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Objective:To investigate the clinicopathologic features and molecular genetics characteristics of sinonasal tract mucosal malignant melanomas(STMMMs)in elderly patients.Methods:The clinicopathological features, immunohistochemical features and BRAF, C-KIT, NRAS mutations of STMMM in ten elderly patients were retrospectively analyzed.Results:Among the 10 patients, 5 were female and 5 were male.The patients were aged 65-81 years, with an average age of(72.5 ± 8.5)years.The lesions in 7 cases were located in the nasal cavity and paranasal sinuses, and in the other 3 cases were located in the nasopharynx.The morphologies of tumor cells under microscope was complex and diverse, showing plasma cell-like, rhabdomyoblast-like, small cell-like, epithelial-like, and spindle cell-like morphologies.Immunohistochemically, HMB-45 and S-100 were generally positive in 10 cases, and the positive rate of Melan A was 70.0%.The genes detection data showed no mutations in BRAF or NRAS genes in all the 10 cases, while C-KIT exon 11 c. 1666_1667insA mutation was found in one case, and the remaining 9 cases were wild-type for C-KIT.All the 10 cases were followed up for 4~50 months.Three cases survived so far.Conclusions:STMMM in elderly patients are rare and easy to be misdiagnosed.Immunohistochemistry and genetic testing provide guidance for accurate diagnosis and targeted therapy.
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Objective To explore the molecular genetic characteristics of primary and recurrent glioblastomas (GBMs) from the same patient in vivo, primary glioma stem cells cultured in vitro, and patient-derived xenograft (PDX). Methods (1) The primary and recurrent GBM specimens from one patient during surgical resection were collected; and the expressions of glial fibrillary acidic protein (GFAP), nestin and Ki-67 were detected by immunohistochemical staining; the methylation of O6-methylguanine DNA methyltransferase (MGMT) gene, mutation of isocitrate dehydrogenase (IDH) gene and amplification of epidermal growth factor receptor (EGFR) gene were analyzed. (2) The primary and recurrent GBM stem cells were cultured in vitro and named as SU5-1 and SU5-2 cells, respectively; the expressions of nestin and CD133 were detected by immunohistochemical staining; GFAP expression was detected by immunohistochemical staining after induced differentiation, and the growth curve was detected by CCK-8 assay; Transwell invasion assay was used to detect the invasion ability; cell resistance to temozolomide (TMZ), carboplatin (CBP), cisplatin (DDP) and adriamycin (ADM) was detected by CCK-8 assay; the protein expression of programmed death receptor-ligand 1 (PD-L1) was detected by Western blotting. The rate of PD-L1 positive cells was detected by flow cytometry; genetic testing analysis was as above. (3) The primary and recurrent in situ PDX models in nude mice were established, and the expressions of nestin, GFAP and Ki-67 were detected by immunohistochemical staining. Results (1) As compared with the primary GBM, the recurrent GBM had significantly higher percentages of Ki-67 and nestin positive cells, while statistically lower percentage of GFAP positive cells (P<0.05); genetic analysis showed that there was no mutation in IDH gene in the primary GBM tissues and recurrent GBM tissues; the MGMT gene in the primary GBM tissues was methylated and EGFR gene was not amplified, while the MGMT gene in recurrent GBM tissues was demethylated and EGFR gene amplification was positive. (2) Both SU5-1 and SU5-2 cells expressed nestin and CD133, and GFAP was expressed after induced differentiation; the growth curve showed that the proliferation of SU5-2 cells started earlier than that of SU5-1 cells, the two were equal on the 3rd, 4th, and 5th d, and the proliferation of SU5-1 cells was faster than that of SU5-2 cells from the 6th d; the invasion ability of SU5-2 cells was statistically stronger than that of SU5-1 cells (P<0.05); the inhibition rates of SU5-2 cells treated with 5, 10, and 15 mmol/L CBP, 0.3125, 1.25, and 5 mmol/L DDP, 0.5 and 2 mmol/L ADM, and 125 and 500 mmol/L TMZ were significantly lower than those of SU5-1 cells treated with the same concentrations and same drugs (P<0.05); the protein expression of PD-L1 in SU5-2 cells was higher than that in SU5-1 cells; the positive rate of PD-L1 in SU5-2 cells was statistically higher than that in SU5-1 cells (P<0.05); the results of genetic analysis were consistent with those of the primary and recurrent GBM samples. (3) As compared with those in the primary PDX model, the nestin and Ki-67 expressions were significantly higher and GFAP expression was significantly lower in the recurrent PDX model (P<0.05); the results of genetic analysis were consistent with those of the primary and recurrent GBM samples. Conclusions Genetic differences are detected between primary and recurrent GBMs; recurrent GBM has stronger invasive capacity and multi-drug resistance. The primary stem cells derived from surgical specimens and corresponding PDX models could replicate the molecular genetic characteristics of original tumors, which provide a reliable experimental platform for both tumor translation researches and screening of molecular therapeutic targets.
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Objective To evaluate the correlation of CT enhancement parameters with Fuhrman grade in T1 (≤7 cm) clear cell renal carcinoma(ccRCC).Methods From September 2011 to November 2017,102 post-operation cases in our hospital proven to be T1 ccRCC were retrospectively analyzed.There were 71 males and 31 females,with a mean age of (59.1 ± 12.7)years (26 ～79 years),mean body mass index(BMI) of (24.0 ± 2.8)kg/m2 (14.3 ～ 31.6 kg/m2).Tumors of 55 patients were in left kidneys,47 in right kidneys.Fuhrman grade 1 and 2 were defined as low-grade group,meanwhile high-grade group included grade 3 and 4.There were 46 males and 21 females in low-grade group,with a mean age of (59.0 ± 13.2) years,mean BMI of (24.0 ± 2.9) kg/m2.In high-grade group,there were 25 males and 10 females,with a mean age of (58.8 ± 11.8) years,mean BMI of (24.2 ± 2.7) kg/m2.The maximum diameter and tumor enhancement value (TEVX),relative enhancement value (REVX) were measured and calculated.In arterial phase,X =1;in venous phase X =2.The total consumption amount of iodine was recorded.Comparisons of maximum diameter,TEV1,TEV2,REV1,REV2 and the total consumption of iodine between the two different groups were performed.The ROC curves of TEV1,TEV2,REV1,and REV2 were drawn to predict the grade of tumors..Results The TEV1 [(146.1 ± 29.1) HU vs.(100.2 ± 32.1) HU],TEV2 [(98.2 ± 22.9) HU vs.(75.6 ± 25.7) HU],REV1 (1.12 ± 0.24 vs.0.70 ± 0.16),REV2(0.67 ± 0.17 vs.0.54 ± 0.18) between low-grade group and high-grade group had statistical difference (P ＜ 0.05).There was no significant difference in the maximum diameter[(41.8 ± 15.4)mm vs.(45.3 ± 17.0)mm] and the total consumption of iodine [(33.3 ± 5.0)g vs.(34.2 ± 4.4)g] between the two groups (P ＞ 0.05).The area under ROC curve of TEV1,TEV2,REV1 and REV2 were 0.856,0.755,0.901 and 0.728,respectively.REV1 had the highest distinguish efficiency and the best critical value was 0.93.Conclusions The enhancement parameters of T1 ccRCC could contribute to predicting the Fuhrman grade.When the REV1 ≤0.93,the tumor tended to be high-grade tumor(Fuhrman grade 3-4).