Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous endometrium

2006 ◽  
Vol 16 (3) ◽  
pp. 1412-1418 ◽  
Author(s):  
S. Erkanli ◽  
F. Kayaselcuk ◽  
E. Kuscu ◽  
T. Bagis ◽  
F. Bolat ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Endometrial Hyperplasia ◽  
Survivin Expression ◽  
Myometrial Invasion ◽  
Immunohistochemical Analysis ◽  
Endometrioid Adenocarcinoma ◽  
Tissue Samples ◽  
Proliferative Endometrium ◽  
Endometrial Carcinomas ◽  
First Time

We aimed to investigate if expressions of survivin and p27 proteins are involved in the development of endometrioid carcinoma, along with whether there are any correlations between these proteins and loss of wild-type PTEN that is found in up to 80% of endometrial carcinomas. We also studied their correlations with classical prognostic factors and survival in endometrial carcinoma. To our knowledge, this is the first time survivin expression is investigated in endometrial hyperplasia along with endometrioid adenocarcinoma. For immunohistochemical analysis, 29 endometrioid adenocarcinoma, 38 endometrial hyperplasia, and 10 proliferative endometrium tissue samples were selected in the pathology archives. Staining of cells was scored as +2 if >50%, +1 if <50%, and negative if none were stained positive. Survivin expression increased from proliferative to hyperplasia to carcinoma cases. PTEN and p27 expressions decreased in hyperplasia and carcinoma cases with respect to proliferative endometrium. All these differences were statistically significant (P < 0.05). PTEN positively correlated to p27 (P < 0.05); however, neither was correlated with survivin. None of these genes were correlated with classical prognostic factors such as grade and myometrial invasion in endometrioid adenocarcinoma. However, mean survival was statistically significantly higher in PTEN-positive cases (46.6 vs 16.4 months) (P < 0.05). Survivin overexpression might be one of the important mechanisms in the development of endometrioid adenocarcinoma along with lost or decreased activity of PTEN and p27. However, survivin seems to exert its role in ways different from those of PTEN or p27 in the development of endometrioid adenocarcinoma. These findings on the role of survivin in endometrioid adenocarcinoma should be confirmed and the pathways through which survivin acts in endometrioid adenocarcinoma studied further with a larger sample size.

scholarly journals INNV-03. A MICROFLUIDIC CULTURE PARADIGM FOR THE EX VIVO MAINTENANCE OF HUMAN GLIOBLASTOMA TISSUE - A NEW GBM MODEL?

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi130-vi131
Author(s):  
Farouk Olubajo ◽  
Shailendra Achawal ◽  
Chittoor Rajaraman ◽  
Gerry O’Reilly ◽  
John Greenman
Keyword(s):  
Ex Vivo ◽  
Annexin V ◽  
Immunohistochemical Analysis ◽  
Fresh Tissue ◽  
Tissue Samples ◽  
Tissue Sections ◽  
Human Gbm ◽  
On Chip ◽  
First Time ◽  
Improve Patient

Abstract The genetic and molecular variations that exist within Glioblastoma (GBM) determine treatment responses. One way to improve patient outcomes is to optimise treatment(s) pre-clinically by studying each tumour on an individual basis. Presented here are the results of a pilot study on the maintenance of human GBM tissue on a microfluidic platform. The device, fabricated using a photolithographic process, was composed of two layers of glass bonded together to contain a tissue chamber and a network of microchannels. A thin mesh layer was inserted to separate the tissue chamber from the microchannels and prevented blockage of the chip. Over an 18-month period, 33 patients were recruited, and 128 tissue sections were maintained in microfluidic devices for an average of 72 hours (h). Tissue viability as measured by Annexin V and Propidium Iodide staining showed that viability was 61.1 % in tissue maintained on chip after 72 h, compared with 68.9 % for fresh tissue analysed at the commencement of the experiment (P < 0.05). Other biomarkers, including Lactate Dehydrogenase (LDH) release and Trypan Blue assay, supported the viability of the tissue maintained on chip. Histological appearances of the tissue remained unchanged during the maintenance period and immunohistochemical analysis of Ki67 and Caspase 3 also showed no statistically significant differences. Analysis has shown a trend with tumours associated with poorer prognoses (e.g. recurrent tumours and IDH wildtype) displaying higher viability on chip compared to tumours linked with better outcomes (Grade 1–3 gliomas, IDH mutants and primary tumours). This work has demonstrated for the first time that human GBM tissue can be maintained ex vivo within a microfluidic device with viability comparable to fresh tissue samples. The model has the potential to be developed as a new platform for studying the biology of brain tumours, with the aim of facilitating personalised treatments.

scholarly journals Histopathological spectrum of endometrium in abnormal uterine bleeding

2018 ◽  
Vol 7 (9) ◽  
pp. 3633 ◽  
Author(s):  
Simridhi Bindroo ◽  
Monika Garg ◽  
Tajinder Kaur
Keyword(s):  
Endometrial Hyperplasia ◽  
Histopathological Examination ◽  
Age Groups ◽  
Healthy Woman ◽  
Abnormal Uterine Bleeding ◽  
Uterine Bleeding ◽  
Age Group ◽  
Proliferative Endometrium ◽  
Histopathological Workup ◽  
Endometrial Carcinomas

Background: Abnormal uterine bleeding (AUB) interferes with the quality of life of an otherwise healthy woman. Until the pathology underlying menorrhagia is, accurately diagnosed, proper therapy is hardly possible. The objective of the study was to analyze different histopathological patterns of endometrium in AUB and observe the incidence of various pathologies in different age groups and their relation to parity.Methods: This two-year prospective studywas done in the department of pathology in atertiary care centre, which included 250 cases of clinically diagnosed AUB patients were evaluated. Histopathological examination of endometrial biopsies and hysterectomy specimens were done, followed by clinical correlation.Results: Out of 250 cases of AUB, Premenopausal bleeding was seen in 216 cases (86.4%) and 34 cases (13.6%) had postmenopausal bleeding. The commonest finding observed in the study was proliferative phase endometrium (37.2%), followed by secretory endometrium (34%) and endometrial hyperplasia (16%). Disordered proliferative endometrium was seen in 2.4% of patients. Endometrial carcinoma was seen in 4 (1.6%) cases. Endometrial hyperplasia was seen mostly in the age group 41-50 years (27 cases). Two cases of endometrial carcinomas were presented after age 60 years.Conclusions: Our study revealed the highest incidence of AUB in the perimenopausal age group (41-50 years). Hence a thorough histopathological workup and clinical correlation are mandatory in cases of abnormal uterine bleeding.

Molecular iodine synergized and sensitized neuroblastoma cells to the antineoplastic effect of ATRA

2020 ◽  
Vol 27 (12) ◽  
pp. 699-710
Author(s):  
Irasema Mendieta ◽  
Gabriel Rodríguez-Gómez ◽  
Bertha Rueda-Zarazúa ◽  
Julia Rodríguez-Castelán ◽  
Winniberg Álvarez-León ◽  
...  
Keyword(s):  
Residual Disease ◽  
Neuroblastoma Cells ◽  
Survivin Expression ◽  
Body Weight Loss ◽  
Immunohistochemical Analysis ◽  
Molecular Iodine ◽  
Tyrosine Kinase Receptor ◽  
Adjuvant Effect

Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) is used as a treatment to decrease minimal residual disease. Molecular iodine (I2) induces differentiation and/or apoptosis in several neoplastic cells through activation of PPARγ nuclear receptors. Here, we analyzed whether the coadministration of I2 and ATRA increases the efficacy of NB treatment. ATRA-sensitive (SH-SY5Y), partially-sensitive (SK-N-BE(2)), and non-sensitive (SK-N-AS) NB cells were used to analyze the effect of I2 and ATRA in vitro and in xenografts (Foxn1 nu/nu mice), exploring actions on cellular viability, differentiation, and molecular responses. In the SH-SY5Y cells, 200 μM I2 caused a 100-fold (0.01 µM) reduction in the antiproliferative dose of ATRA and promoted neurite extension and neural marker expression (tyrosine hydroxylase (TH) and tyrosine kinase receptor alpha (Trk-A)). In SK-N-AS, the I2 supplement sensitized these cells to 0.1 μM ATRA, increasing the ATRA-receptor (RARα) and PPARγ expression, and decreasing the Survivin expression. The I2 supplement increased the mitochondrial membrane potential in SK-N-AS suggesting the participation of mitochondrial-mediated mechanisms involved in the sensibilization to ATRA. In vivo, oral I2 supplementation (0.025%) synergized the antitumor effect of ATRA (1.5 mg/kg BW) and prevented side effects (body weight loss and diarrhea episodes). The immunohistochemical analysis showed that I2 supplementation decreased the intratumoral vasculature (CD34). We suggest that the I2 + ATRA combination should be studied in preclinical and clinical trials to evaluate its potential adjuvant effect in addition to conventional treatments.

Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients

2001 ◽  
Vol 11 (4) ◽  
pp. 272-276 ◽  
Author(s):  
N. Nishimura ◽  
T. Hachisuga ◽  
T. Saito ◽  
T. Kawarabayashi
Keyword(s):  
Breast Cancer ◽  
Endometrial Carcinoma ◽  
Cancer Patients ◽  
Myometrial Invasion ◽  
Tamoxifen Treatment ◽  
Adjuvant Tamoxifen ◽  
Serous Carcinoma ◽  
Breast Cancer Patients ◽  
Two Stage ◽  
Endometrial Carcinomas

Abstract.Nishimura N, Hachisuga T, Saito T, Kawarabayashi T. Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients.This study aimed to detail the clinicopathologic features of endometrial carcinomas that developed in Japanese patients receiving adjuvant tamoxifen treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen-treated breast cancer patients were collected from two medical centers. The endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The tumor was limited to the endometrium in two cases. Myometrial invasion was limited to the inner half of the myometrium in five cases and involved the outer half in three. A mild degree of lymphovascular space invasion was identified in five cases. Deep cervical invasion was recognized in one case. The cell types comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of eight postmenopausal endometrial carcinomas were associated with polypoid endometrial lesions composed of cystically dilated atrophic and proliferative glands widely separated by fibrotic stroma. Two patients with retroperitoneal lymph node metastases died of endometrial cancer. One patient developed a contralateral breast cancer during tamoxifen treatment. No patient died of breast cancer. We did not demonstrate a higher frequency of either high-grade tumors or unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer patients.

scholarly journals Contrast-Enhanced Ultrasound Imaging of Uterine Disorders: A Systematic Review

2021 ◽  
pp. 016173462110174
Author(s):  
Barbara Stoelinga ◽  
Lynda Juffermans ◽  
Anniek Dooper ◽  
Marleen de Lange ◽  
Wouter Hehenkamp ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Myometrial Invasion ◽  
Diagnostic Technique ◽  
Specific Information ◽  
Full Potential ◽  
Contrast Enhanced Ultrasound ◽  
Literature Overview ◽  
Benign Tissue ◽  
Contrast Enhanced ◽  
Endometrial Carcinomas

Uterine disorders are often presented with overlapping symptoms. The microvasculature holds specific information important for diagnosing uterine disorders. Conventional sonography is an established diagnostic technique in gynecology, but is limited by its inability to image the microvasculature. Contrast-enhanced ultrasound (CEUS), is capable of imaging the microvasculature by means of intravascular contrast agents; that is, gas-filled microbubbles. We provide a literature overview on the use of CEUS in diagnosing myometrial and endometrial disorders, that is, fibroids, adenomyosis, leiomyosarcomas and endometrial carcinomas, as well as for monitoring and enhancing the effectiveness of minimally invasive therapies. A systematic literature search with quality assessment was performed until December 2020. In total 34 studies were included, published between 2007 and 2020.The results entail a description of contrast-enhancement patterns obtained from healthy tissue and from malignant and benign tissue; providing a first base for potential diagnostic differentiation in gynecology. In addition it is also possible to determine the degree of myometrial invasion in case of endometrial carcinoma using CEUS. The effectiveness of minimally invasive therapies for uterine disorders can safely and accurately be assessed with CEUS. In conclusion, the abovementioned applications of CEUS are promising and it is worth further exploring its full potential for gynecology by designing innovative and methodologically high-quality clinical studies.

An immunohistochemical study of estrogen and progesterone receptors in adenocarcinoma of the endometrium and in the adjacent mucosa

1995 ◽  
Vol 5 (4) ◽  
pp. 275-281 ◽  
Author(s):  
H. Kerner ◽  
E. Sabo ◽  
M. Friedman ◽  
D. Beck ◽  
O. Samare ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Endometrial Cancer ◽  
Progesterone Receptor ◽  
Estrogen Receptor Status ◽  
Endometrial Adenocarcinoma ◽  
Progesterone Receptors ◽  
Myometrial Invasion ◽  
Inverse Correlation ◽  
Immunohistochemical Analysis ◽  
Receptor Status

The immunoperoxidase stain for estrogen and progesterone receptor content in endometrial adenocarcinoma was correlated with the grade and stage, level of myometrial invasion, age and survival of the patients. Anti-estrogen and anti-progesteone receptor monoclonal antibodies were applied to paraffin-embedded tissue from hysterectomy specimens of 100 patients with adenocarcinoma of the endometrium. In 34 of the cases the receptors were studied in the endometrium adjacent to the tumor and compared to the nuclear receptor content in the carcinoma. There was a high inverse correlation between the estrogen receptor status and the grade of tumor (R= − 0.45,P= 0.006). The estrogen receptor measured in the endometrium near the tumor showed a negative correlation with the grade of the tumor (R= −0.42,P= 0.013). The estrogen, but not the progesterone, receptor content, was positively related to the age of the patient (P< 0.05). No significant correlation of the receptor status with the depth of myometrial invasion was found, despite the obvious interdependence between the grade and myometrial invasion. The progesterone receptor staining index appeared to be a distinct independent prognostic factor in endometrial cancer. The immunohistochemical analysis of the steroid hormone status in endometrial cancer therefore offers an alternative to the quantitative ligand-binding assay.

Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

1993 ◽  
Vol 3 (6) ◽  
pp. 363-368 ◽  
Author(s):  
T. Hachisuga ◽  
K. Fukuda ◽  
M. Uchiyama ◽  
N. Matsuo ◽  
T. Iwasaka ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Proliferative Activity ◽  
P53 Protein ◽  
Myometrial Invasion ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Normal Endometrium ◽  
P53 Expression ◽  
Dna Polymerase Α ◽  
Endometrial Carcinomas

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.

Abstract P195: No Functional Nerve Recovery To 6 Months Post Renal Denervation With Rf Energy In A Normotensive Pig Model

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Andrew Sharp ◽  
Stefan Tunev ◽  
Markus P Schlaich ◽  
David P LEE ◽  
Aloke Finn ◽  
...  
Keyword(s):  
Animal Studies ◽  
Renal Denervation ◽  
Blood Pressure Reduction ◽  
Immunohistochemical Analysis ◽  
Swine Model ◽  
Renal Nerve ◽  
Tissue Samples ◽  
Axon Density ◽  
Rf Energy

Background: The safety and efficacy of catheter-based radio frequency (RF) renal denervation (RDN) have been demonstrated in randomized, sham-controlled trials. Long-term durability of blood pressure reduction following RDN has also been demonstrated by all-comer registries, although published pre-clinical reports of functional renal nerve regrowth are not consistent. We quantified the processes that support RDN procedural durability utilizing animal models. Methods: Animal studies were conducted in accordance with published guidelines. RDN was performed (4 lesions in the main renal artery) in normotensive swine using the Symplicity Spyral™ RDN system (Medtronic, Santa Rosa, CA, USA). Two additional groups not undergoing RDN served as control. Serial histological tissue samples were obtained in separate groups at 7 (n=12/group) and 180 (N=16/group) days post-procedure in all animals followed by bioanalytical quantification of cortical norepinephrine (NE) levels and immunohistochemical analysis of renal cortical axon density in matched samples. Results: Renal cortical axon density and NE levels were significantly reduced at 7 days and persisted through 180 days following RDN compared with control ( Figure ). Nerve fibrosis and necrosis were observed in the region of ablation, while nerve body atrophy was apparent distal to ablation location at 180 days. Conclusions: Reductions in both NE and renal cortical axon density were sustained at 7 and 180 days post-RDN procedure using RF renal denervation in a normotensive swine model. These data confirm and extend other pre-clinical and clinical evidence of long-term durability of the RDN procedure using RF energy.

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