Histology and histopathology Vol.34,nº11 (2019)
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- PublicationOpen AccessPrognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer.(Celular e Histiologia Universidad de Murcia, Departamento de Biologia, 2019) Zhu, Wang-Yu; Hu, Xiao-Fei; Fang, Ke-Xin; Kong, Qiong-Qiong; Cui, Ri; Feng, Hai; He, Jian-Ying; Zhang, Yong-kui; Le, Han-BoIntroduction. The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct. Material and methods. Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations. Results. Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P<0.001 and <0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and <0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P<0.0001 and 0.0009, and P<0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF- 1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022). Conclusion. The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.
- PublicationOpen AccessHigh expression of DEK is associated with poor prognosis in hepatocellular carcinoma.(Celular e Histiologia Universidad de Murcia, Departamento de Biologia, 2019) Lee, Soo Yeon; Jung, Wonkyung; Lee, Jinhwan; Kim, Aeree; Kim, Han Kyeom; Kim, Baek-HuiDEK is an oncogene that has been identified as part of the DEK-CAN fusion gene. DEK plays a role in carcinogenesis through WNT signaling and induces cell proliferation through cyclin-dependent kinase signaling. DEK overexpression has been reported in HCC, but the clinical significance is unclear. This study enrolled 221 cases of HCC. The expression of DEK protein was evaluated by immunohistochemical staining. Cdk4, cyclin D1, Wnt10b, E-cadherin, and β-catenin were also immunohistochemically stained and analyzed for correlation. The association of clinicopathologic factors with DEK expression was analyzed. DEK expression was observed in 44.8% (99/221) of cases. DEK expression showed a statistical association with clinicopathologic factors, including Edmondson-Steiner grade, presence of vascular emboli, and multiplicity (p<0.05). Among the other IHC markers, the expression of cdk4 was correlated with DEK expression (p<0.05). Patients with high DEK expression showed a significantly lower overall survival rate (p=0.006). However, the disease-free survival rate did not differ significantly. In addition, in a Cox regression model analysis, DEK expression was an independent prognostic factor. In summary, high expression of DEK was observed in HCC and was associated with poor prognostic marker expression and poor prognosis.
- PublicationOpen AccessUnique expression profiles of mucin proteins in interstitial pneumonia-associated lung adenocarcinomas(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Tateishi, Yoko; Kataoka, Toshiaki; Okudela, Koji; Nakashima, Yu; Mitsui, Hideaki; Matsumura, Mai; Umeda, Shigeaki; Arai, Hiromasa; Baba, Tomohisa; Suzuki, Takehisa; Koike, Chihiro; Tajiri, Michihiko; Takemura, Tamiko; Ogura, Takashi; Masuda, Munetaka; Ohashi, KenichiIn order to clarify idiopathic interstitial pneumonia (IIP)-associated lung adenocarcinoma (LADC), we herein focused on the expression profiles of mucin proteins, the most common cellular differentiation markers. The expression of the mucin (MUC) 1, MUC2, MUC3B, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC9, and MUC21 proteins was examined immunohistochemically and their levels were semi- quantified in 80 IIP-associated LADCs and 106 non-IIP LADCs. LADCs were divided into low and high expressers based on thresholds obtained from the receiver operating characteristic (ROC) curves of each mucin protein. Low expressers of MUC1, MUC7, and MUC21 and high expressers of MUC4, MUC5AC, MUC5B, and MUC9 were dominant in the IIP group. Multivariate analyses confirmed that the correlations between mucin expression profiles and IIP-associated LADCs were independent of putative confounding factors, such as smoking, gender, histological types, and cytological types. Thus, the expression profiles of these mucin proteins significantly differed between the IIP and non-IIP groups. IIP-associated LADCs appear to have unique cellular differentiation features and they may develop through a distinct histogenetic pathway. This is the first study to demonstrate that IIP-associated LADCs have unique mucin expression profiles.
- PublicationOpen AccessA sexy approach to pacemaking: differences in function and molecular make up of the sinoatrial node(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Doris, Ursula; Kharche, Sanjay; Petkova, Maria; Borbas, Balint; Logantha, Sunil Jit R.J.; Fedorenko, Olga; Maczewski, MIchal; Mackiewicz, Urszula; Zhang, Yu; Chahal, Anwar; D’Souza, Alicia; Atkinson, Andrew J.; Dobrzynski, Halina; Yanni, JosephBackground. Functional properties of the sinoatrial node (SAN) are known to differ between sexes. Women have higher resting and intrinsic heart rates. Sex determines the risk of developing certain arrhythmias such as sick sinus syndrome, which occur more often in women. We believe that a major contributor to these differences is in gender specific ion channel expression. Methods. qPCR was used to compare ion channel gene expression in the SAN and right atrium (RA) between male and female rats. Histology, immunohistochemistry and signal intensity analysis were used to locate the SAN and determine abundance of ion channels. The effect of nifedipine on extracellular potential recording was used to determine differences in beating rate between sexes. Results. mRNAs for Ca v1.3, Kir3.1, and Nkx2-5, as well as expression of the L-Type Ca 2+ channel protein, were higher in the female SAN. Females had significantly higher intrinsic heart rates and the effect of nifedipine on isolated SAN preparations was significantly greater in male SAN. Computer modelling using a SAN cell model demonstrated a higher propensity of pacemaker-related arrhythmias in females. Conclusion. This study has identified key differences in the expression of Ca v 1.3, K ir 3.1 and Nkx2-5 at mRNA and/or protein levels between male and female SAN. Cav1.3 plays an important role in the pacemaker function of the SAN, therefore the higher intrinsic heart rate of the female SAN could be caused by the higher expression of Ca v 1.3. The differences identified in this study advance our understanding of sex differences in cardiac electrophysiology and arrhythmias.
- PublicationOpen AccessCalcitonin gene related peptide gene-modified rat bone mesenchymal stem cells are effective seed cells in tissue engineering to repair skull defects(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Yu, Xijiao; Liu, Shuang; Chen, Xue; Du, Yanmei; Yin, Xiaochun; Du, Yi; Li, ShuThe study is to verify whether Calcitonin gene related peptide (CGRP) gene-modified rat bone mesenchymal stem cells (BMSCs) are promising seed cells with great potential to repair bone defect. A recombinant lentiviral vector overexpressing CGRP peptide, pLenO-DCE-CGRP, was constructed and transfected into rBMSCs to obtain stable CGRP expression. Differently transfected rBMSCs: CGRP- modified rBMSCs (CGRP group), empty vector- modified rBMSCs (Vector group) and normal rBMSCs (Control group) were transferred to collagen scaffold to repair rat skull defects (n=6). Skull specimens were obtained at 4 and 8 weeks after operation. Expressions of osteogenesis-related indexes OCN (osteocalcin) and BMP-2 (Bone morphogenetic protein-2) were detected by immunohistochemistry and western blotting. Histological observation, Masson trichrome staining and Micro-computed tomography (Micro-CT) were applied to evaluate defect repair. Tartrate-resistant acid phosphatase (TRAP) was applied to observe bone remodeling at 4 weeks. PGP9.5 was detected to observe nerve fibers formation at 8 weeks. Osteogenic markers OCN and BMP-2 were significantly higher in CGRP -modified BMSCs at 4 weeks, compared with the vector and control groups. Few TRAP-positive expressions and scaffolds were observed in the CGRP group. More new bone formation and mineralization in defects were observed in the CGRP group at 4 and 8weeks. Many PGP9.5-positive expressions were found in the CGRP group. CGRP promoted osteogenic differentiation of BMSC and scaffold resorption in vivo. Repair effect of CGRP group was significantly better than the other two groups. CGRP gene-modified BMSCs are effective seed cells in tissue engineering to repair bone defects.