechnology 2017;33(5):743-756
The main functional ingredients of hot water extract of Chlorella pyrenoidosa (CPE) were investigated through a bioassay-guided fractionation based on free radical scavenging and macrophage proliferation effects. The main functional ingredients of CPE were polysaccharides (PS) that were isolated by high pressure extraction, Sevag method, ethanol precipitation and ultrafiltration separation. Crude polysaccharides were further separated and purified by ion exchange chromatography DEAE52 and size exclusion chromatography Sephadex G-100. The purified fractions were analyzed by gel permeation chromatography. Molecular weights of the purified fractions PS-1-4-2, PS-1-3-2 and PS-2-3-3 were 3.97×10⁴, 2.28×10⁴ and 4.1×10³ Da, respectively. Bioassay-guided fractionation results indicated that CPE could remove free radicals and promote Ana-1 cells proliferation, mainly due to its various components working together. The components of free radicals scavenging mainly concentrated in PS-1-3, PS-1-4, PS-2-3 and PS-2-4. The components of Ana-1 proliferation mainly concentrated in PS-1-3, PS-1-4 and PS-2-3. This study established the activity screening method of main functional component from CPE, and got three new functional ingredients. It can be used to guide the development of high value products, further promote the industrialization process of microalgae energy, and realize microalgae 'high value products, microalgae energy and microalgae carbon' integration of exemplary role.