Tell your genetic story: the same histopathology, why the survival period is very different?
Release date: 2016-06-15 The 2016 World Health Organization (WHO) Classification of Central Nervous System Tumors was first classified for molecular classification based on histological classification of CNS tumors. Thus, a new concept of CNS tumor diagnosis in the molecular age has been established. Glioma is the most common primary central nervous system tumor. Molecular typing is of great significance for its diagnosis and treatment. The following are two cases of neurosurgery provided by Peking Union Medical College Hospital. Molecular pathology plays an important role in differential diagnosis, clinical classification, prognosis and treatment options. What are the differences and connections between molecular pathology and traditional pathology? Ma Wenbin: I will give two patients. One is a 53-year-old man admitted to hospital in 2007. He has had a memory loss for half a year, and accompanied by sudden and severe headache within 3 days before admission. Hepatic calcification can be seen before surgery. The lesion, postoperative histopathology showed WHO grade III glioma (interstitial oligodendroglioma). Then we did a molecular pathological examination for him and found that he had three indicators positive: MGMT promoter region methylation, IDH gene mutation, and 1p/19q chromosome combined deletion. These molecular indicators suggest that patients are sensitive to chemoradiotherapy and have a longer survival period. Later, we performed radiotherapy + adjuvant chemotherapy on patients, and the effect was very good. The patient is still in a stable state. Another example is less pleasing. It was a 43-year-old woman admitted to the hospital in 2015. She had 9 months of paroxysmal fear and two weeks of fatigue and nausea before admission. Postoperative histopathology showed the same It is a WHO grade III glioma (anaplastic star megaloblastoma). We also performed a molecular pathological examination for her, and found that all three of the above mentioned indicators were negative, and the TERT gene promoter region mutation was positive. This suggests that the patient is not sensitive to radiotherapy and chemotherapy, and the disease progresses rapidly and the survival time is short. After a month of concurrent chemoradiotherapy, the patient's lesion recurred four months after surgery. After two-way adjuvant chemotherapy, the patient's headache began to increase at six months after surgery. From these two examples, we can see that molecular pathology has a very important significance for the differential diagnosis, clinical classification, prognosis and treatment options. This year, the current international authoritative guide "2016 World Health Organization (WHO) Central Nervous System Tumor Classification" is also the first to classify CNS tumors based on histological classification to identify molecular classification, thus establishing a new concept of CNS tumor diagnosis in molecular age. . What other molecular markers are mentioned? Ma Wenbin: Methylation of MGMT promoter region: Can predict whether patients with grade III and IV glioma can benefit from alkylating agent chemotherapy; 1p19q combined deletion: can be associated with low or low level of heterozygous deletion of 1p19q chromosome One of the indicators of glioma risk level and used as a marker for grade III anaplastic glioma typing. The morphology of gliomas carrying the 1p19q combined deletion is usually oligodendroglioma with a good prognosis, longer survival, and sensitivity to both radiotherapy and chemotherapy. IDH1/2 gene mutation and TERT promoter point mutation: IDH gene and TERT gene have more effects, and the presence or absence of IDH1/2 gene mutation can be used as one of the indicators for assessing the risk level of low-grade glioma. Patients carrying the IDH1/2 mutation are at low risk. IDH1/2 and TERT promoter region point mutations jointly define the molecular typing of glioma It is used for prognosis: grade IV glioblastoma (primary) or grade III anaplastic glioma with only TERT mutation, poor prognosis; gliomas carrying only IDH1/2 mutations mostly exhibit astrocyte morphology, The survival time is longer. At the same time, gliomas carrying TERT and IDH1/2 mutations often exhibit oligodendrocyte morphology, and the prognosis is the best. It is used to treat patients with malignant astrocytoma whose IDH mutation is more suitable for surgical resection, and total resection can prolong survival (neuro-oncology 2013); IDH mutant glioblastoma concurrent chemoradiotherapy is better than none IDH mutant glioblastoma (neuro-oncology 2014); Potential drugs: high-grade solid tumor subjects with IDH1 mutations including gliomas, oral AG-120 clinical study (clinicaltrial.gov); patients with recurrent grade II gliomas carrying IDH1 mutations, tumor-specific peptide vaccines Safety and immunogenicity studies (clinicaltrial.gov). Source: Medical Valley
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