27 research outputs found
Trends in the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer, 1990–2010
Expression of mitochondrial transcription factor A in endometrial carcinomas: clinicopathologic correlations and prognostic significance
Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA. This study was conducted to elucidate the clinicopathologic and prognostic significance of mtTFA in patients with endometrial carcinoma. This study investigated the relationship between the immunohistochemical expression of mtTFA and various clinicopathological variables in 276 endometrial carcinomas, including 245 endometrioid adenocarcinomas and 31 nonendometrioid carcinomas (21 serous carcinomas and 10 clear cell adenocarcinomas). Both uni- and multivariate regression analyses were performed. The mtTFA labeling index of endometrioid adenocarcinomas ranged from 0% to 98%, with a median value of 32%, which was selected as the cut-off point for mtTFA expression. The mtTFA expression in endometrioid adenocarcinomas was significantly associated with the surgical stage, myometrial invasion, lymphovascular space invasion, cervical invasion, and lymph node metastasis. In contrast, no correlation between clinicopathologic variables and mtTFA expression was found in nonendometrioid carcinomas. Correlation analysis between mtTFA and p53 expression by using the Pearson test showed significant correlation in endometrioid adenocarcinomas (P = 0.007), but no significant correlation in nonendometrioid carcinomas (P = 0.947). A univariate survival analysis showed that the 10-year overall survival rate of the patients with mtTFA-positive endometrioid adenocarcinoma was significantly worse than that of patients with mtTFA-negative endometrioid adenocarcinoma (80.8% vs. 93.8%, P = 0.012). However, the multivariate analysis revealed that mtTFA expression in endometrioid adenocarcinomas was no independent prognostic factor. The positive mtTFA expression is a useful maker for progression of the tumors and the poor prognosis of the patients in endometrioid adenocarcinomas
Expression of p53 in endometrial polyps with special reference to the p53 signature
We herein examined the significance of the
p53 expression in endometrial polyps (EMPs). A total of
133 EMPs, including 62 premenopausal and 71
postmenopausal women with EMP, were immunohistochemically studied for the expression of estrogen
receptor (ER)-alpha, Ki-67 and p53. Apoptotic cells
were identified using a TUNEL assay. A DNA sequence
analysis of TP53 exons 5 to 9 was performed. Among
the premenopausal EMPs, a multivariate analysis
showed the labeling index (LI) for Ki-67 to correlate
significantly with that for p53 (P<0.001), but not that for
apoptosis. On the contrary, among the postmenopausal
EMPs, the LI for Ki-67 correlated significantly with that
for apoptosis (P<0.001). The p53 signature (p53S) was
defined by endometrial epithelial cells, which are
morphologically benign in appearance but display 12 or
more consecutive epithelial cell nuclei with strong p53
immunostaining. The p53S was found in nine (12.7%)
postmenopausal EMPs (mean age: 70.2 years). The
median Ki-67 index for the p53S was 7%, with no
significant difference from that of the glands of the
postmenopausal EMPs without the p53S (P=0.058). The
median apoptotic index for the p53S was 0%, which was
significantly lower than that of the postmenopausal
EMPs without the p53S (P=0.002). Two of four p53Ss
showed TP53 mutations according to the DNA sequence
analysis. The presence of the p53S is not rare in
postmenopausal EMPs with an advanced age. Among
postmenopausal EMPs, the LI of Ki-67 significantly
correlates with that of apoptosis. However, such a
positive correlation between the LI of Ki-67 and
apoptosis is not observed in p53S
Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers : A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent
For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers
PACAP suppresses dry eye signs by stimulating tear secretion
Dry eye syndrome is caused by a reduction in the volume or quality of tears. Here, we show that pituitary adenylate cyclase-activating polypeptide (PACAP)-null mice develop dry eye-like symptoms such as corneal keratinization and tear reduction. PACAP immunoreactivity is co-localized with a neuronal marker, and PACAP receptor (PAC1-R) immunoreactivity is observed in mouse infraorbital lacrimal gland acinar cells. PACAP eye drops stimulate tear secretion and increase cAMP and phosphorylated (p)-protein kinase A levels in the infraorbital lacrimal glands that could be inhibited by pre-treatment with a PAC1-R antagonist or an adenylate cyclase inhibitor. Moreover, these eye drops suppress corneal keratinization in PACAP-null mice. PACAP eye drops increase aquaporin 5 (AQP5) levels in the membrane and pAQP5 levels in the infraorbital lacrimal glands. AQP5 siRNA treatment of the infraorbital lacrimal gland attenuates PACAP-induced tear secretion. Based on these results, PACAP might be clinically useful to treat dry eye disorder
Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver–Russell Syndrome-compatible phenotype
Molecular and Clinical Studies in 138 Japanese Patients with Silver-Russell Syndrome
<div><p>Background</p><p>Recent studies have revealed relative frequency and characteristic phenotype of two major causative factors for Silver-Russell syndrome (SRS), i.e. epimutation of the <i>H19</i>-differentially methylated region (DMR) and uniparental maternal disomy 7 (upd(7)mat), as well as multilocus methylation abnormalities and positive correlation between methylation index and body and placental sizes in <i>H19</i>-DMR epimutation. Furthermore, rare genomic alterations have been found in a few of patients with idiopathic SRS. Here, we performed molecular and clinical findings in 138 Japanese SRS patients, and examined these matters.</p> <p>Methodology/Principal Findings</p><p>We identified <i>H19</i>-DMR epimutation in cases 1–43 (group 1), upd(7)mat in cases 44–52 (group 2), and neither <i>H19</i>-DMR epimutation nor upd(7)mat in cases 53–138 (group 3). Multilocus analysis revealed hyper- or hypomethylated DMRs in 2.4% of examined DMRs in group 1; in particular, an extremely hypomethylated <i>ARHI</i>-DMR was identified in case 13. Oligonucleotide array comparative genomic hybridization identified a ∼3.86 Mb deletion at chromosome 17q24 in case 73. Epigenotype-phenotype analysis revealed that group 1 had more reduced birth length and weight, more preserved birth occipitofrontal circumference (OFC), more frequent body asymmetry and brachydactyly, and less frequent speech delay than group 2. The degree of placental hypoplasia was similar between the two groups. In group 1, the methylation index for the <i>H19</i>-DMR was positively correlated with birth length and weight, present height and weight, and placental weight, but with neither birth nor present OFC.</p> <p>Conclusions/Significance</p><p>The results are grossly consistent with the previously reported data, although the frequency of epimutations is lower in the Japanese SRS patients than in the Western European SRS patients. Furthermore, the results provide useful information regarding placental hypoplasia in SRS, clinical phenotypes of the hypomethylated <i>ARHI</i>-DMR, and underlying causative factors for idiopathic SRS.</p> </div