Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous leiomyomatosis (IVL) is a rare neoplasm that is characterized by smooth muscle cell proliferation within venous vessels. The aim of this study is to investigate the clinicopathological features, immunophenotypes, and MED12 gene mutations in IVL. Nine cases of IVL from the Affiliated Hospital of Qingdao University were collected, and the clinicopathological features were reviewed. The immunohistochemical expressions of p16, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alpha thalassemia/mental retardation syndrome X-linked (ATRX), retinoblastoma 1 (RB1), fumarate hydratase (FH), and p53, were evaluated. The mutation status of MED12 gene exon 2 was detected by Sanger sequencing. All the 9 patients were women ranging from 32 to 58 years, and uterine leiomyomas were identified in 5 patients. Immunohistochemical staining showed that all IVL and leiomyoma samples were positive for estrogen receptor and progesterone receptor, but negative for CD34. IVL displayed similar immunostaining patterns with their uterine counterparts with focal p16 immunostaining. FH, PTEN, ATRX, and RB1 were variably positive, and p53 and Ki-67 positive rates were less than 5% in all cases. Two novel genetic variations at MED12 exon 2, a synonymous mutation c.141C>T (p.Asn47=), and an in-frame deletion mutation c.133_147del15 (p.Phe45_Pro49del) were identified in two IVL cases. One missense mutation c.131G>A (p.Gly44Asp) was identified in one uterine leiomyoma. The remaining 11 tumor samples (7 IVL cases and 4 uterine leiomyomas) showed no mutations at MED12 exon 2. Our results showed two novel MED12 mutations in IVL. The MED12 mutations are different between IVL and uterine leiomyoma. These findings indicate that IVL is a unique entity and different from uterine leiomyoma.
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PMID:MED12 exon 2 mutation is uncommon in intravenous leiomyomatosis: clinicopathologic features and molecular study. 3224 Jun 66

Although uterine leiomyomas are the most common benign uterine tumors in women, there is no effective therapy that can also preserve the uterus and maintain fertility. The work aimed to work was to discover a potential natural agent that has pharmacological activities on uterine leiomyomas with fewer adverse effects. We chose Rhus verniciflua Stokes (RVS) as a candidate after primary cytotoxicity testing, and analyzed the RVS components that showed pharmacological activity. Leiomyoma cells and myometrium cells were cultured from uterine tissues obtained from patients, and were treated with RVS at varying concentrations. RVS was cytotoxic in both leiomyoma and myometrium cells; however, the effects were more prominent in the leiomyoma cells. Among the bioactive components of RVS, fisetin showed significant pharmacological effects on leiomyoma cells. Fisetin showed excellent leiomyoma cell cytotoxicity and induced apoptotic cell death with cell cycle arrest. The apoptotic cell death appeared to involve not one specific pathway but multichannel pathways (intrinsic, extrinsic, MARK, and p53-mediated pathways), and autophagy. The multichannel apoptosis pathways were activated with a low concentration of fisetin (<IC20) and were more vigorously activated at high concentrations (>IC50). This is the first demonstration to show the pharmacological activities of fisetin on leiomyoma cells. These findings suggest that fisetin may be used for the prevention and treatment of uterine leiomyomas. Since fisetin can be obtained from plants, it may be a safe and effective alternative treatment for uterine leiomyomas.
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PMID:Fisetin induces apoptosis in uterine leiomyomas through multiple pathways. 3240 92

Our objective was to evaluate the diagnostic utility of 2 new proliferation markers, cyclin D1 and minichromosome maintenance complex component 2 (MCM2), in comparison with p16, p53, and Ki67 in differentiating the spectrum of smooth muscle tumors. An institutional database search from 2009 to 2017 identified 10 cases of uterine leiomyoma with bizarre nuclei (LBN), 12 smooth muscle tumors of uncertain malignant potential, and 13 leiomyosarcomas (LMS). Ten resected leiomyomas (LM) were included as controls. Immunohistochemistry was performed on the befitting representative block from each case. Ki67 was <10% in all LMs and LBNs, whereas >10% in all LMSs. Although wild-type in majority of cases, p53 was overexpressed in 38% of LMSs. Cyclin D1 nuclear positivity in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials ranged from 0% to 65% of neoplastic cells with mostly weak to moderate staining intensity. Instead, cyclin D1 expression was <5% in all LMSs. The ratio of MCM2 positivity exhibited a similar wide range (<1%-80%) in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials but interestingly, 92% (12/13) of LMSs were diffusely and strongly positive for MCM2 (>80% cell positivity). Overall, for diagnosis of LMS, the sensitivity for diffuse intense MCM2 staining was higher (92%) compared with diffuse staining for p16 (77%); however, specificity of MCM2 and p16 was comparable (94% and 97%, respectively). Herein, we describe the immunohistochemical profile of 2 new proliferation markers, cyclin D1 and MCM2 in uterine smooth muscle tumors. A combination of diffuse strong MCM2 and p16 reactivity with increased Ki67 index can reliably distinguish LMSs from benign histologic mimics.
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PMID:Combination of MCM2 With Ki67 and p16 Immunohistochemistry Can Distinguish Uterine Leiomyosarcomas. 3251 21


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