Histology and histopathology Vol.35, nº7 (2020)

Ir a Estadísticas

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https://hdl.handle.net/10201/123213

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    Overexpression of YES1 is associated with favorable prognosis and increased platinum-sensitivity in patients with epithelial ovarian cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Zhou, Yun; Chen, Ping; Huang, Qidan; Wan, Ting; Jiang, Yinan; Jiang, Senwei; Yan, Sumei; Zheng, Min
    Aims. The prognostic application of YES1 in epithelial ovarian cancer (EOC) is currently unclear. We aimed to investigate the expression of YES1 and its correlation with survival outcome in patients with EOC. Methods. A retrospective study of patients diagnosed with EOC at the Cancer Center, Sun Yat-Sen University, Guangzhou, China between 2002 and 2013 was conducted. The immunohistochemical expression of YES1 was assessed using tissue microarray. Survival rates were analyzed by the Kaplan-Meier method and were compared between groups using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results. A total of 132 patients with EOC were enrolled. Patients in the YES1- high group exhibited significantly better OS and PFS, compared with those in the YES1-low group (P=0.02 and P=0.03, respectively). Further univariate and multivariate regression analyses indicated YES1 as an independent prognostic factor for the OS of patients with EOC. Notably, within the high YES1 expression group, 40 cases (74.1%) were of the platinum-sensitive group while 14 (25.9%) overlapped were of the platinum- resistant group. Conversely, in the low YES1 expression group, 11 cases (47.8%) were platinum-sensitive, and 12 (52.2%) platinum-resistant. Overall, patients within the high YES1 expression group were deemed significantly more sensitive to platinum-based chemotherapy than the low YES1 expression group (P=0.03), and YES1 levels were consistently and significantly higher in the platinum-sensitive group. Conclusions. High YES1 cytoplasmic expression in EOC patient tissue is significantly correlated with favorable prognosis. Patients with high YES1 expression tend to be sensitive to platinum-based chemotherapy.
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    Hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) - pathological evidence for a predominance of steatohepatitic inflammatory non-proliferative subtype
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Campos de, Priscila B.; Oliveira, Claudia P.; Stefano, José T.; Martins-Filho, Sebastião N.; Chagas, Aline L.; Herman, Paulo; Albuquerque de, Luiz C.; Alvares-da-Silva, Mário R.; Longatto-Filho, Adhemar; Carrilho, Flair J.; Alves, Venancio A.F.
    Objectives. This study evaluated clinical and pathological aspects of patients with hepatocellular carcinoma (HCC) secondary to non-alcoholic fatty liver disease (NAFLD) and related these factors to immunohistochemical markers representative of the proliferative class. Methods. We evaluated 35 HCC nodules from 21 patients diagnosed with NAFLD undergoing liver resection (n=12) or liver transplantation (n=8) or both (n=1). Demographic, clinical and biochemical data were compared to histological features and to immunohisto- chemical reactivity for K19 and Ki-67. Results. Cirrhosis was present in 58% of patients. Ages ranged from 50 to 77 years. Sixteen patients (76%) were male and had type 2 diabetes mellitus, 81% had arterial hypertension, and 90% had BMI above 25 kg/m 2. Alpha-fetoprotein levels were normal in 62% of patients. Twenty-five (70%) nodules were diagnosed as “steatohepatitic HCC”. Only 32% of the nodules presented high levels of Ki-67 (>10%) and/or K19 (>5%), although 63% were poorly differentiated (G.3/G.4) according to Edmondson & Steiner grading system. K19 positivity (>5%) was associated with higher degree of intratumoral inflammation (G.2/G.3), and with fibrosis, both at the center of the tumor and at the tumor front, whereas Ki-67 positivity (>10%) was associated with ballooning of neoplastic cells and occurred in more than 70% in non-cirrhotic patients. Conclusion. NAFLD-related HCC was found in non- cirrhotic patients in 42% of cases, alpha-fetoprotein level was normal in 63% and "steatohepatitic HCC" was the predominant histological type. Immunoexpression of K19 and/or Ki-67 occurred in 32% of the nodules and were associated with intratumoral inflammation and ballooning, suggesting that HCC in MtS may be preferentially “an inflammatory, non-proliferative subtype of HCC”
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    Therapeutic effects of platelet derived growth factor overexpressed-mesenchymal stromal cells and sheets in canine skin wound healing model
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Kim, Namyul; Choi, Kyeong Uk; Lee, Eunbee; Lee, Seoyun; Oh, Jiwon; Kim, Woo keyoung; Woo, Sang-Ho; Kim, Dae-Yong; Kim, Wan-Hee; Kweon, Oh-kyeong
    Adipose-derived mesenchymal stromal cells (Ad-MSCs) have excellent potential for skin wound repair. Moreover, platelet-derived growth factor (PDGF) has strong wound healing properties. The purpose of the present study was to compare the healing effects of PDGF-overexpressing canine allogeneic Ad-MSCs (PDGF-MSCs) and their cell sheets (PDGF-CSs) as compared to unexpressed Ad-MSCs (U-MSCs) and their cell sheets (UCSs) in a cutaneous wound healing model induced upon dogs. In in vitro study, the expression of immunomodulatory and growth factors was assessed by qRT-PCR. In in vivo study, cells and sheets were transplanted into a square-shaped full-thickness (1.5×1.5 cm) skin defect model created in 12 dogs. After 5 and 10 days, wounds were harvested and evaluated macroscopically and histopathologically. The qRT-PCR results showed that the PDGF-B gene was significantly upregulated (p<0.05) in PDGF-CS and PDGF-MSCs groups. Upon gross analysis of the wound, all stromal cells and their sheet groups showed accelerated (p<0.05) cutaneous wound healing compared to the negative control groups. As compared to U-MSCs and UCSs, the PDGF-MSCs showed significant epithelization on days 5 and 10 of healing, whereas PDGF-CSs showed improved epithelization only on day 10. In the granulation tissue analysis, PDGF-CSs and UCSs promoted more formation (p<0.05) of upper granulation tissue, collagen, and activated fibroblasts than PDGF- MSCs, and U-MSCs. Especially, the PDGF-CSs presented the highest formation and maturation of granulation tissue among all groups. All considered, PDGF overexpressed stromal cells or cells sheets can improve cutaneous wound healing in a canine model.
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    Next generation sequencing identifies novel potential actionable mutations for grade I meningioma treatment
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Pepe, Francesco; Pisapia, Pasquale; Del Basso de Caro, Maria Laura; Conticelli, Floriana; Malapelle, Umberto; Troncone, Giancarlo; Martinez, Juan Carlos
    Meningiomas are common brain tumors that arise from the meningeal membranes that envelope the brain and spinal cord. The World Health Organization classifies these tumors into three histopathological grades. Because of tumor recurrence, treating meningiomas may be challenging even in well- differentiated grade I (GI) neoplasms. Indeed, around 5% of completely resected GI meningiomas relapse within 5 years. Therefore, identifying driver mutations in GI meningiomas through next generation sequencing (NGS) assays is paramount. The aim of this study was to validate the use of the 50-gene AmpliSeq Hotspot Cancer Panel v2 to identify the mutational status of 23 GI meningioma, namely, 12 non recurrent and 11 recurrent. In 18 out of the 23 GI meningiomas analyzed, we identified at least one gene mutation (78.2%). The most frequently mutated genes were c-kit (39.1%), ATM (26.1%), TP53 (26.1%), EGFR (26.1%), STK11 (21.7%), NRAS (17.4%), SMAD4 (13%), FGFR3 (13%), and PTPN11 (13%); less frequent mutations were SMARCB1 (8.7%), FLT3 (8.7%), KRAS (8.7%), FBWX7 (8.7%), ABL1 (8.7%), ERBB2 (8.7%), IDH1 (8.7%), BRAF (8.7%), MET (8.7%), HRAS (4.3%), RB1 (4.3%), CTNNB1 (4.3%), PIK3CA (4.3%), VHL (4.3%), KDR (4.3%), APC (4.3%), NOTCH1 (4.3%), JAK3 (4.3%), and SRC (4.3%). To our knowledge, mutations in all of these genes, except for TP53, STK11, SMARCB1, PIK3CA, VHL, and BRAF, have never been described before in meningiomas. Hence, these findings demonstrate the viability of NGS to detect new genetic alterations in GI meningiomas. Equally important, this technology enabled us to detect possible novel actionable mutations not previously associated with GI and for which selective inhibitors already exist
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    Effects of estrogen on STIM1/Orai1 in the sublingual gland of ovariectomized rats
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Bai, Yun; Li, Bing; Wang, Sinan; Jiang, Hai; Li, Junlei; Wang, Wenjuan; Wang, Ke; Qin, Lihua; Jia, Jing
    Background. Studies have shown that estrogen can protect the function of the sublingual gland, but the specific mechanism is still unclear. Besides, the STIM1/Orai1 pathway is important to secretion in the salivary gland. Here, we explore the possible effects of estrogen on sublingual gland function by observing changes of STIM1 and Orai1 levels in the sublingual glands of ovariectomized rats. Methods. 42 adult female Sprague-Dawley rats were randomly divided into three groups: SHAM, OVX, and OVX+E (n=14 per group). Two weeks after ovariectomy, rats were treated with estrogen (β-estradiol). The expression of STIM1 and Orai1 in the sublingual gland were observed by double label-immunohistochemistry and immunofluorescence. Calcium imaging was conducted to observe changes in cellular Ca 2+ levels. Results. IHC and IF showed that the levels of both STIM1 and Orai1 decreased following ovariectomy, but increased to SHAM levels after estrogen treatment. By IF, STIM1 and Orai1 exhibited perfect co-localization. Calcium imaging results showed that the Ca 2+ in the cells decreased after ovariectomy. Estrogen intervention returned levels of these proteins and Ca 2+ to the same as those in the control group. Conclusion. This study demonstrates that low estrogen status significantly reduced the expression of STIM1 and Orai1 in the sublingual gland of rats, along with cellular Ca 2+ levels. These data provide insight into the likely mechanisms underlying sublingual gland secretion dysfunction during menopause