ObjectiveTo evaluate the expression level of histone deacetylase 9 (HDAC9) in lung squamous cell carcinoma (LUSC) tissues, to analyze its correlations with clinicopathological characteristics and prognosis of LUSC patients, and to explore the effect it exerts on the proliferation of LUSC cells.MethodsThe expression level of HDAC9 was detected by immunohistochemistry staining (IHC), and its correlations with clinicopathological characteristics were analyzed by χ2 test. Survival analysis was performed using Kaplan-Meier method. Univariate and multivariate Cox proportional hazards model were employed to analyze independent predictors for overall survival (OS) of LUSC patients. CRISPR/dCas9 activation system was used to activate the transcription of HDAC9 gene in LUSC cell line EBC-1. CCK8 cell proliferation assay and colony formation test were performed to investigate the effect that transcriptional activation of HDAC9 exerts on the proliferation of LUSC cells.ResultsOf the 129 LUSC patients, 39 (30.2%) were in the HDAC9 low expression group and 90 (69.8%) were in the HDAC9 high expression group. The OS of the patients with HDAC9 high expression was shorter than that of patients with HDAC9 low expression (P=0.032). The expression level of HDAC9 was associated with tumor grade (P=0.035), primary tumor size (P=0.041), and lymph node metastasis (P=0.013). The expression level of HDAC9 (P=0.023), tumor grade (P=0.003), primary tumor size (P=0.003), and lymph node metastasis (P=0.002) were independent predictors for OS of LUSC patients. Transcriptional activation of HDAC9 promoted colony formation of LUSC cells and cell proliferating curves showed that LUSC cells with HDAC9 transcriptional activation proliferated faster than non-targeting cells (F=52.7, P=0.002).ConclusionLUSC patients with HDAC9 high expression have poorer prognosis than HDAC9 low expression ones. The expression level of HDAC9 is associated with tumor grade, primary tumor size, and lymph node metastasis, and is identified as an independent predictor for prognosis of LUSC. Transcriptional activation of HDAC9 promotes cell proliferation in LUSC. These results suggest that HDAC9 may serve as a promising biomarker for prognosis in LUSC.
摘要:目的:探讨PTTG的表达在非小细胞肺癌发生、发展中的作用及其与CMYC蛋白表达的关系。方法:应用免疫组化SP法检测PTTG、CMYC二种蛋白在44例非小细胞肺癌、20例肺良性病变组织和12例正常支气管粘膜上皮组织中的表达。结果:PTTG和CMYC蛋白在非小细胞肺癌组织中的表达明显高于肺良性病变组及癌旁组织,在TNM分期、淋巴结转移组间差别有统计学意义。非小细胞肺癌组织中PTTG与CMYC表达呈显著正相关。结论:提示PTTG和CMYC可能参与了非小细胞肺癌的发生和发展,可作为反映其生物学行为的指标。Abstract: Objective: To investigate the expression of PTTG and its relationship with expressions of CMYC protein in human nonsmall cell lung cancer (NSCLC).Methods: Immunohistochemical methods were applied to detect the expression of PTTG,CMYCproteins in 44 surgical specimens from NSCLC patients,20 pneumonic benign lesion and 19 normal bronchial epithelium. Results:There were high erexpressions of PTTG,CMYC in NSCLC tissues than inadjacent tissues and benign lesions.There were statistical relationships between their expressions and TNM stage,lymphnode metastasis.The expression of PTTG was positively correlated with CMYC. Conclusion: Overexpression of PTTG,CMYC may be related to human NSCLC,PTTG and CMYC play a cooperative role inthe process of NSCLC,all of them may be used as important indices for biologic behavior of NSCLC.
Objective To investigate the histological origin, diagnosis, differential diagnosis and treatment of thyroid carcinoma showing thymus-like differentiation (CASTLE). Methods Five patients with thyroid CASTLE were adopted by surgical resection and postoperative radiotherapy, and the CD5, CD117, CK5/6, P63, thyroid transcription factor-1 (TTF-1), carcino-embryonic antigen (CEA), calcitonin (CT), Ki-67, chromogranin A (CgA), thyrobolulin (Tg), peroxisome proliferator activated receptorγ (PPAR-γ), sodium iodide symporter (NIS), and thyroid stimulating hormone receptor (TSHR) were detected in tumor tissues by immunohistochemistry S-P method and v-raf murine sarcoma viral oncogene homolog B1 (BRAF)V600E gene and telomerase reverse transcriptase (TERT) promoter mutations were detected by DNA sequencing. Eight cases of poorly differentiated thyroid carcinoma and 6 cases of anaplastic thyroid carcinoma were adopted by comprehensive comparative analysis. Results Thyroid CASTLE tumor cells showed the positive expression of CD5, CD117, CK5/6 and P63, and the negative expression of TTF-1, CT, CgA, Tg, PPAR-γ, NIS and TSHR. There were partly positive expression for CK5/6, P63, TTF-1, CgA, Tg, NIS and TSHR, and negative expression for CD5 and CD117 in the poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. The BRAFV600E gene and TERT promoter mutations were not detected in thyroid CASTLE, and the BRAFV600E gene mutations were also not detected in the poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. Four cases of poorly differentiated thyroid carcinoma showed the TERT promoter mutations (4/8) included 3 cases with C228T and 1 case with C250T. Two cases of anaplastic thyroid carcinoma showed the TERT promoter mutations (2/6) included 1 case with C228T and 1 case with C250T. There was no recurrence and metastasis after 3–47 months (an average of 25.6 months) of followed-up in thyroid CASTLE patients. Conclusions The histological origin of thyroid CASTLE may be not related to the thyroid. There is important clinical value to combined detection of CD5, CD117, P63, TTF-1, Tg, NIS, and TSHR for the diagnosis and differential diagnosis of thyroid CASTLE. The further study still need for the diagnosis and differential diagnosis of thyroid CASTLE according to the detection of BRAFV600E and TERT promoter mutations.
ObjectiveTo explore the expression of alpha B-crystallin (CRYAB) in human gastric cancer tissue and the influence of chemotherapeutics on expression of CRYAB mRNA.Methods① The gastric cancer tissues and corresponding adjacent tissues of 76 patients underwent radical resection from April 2018 to March 2020 in The First Affiliated Hospital of Southwest Medical University and the Sichuan Mianyang 404 Hospital were collected, the expression of CRYAB protein in the gastric cancer tissues and corresponding adjacent tissues of 76 patients with gastric cancer were detected by immunohistochemistry SP technique. The relation between the expression of CRYAB protein and clinicopathologic features was analyzed. ② Twenty-one gastric tissues of patients accepted neoadjuvant chemotherapy and 26 gastric tissues of patients with no neoadjuvant chemotherapy in the The First Affiliated Hospital of Southwest Medical University were collected from November 2018 to March 2020, the expression of CRYAB mRNA was detected by real time-PCR.ResultsThe expression of CRYAB protein in gastric cancer tissues was positive in 51 cases (67.1%) and in the corresponding adjacent tissues was positive in 32 cases (42.1%), the positive rate was higher in gastric cancer tissues (χ2=9.581, P=0.002). The over-expression of CRYAB protein in the gastric cancer tissues was correlated with the TNM stage, Borrmann typing, degree of differentiation, lymph node metastasis, depth of invasion of the patients, and Lauren classification (P<0.05), but not correlated with the age, gender, tumor sitation, and diameter (P>0.05). The expression of CRYAB mRNA in the gastric cancer tissues with neoadjuvant chemotherapy was significantly higher than that in the gastric cancer tissues without neoadjuvant chemotherapy (t=8.37, P<0.001).ConclusionsThe over-expression of CRYAB protein is closely related to the invasion and progression of gastric cancer, they may be involved in the progression of gastric cancer and play a crucial role. Moreover, the expression of CRYAB mRNA increases after chemotherapy, it suggests that chemotherapy drugs can activate the self-protection mechanism of tumor cells to some extent, and influence the effect of chemotherapy by increasing expression of CRYAB protein.
ObjectiveTo detect expressions of Lgr5 and E-cadherin (E-cad) proteins in gastric cancer tissues and analyze their relationships with the clinicopathologic characteristics and prognosis of patients with gastric cancer.MethodsThe expressions of Lgr5 and E-cad proteins in the 69 patients with gastric cancer and adjacent normal gastric mucosa tissues were measured by the immunohistochemical SABC method, and the relationships between the Lgr5 or E-cad protein expression in the gastric cancer tissues and the clinicopathologic characteristics and the survival of patients with gastric cancer were analyzed.ResultsThe expressions of Lgr5 and E-cad proteins were positive in 60 cases (87.0%) and 30 cases (43.5%) of gastric cancer tissues, respectively, and in 5 cases (16.7%) and 30 cases (100%) of adjacent normal gastric mucosa tissues. There was a significant difference in the positive rate of Lgr5 or E-cad protein expression in the different tissues, respectively (Lgr5 protein: χ2=45.814, P<0.001; E-cad protein: χ2=11.249, P=0.001). The positive rates of Lgr5 and E-cad protein expressions in the gastric cancer were related to the degree of differentiation and the depth of invasion. Meanwhile the positive rate of Lgr5 protein expression in the gastric cancer tissue was also related to the lymph node metastasis and Helicobacter pylori infection, while the positive rate of E-cad protein expression was not related to these (P>0.05). The 5-year total survival time had no significant difference in the patients between with positive and with negative expressions of Lgr5 protein (χ2=1.819, P=0.117), which had a significant difference in the patients between with positive and with negative expressions of E-cad protein (χ2=5.814, P=0.016). The positive expression of Lgr5 was negatively correlated with that of E-cad (rs=−0.355, P=0.003).ConclusionsLgr5 protein may get involved in the mechanism of tumor invasion, lymph nodal metastasis, and low differentiation, while no relationship between the Lgr5 protein and prognosis has been confirmed. E-cad protein may get involved in the mechanism of tumor invasion and affect the prognosis of patients.
ObjectiveTo summarize clinicopathologic and immunophenotypic features of hepatic epithelioid angiomyolipoma (HEAML) and to explore its diagnostic and differential diagnostic methods.MethodThe clinical and imaging manifestations, pathological morphology and immunohistochemical features of 5 patients with HEAML from August 2011 to December 2017 in this hospital were retrospectively analyzed.ResultsThere were 2 males and 3 females in the 5 patients with HEAML, aged 38–64 years with an average age of 50 years. There were 2 cases of the left lobe tumors and 3 cases of the right lobe tumors. Three cases were diagnosed as the hepatocellular carcinoma and the other two cases were diagnosed as the hepatic hamartoma and (or) hemangioma by the preoperative imaging examination. The diameter of tumors ranged from 1.5 cm to 7.0 cm, with an average of 3.6 cm. Microscopically, the tumors were composed of more epithelioid smooth muscle cells, parenchyma vessels and a small amount of fat. The immunohistochemical results showed that the melan-A, HMB45, and SMA were positive, while the HepPar-1, AE1/AE3, EMA, CD117, Dog-1, CD10, CgA, Syn, and Desmin were negative. The Ki-67 proliferation index was 2%–10%. The patients were all alive without the tumor recurrence after following up for 2–76 months with an average of 31.4 months.ConclusionsHEAML is a rare primary mesenchymal tumor of liver, which should be misdiagnosed for other benign or malignant tumors for influencing clinical treatment. Diagnosis and differential diagnosis can be made by histopathology and immunohistochemical staining.
ObjectiveTo investigate the correlation between expression of stromal interaction molecule 1 (STIM1) and tumor malignant degree or lymph node metastasis in patients with gastric cancer. MethodsA total of 83 patients with gastric cancer treated in the Affiliated Hospital of Southwest Medical University and Sichuan Mianyang 404 Hospital from October 2018 to April 2021 were collected. The expression of STIM1 protein in the gastric cancer tissues and the corresponding adjacent normal gastric tissues was detected by immunohistochemistry method. Meanwhile the correlation between the expression of STIM1 protein and clinicopathologic features or postoperative lymph node status of the patients with gastric cancer was analyzed. ResultsThe positive rate of STIM1 protein expression in the gastric cancer tissues was 95.2% (79/83), including 62 (74.7%) patients with high expression (STIM1 scoring 5–7) and 21 (25.3%) patients with low expression (STIM1 scoring 2–4), which in the corresponding adjacent normal gastric tissues was 41.0% (34/83), the difference was statistically significant (χ2=58.078, P<0.001). The expression of STIM1 protein was not related to gender, age, and tumor size of the patients with gastric cancer (P>0.05), while the proportions of the patients with high expression of STIM1 protein in the gastric cancer patients with low/undifferentiated tumor, T3+T4 of infiltration depth, TNM stage Ⅲ, and lymph node metastasis were higher than those with high/medium differentiation (χ2=11.052, P=0.001), T1+T2 of infiltration depth (χ2=24.720, P<0.001), TNM stage Ⅰ+Ⅱ (χ2=9.980, P=0.002), and non-lymph node metastasis (χ2=6.097, P=0.014). The expression intensity of STIM1 protein was positively correlated with the number of lymph node metastasis (r=0.552, Z=–3.098, P=0.002) and the rate of lymph node metastasis (r=0.561, Z=–6.387, P<0.001). ConclusionsPositive rate of STIM1 protein expression in gastric cancer tissues is relatively high. STIM1 protein expression in gastric cancer tissue is closely related to tumor malignancy and lymph node metastasis, so it might play an important role in progression of gastric cancer.
Objective To analyze the expression differences of FoxP3 protein in papillary thyroid carcinoma (PTC) and nodular goiter, and to explore the correlation between FoxP3 and the clinicopathological characteristics of PTC patients and the therapeutic dose of 131I. Methods Immunohistochemical method was used to detect the expression of FoxP3 protein in 128 cases of PTC tissues (42 cases were treated with 131I after operation) and 20 cases of nodular thyroid tissues, and the relationship between it and the clinicopathological characteristics of PTC patients and the dose of 131I treatment was also analyzed. Results The positive rate of FoxP3 protein expression in PTC tissues was 46.09%, which was higher than that in nodular goiter tissues (0.00%), and the difference was statistically significant (P<0.001). The expression of FoxP3 protein in PTC was correlated with gender, extraglandular invasion and tumor diameter (P values were 0.041, 0.039, and 0.007, respectively), but had no correlation with age, capsular invasion, TNM staging, lymph node metastasis, and distant metastasis (P>0.05). The results of binary logistic regression analysis suggest that tumor diameter was an independent risk factor affecting FoxP3 protein expression [OR=0.389, 95%CI (0.180, 0.840), P=0.016]. By drawing the receiver operating characteristic (ROC) curve, it was shown that the area under the curve (AUC) was 0.643 when the tumor diameter was 1.05 cm, the sensitivity to predict the increase in FoxP3 protein expression was 64.41%, and the specificity was 57.97%, P=0.006. Among 42 patients with PTC who underwent 131I treatment after surgery, the therapeutic dose of 131I was related to the expression of FOXP3 protein (P=0.031). It was shown that patients with positive expression of FoxP3 protein were given more dose of 131I after surgery. Conclusions The positive rate of FoxP3 protein expression in PTC is higher than that of nodular goiter. Its high expression means that the patient has poor pathological characteristics and larger 131I treatment dose, suggesting that FoxP3 may be involved in the malignant progression of PTC.
Objective To investigate expressions of EphA2 and EphrinA1 in invasive ductal carcinoma of breast and to explore their clinical significances. Method The protein and mRNA expressions of EphA2 and EphrinA1 in 30 breast fibroma tissues, 30 breast cystic hyperplasia tissues, and 100 invasive ductal carcinoma of breast tissues were detected by immunohistochemistry andin situ hybridization respectively, and correlation between them and relations between their expressions in invasive ductal carcinoma of breast tissues and clinicopathologic factors were analyzed. Results ① The results of the immunohistochemistry andin situ hybridization tests showed that the protein and mRNA expressions of EphA2 and EphrinA1 in the invasive ductal carcinoma of breast tissues were significantly higher than those in the breast fibroma tissue (P<0.001) and breast cystic hyperplasia tissue (P<0.001). ② The positive expressions of EphA2 and EphrinA1 protein and mRNA were associated with the lymph node metastasis, histological grade, and TNM stage (P<0.05), in other words, which in the invasive ductal carcinoma of breast patients with lymph node metastasis, high histological grade, and high TNM stage were higher. However, which were not associated with the age and the tumor diameter (P>0.05). ③ The positive protein expressions or positive mRNA expressions in the invasive ductal carcinoma of breast tissues all had positive correlations between the EphA2 and the EphrinA1 (protein:rs =0.999,P<0.01; mRNA:rs =0.942,P<0.01). Conclusions EphA2 and EphrinA1 might be involved in carcinogenesis and development procedures of invasive ductal carcinoma of breast. Combined detection of EphA2 and EphrinA1 could help to predict clinical and pathologic characteristics of invasive ductal carcinoma of breast. They might provide a new target for clinical medication, prognosis, and targeted therapy.
Objective To investigate the expressions and clinical significance of Notch-2 protein and Numb protein in papillary thyroid carcinoma (PTC). Methods PTC tissues and its para-cancerous tissues of 50 patients with PTC who treated in The Affiliated Hospital of Inner Mongolia University for Nationalities from Mar. 2014 to Mar. 2017 were retrospectively collectied, to detect the expressions of Notch-2 protein and Numb protein by immunohistochenmical method. Results ① Expressions of Notch-2 protein and Numb protein in PTC tissues and para-cancerous tissues: the positive-expression rate of Notch-2 protein in PTC tissues was 82.00% (41/50), which was higher than that of para-cancerous tissues〔18.00% (9/50)〕, the difference was statistically significant (χ2=40.960, P<0.001). The positive-expression rate of Numb protein in PTC tissues was 66.00% (33/50), which was higher than that of para-cancerous tissues 〔0 (0/50) 〕, the difference was statistically significant (χ2=49.254, P<0.001). ② The relationship between expression of Notch-2 protein and expression of Numb protein in PTC tissues: there was a positive correlation between expressions of Notch-2 protein and Numb protein in PTC tissues (rs=0.323, P=0.022). ③ The relationship between expressions of Notch-2 protein and Numb protein in PTC tissues and clinicopathological features of the PTC patients: the expression of Notch-2 protein in PTC tissues was not significantly correlated with gender, age, tumor diameter, capsule infiltration, cervical lymph node metastasis, and TNM staging (P>0.05). The expression of Numb protein in PTC tissues was not significantly correlated with gender, age, tumor diameter, and capsule infiltration (P>0.05), but was significantly correlated with cervical lymph node metastasis and TNM staging (P<0.05), the positive rates of Numb protein in patients of staging Ⅲ+Ⅳ group and cervical lymph node metastasis group were lower than those of patients in staging Ⅰ+Ⅱ group and non-cervical lymph node metastasis group. Conclusion The positive-expression rate of Notch-2 protein and Numb protein in PTC tissues are higher than those of para-cancerous tissues, and there is a positive correlation between them in PTC tissues, suggesting that there may be a synergistic effect in the course of PTC progression.