Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Objective:To investigate the immunohistochemical expression pattern of phosphatase and tensin homolog deleted on chromosome ten(PTEN)protein with chromosome 10 deletion in endometrioid carcinoma(EEC)and its relationship with DNA mismatch repair(MMR)protein.Methods:A total of 121 patients diagnosed with EEC,endometrial atypical hyperplasia/endometrial intraepithelial neoplasia(EAH/EIN),and normal endome-trium due to uterine fibroid resection at Hubei Cancer Hospital Affiliated to Tongji Medical College of Huazhong U-niversity of Science and Technology from May 14,2019 to June 7,2023 were selected as the study subjects,inclu-ding 84 patients in the EEC group,17 patients in the EAH/EIN group,and 20 patients in the control group.Immu-nohistochemical was used to detect the expression patterns and differences of PTEN and MMR in endometrial tis-sues of three groups,and the differences in abnormal expression of PTEN protein in EEC between MMR protein deficient(MMRd)group and non-deficient(MMRp)group were compared.Results:①The expression of PTEN protein in 121 endometrial glandular epithelial cells includes four patterns:normal expression,negativeexpression,reduced expression,and heterogeneous expression.②The abnormal expression rates of PTEN protein in the EEC and EAH/EIN groups(84.5％and 94.1％)were higher than those in the control group(10.0％);The ex-pression rates of MMRd protein in the EEC group and EAH/EIN group(35.7％and 35.3％)were higher than those in the control group(0％),and the above differences were statistically significant(P＜0.05).③The abnor-mal expression rate of PTEN in the MMRd group was 96.7％,which was higher than that in the MMRp group(96.7％vs.77.8％,P=0.048).④In the EEC group,with normal and abnormal expression of PTEN protein,there was no statistically significant difference in the comparison of different pathological grades,muscle infiltration depth,lymph node metastasis,and lymphatic vessel invasion between the MMRd group and the MMRp group(P＞0.05).Conclusions:Identifying the abnormal expression pattern of PTEN protein and combining it with MMR protein detection can help identify endometrial dysplasia,and there may be a correlation between PTEN and MMR protein expression in EEC.The abnormal expression of PTEN may not have a clear impact on the biological behavior of MMRd expressing EEC.

Objective:To investigate the immunohistochemical expression pattern of phosphatase and tensin homolog deleted on chromosome ten(PTEN)protein with chromosome 10 deletion in endometrioid carcinoma(EEC)and its relationship with DNA mismatch repair(MMR)protein.Methods:A total of 121 patients diagnosed with EEC,endometrial atypical hyperplasia/endometrial intraepithelial neoplasia(EAH/EIN),and normal endome-trium due to uterine fibroid resection at Hubei Cancer Hospital Affiliated to Tongji Medical College of Huazhong U-niversity of Science and Technology from May 14,2019 to June 7,2023 were selected as the study subjects,inclu-ding 84 patients in the EEC group,17 patients in the EAH/EIN group,and 20 patients in the control group.Immu-nohistochemical was used to detect the expression patterns and differences of PTEN and MMR in endometrial tis-sues of three groups,and the differences in abnormal expression of PTEN protein in EEC between MMR protein deficient(MMRd)group and non-deficient(MMRp)group were compared.Results:①The expression of PTEN protein in 121 endometrial glandular epithelial cells includes four patterns:normal expression,negativeexpression,reduced expression,and heterogeneous expression.②The abnormal expression rates of PTEN protein in the EEC and EAH/EIN groups(84.5％and 94.1％)were higher than those in the control group(10.0％);The ex-pression rates of MMRd protein in the EEC group and EAH/EIN group(35.7％and 35.3％)were higher than those in the control group(0％),and the above differences were statistically significant(P＜0.05).③The abnor-mal expression rate of PTEN in the MMRd group was 96.7％,which was higher than that in the MMRp group(96.7％vs.77.8％,P=0.048).④In the EEC group,with normal and abnormal expression of PTEN protein,there was no statistically significant difference in the comparison of different pathological grades,muscle infiltration depth,lymph node metastasis,and lymphatic vessel invasion between the MMRd group and the MMRp group(P＞0.05).Conclusions:Identifying the abnormal expression pattern of PTEN protein and combining it with MMR protein detection can help identify endometrial dysplasia,and there may be a correlation between PTEN and MMR protein expression in EEC.The abnormal expression of PTEN may not have a clear impact on the biological behavior of MMRd expressing EEC.

Syncytial giant cells (SGCs) are epithelial giant cells with multiple uniform and similar nuclei. Clear cell renal cell carcinoma (ccRCC) with SGCs is a rare microscopic morphology. A 70-year-old man was admitted to hospital with multiple nodules in both lungs found by chest CT examination 2 weeks before. A left renal carcinoma with lung metastasis was considered by PET-CT. Cytoreductive nephrectomy was performed, and postoperative pathological diagnosis confirmed ccRCC with SGCs of the left renal. Combined immunotherapy and targeted therapies were administered. There was no disease progression during follow-up period of 28 months.

Purpose To analyze the expression of TRPS1 protein in breast cancer and lung cancer and its difference,and to explore the diagnostic value of TRPS1 protein in differential diagnosis between lung metastasis from breast cancer and prima-ry lung cancer.Methods A total of 369 cases of breast canc-er,57 cases of primary lung cancer(23 cases of surgical resec-tion samples,34 cases of biopsy samples),and 35 cases of lung metastases from breast cancer(3 cases of surgical resection sam-ples,32 cases of biopsy samples)were collected.Immunohisto-chemical EnVision method was used to detect the expression of TRPS1 protein in all cases and to analyze its expression differ-ences.Results TRPS1 protein was expressed in 369 cases of breast cancer,of which 93.2％cases showed diffusely strongly positive expression(≥95％ strongly positive expression in tumor cell nucleus),6.8％ cases showed heterogeneous expres-sion of tumor cells,and the tumor types were mainly breast cancer with sweat gland differentiation and metaplastic cancer.Among 57 cases of primary lung cancer,28.1％of cases were negative for TRPS1,70.2％ of cases showed heterogeneous ex-pression,manifested as varying degrees of nuclear staining or only focal nuclear staining,and heterogeneous expression was dominant in different histological types including adenocarcino-ma,squamous cell carcinoma,and neuroendocrine carcinoma.In addition,TRPS1 was observed to be diffusely strongly positive in one(1.7％)lung adenocarcinoma biopsy sample.Among 35 cases of lung metastases from breast cancer,including surgical resection samples and biopsy samples,100％cases showed dif-fusely strongly positive expression of TRPS1.The expression of TRPS1 in lung metastasis of breast cancer and primary lung cancer was significantly different(P＜0.001).Conclusion TRPS1 protein is a highly sensitive and specific biomarker for breast cancer,but it can still be expressed in other tumors such as lung cancer,and it is also observed that TRPS1 is expressed to varying degrees in various histological types of lung cancer,which has certain diagnostic value in differentiating lung metas-tases from primary lung cancer in breast cancer,but it cannot be used as a single diagnostic marker,especially in small biopsy tissues of lung nodules.Therefore it is necessary to use multiple biomarkers to comprehensively determine the source of metasta-ses to improve the diagnostic accuracy,so as to guide follow-up clinical treatment.

Objective To investigate the clinicopathological characteristics of colorectal cancer patients with different mismatch repair (MMR) statuses and their correlation with KRAS/NRAF/BRAF (KNB) gene mutations. Methods The clinicopathological data of 477 patients with colorectal cancer were collected, and MMR, microsatellite instability (MSI), and KNB status were detected via immunohistochemistry (IHC), PCR–capillary electrophoresis, and next-generation sequencing (NGS), respectively. The clinicopathological features of patients with different MMR statuses and correlations with KNB mutations were analyzed. Results Compared with the patients in the pMMR group, the patients in the classical dMMR group were younger, included more females, and exhibited more tumors in the right colon, mostly mucinous adenocarcinoma and poorly differentiated tumors (all P<0.05). The tumors in the nonclassical dMMR group were commonly found in the right colon and were prone to special histologic types (all P<0.05). MLH1-PMS2 codeletion, BRAF mutation, and KRAS G13 codon mutation were common in patients in both the classical and the nonclassical dMMR groups (both P<0.05). The results of MMR IHC (100%) were highly consistent with those of MSI PCR (99.1%). Patients in the classical dMMR group with KRAS mutations were younger, included more males, and were prone to specific histologic types, but distant metastasis was rare (all P<0.05). Conversely, lymph node metastasis was rare in patients in the nonclassical dMMR group with KRAS mutations (P=0.005). The mutation rate of the MSH6 gene was relatively high in the nonclassical dMMR group (P=0.002), and all patients presented complete deletion of MLH1-PMS2 combined with nonclassical expression of MSH6 (100%). Five patients with medullary carcinoma components had complete deletions of MLH1-PMS2. Among the five patients, three had combined nonclassical expression of MSH2/MSH6. Two of the three patients carried the MSH6 gene c.3261 locus mutation. Conclusion The clinicopathologic features of patients with classical/nonclassical dMMR colorectal cancer differ from those of patients with pMMR, and MMR IHC could be used to predict effectively the MSI status. The clinicopathologic features differ between classical and nonclassical dMMR colorectal cancer patients with KRAS mutations, but both groups present codeletion of MLH1-PMS2, BRAF mutation, and KRAS G13 codon mutation. In patients with nonclassical dMMR, complete deletion of MLH1-PMS2 combined with nonclassical expression of MSH6 is common. Mutations in the MSH6 gene may play a key role in the development of colorectal cancer with medullary carcinoma components.

Objective To investigate the clinicopathological characteristics and treatment effect of patients with non-small cell lung cancer (NSCLC) and uncommon epidermal growth factor receptor (EGFR) gene mutations. Methods Real-time fluorescence quantitative PCR was used to detect the mutation of EGFR in 674 samples of patients with NSCLC.The correlation between uncommon EGFR mutations and clinicopathological characteristics was analyzed. Results The EGFR mutation rate was 47.92%, of which the incidence of uncommon EGFR mutations was 5.19%, showed the presence of ex18 G719 A/S/C (G719X)(1.63%), ex20ins (1.04%), ex21 L861Q (0.74%), and compound mutations (1.78%).Correlation analysis showed that uncommon EGFR mutations were more common in women, non-smokers, patients with high-medium differentiation and adenocarcinoma, and patients were more prone to brain and bone metastasis (all P < 0.05).NSCLC with uncommon EGFR mutations showed no significant differences in clinical and pathological features compared with those with common sensitive mutations (all P > 0.05).Follow-up information was available on 31 patients, with a median follow-up time of 10 months, of which 23 were in advanced stage.Among eight patients with G719X mutation in late stage, seven patients used EGFR tyrosine kinase inhibitor (EGFR TKIs)(five of them used afatinib) in the first line and had a median PFS of 12 months; one patient received chemotherapy with pemetrexed and carboplatin and had PFS of seven months, which was lower than that of the TKI group.Among four patients with L861Q mutation in late stage, one patient was untreated and the three remaining were treated with TKI in the first line and had a median PFS of eight months.The patient who was treated with afatinib and bevacizumab was still stable after 11 months of follow-up.Two patients with EGFR ex20ins in advanced stage were treated with chemotherapy and bevacizumab.Nine patients with compound mutations in advanced stage were treated with TKI; among which, five patients harboring T790M compound mutations were treated with third-generation TKI and had a median PFS of more than 10 months. Conclusion The correlation between specific uncommon EGFR mutation and clinical pathological characteristics varies.For advanced patients with uncommon EGFR mutations (except for ex20ins), TKI is generally chosen as the first-line clinical treatment.Afatinib is recommended for advanced NSCLC patients with G719X and L861Q mutations.Third-generation TKI has significant efficacy in patients with complex mutations containing T790M.

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.