Expression of anti‑apoptotic protein survivin in human endometrial carcinoma: Clinical and pathological associations as a separate factor and in combination with concomitant PTEN and p53 expression

Pyrrolidinedithiocarbamate (PDTC) is a potent antioxidant and an inhibitor of nuclear factor-κB (NF-κB). The present study examined the impact of PDTC preconditioning on gastric protection in response to ischemia-reperfusion (I/R) injury to the rat stomach. Male Wistar rats were recruited and divided into 3 groups (n=7). One group was subjected to gastric ischemia for 30 min and reperfusion for 1 hour. The second group of rats was preconditioned with PDTC (200 mg/kg body mass i.v.) 15 min prior to ischemia and before reperfusion. The third group of rats was sham-operated and served as the control group. Gastric I/R injury increased serum lactate dehydrogenase level, vascular permeability of gastric mucosa (as indicated by Evans blue dye extravasation) and gastric content of inflammatory cytokine; tumor necrosis factor-α (TNF-α). Moreover, oxidative stress was increased as indicated by elevated lipid peroxides formation (measured as thiobarbituric acid reactive substances) and depleted reduced glutathione in gastric tissues. NF-κB translocation was also detected by electrophoretic mobility shift assay. Microscopically, gastric tissues subjected to I/R injury showed ulceration, hemorrhages, and neutrophil infiltration. Immunohistochemical studies of gastric sections revealed increased expression of p53 and Bcl-2 proteins. PDTC pretreatment reduced Evans blue extravasation, serum lactate dehydrogenase levels, gastric TNF-α levels, and thiobarbituric acid reactive substances content, and increased gastric glutathione content. Moreover, PDTC pretreatment abolished p53 expression and inhibited NF-κB translocation. Finally, histopathological changes were nearly restored by PDTC pretreatment. These results clearly demonstrate that NF-κB activation and pro-apoptotic protein p53 induction are involved in gastric I/R injury. PDTC protects against gastric I/R injury by an antioxidant, NF-κB inhibition, and by reduction of pro-apoptotic protein p53 expression, which seems to be downstream to NF-κB, thus promoting cell survival. Key words: pyrrolidinedithiocarbamate, ischemiareperfusion injury, gastric mucosa, nuclear factor-κB, inflammatory cytokines, oxidative stress.

Download Full-text

Significantly decreased P27 expression in endometrial carcinoma compared to complex hyperplasia with atypia (correlation with p53 expression)

Pathology & Oncology Research ◽

10.1007/bf02893462 ◽

2004 ◽

Vol 10 (2) ◽

pp. 89-97 ◽

Cited By ~ 11

Author(s):

Sevgiye Kacar Özkara ◽

Aydin Corakci

Keyword(s):

Endometrial Carcinoma ◽

P53 Expression

Download Full-text

Immunocytochemical indicators of apoptosis in gingival tissues of patients with chronic periodontitis

Journal of Medical Science ◽

10.20883/medical.e42 ◽

2014 ◽

Vol 83 (1) ◽

pp. 37-46

Author(s):

Aldona Kasprzak ◽

Miłosz Hausmann ◽

Agata Małkowska-Lanzafame ◽

Joanna Surdyk-Zasada ◽

Wiesława Przybyszewska ◽

...

Keyword(s):

Chronic Periodontitis ◽

Caspase 3 ◽

Tissue Expression ◽

P53 Expression ◽

Effector Phase ◽

Apoptotic Protein ◽

Gingival Cells ◽

Apoptotic Proteins ◽

Inflammatory Infiltrates ◽

And Control

Introduction. Inflammatory mechanisms of chronic periodontitis (CP) may be linked to various forms of disturbances in apoptosis.Aim. The study aimed at comparison of tissue expression of anti-apoptotic protein (Bcl-2) and proapoptotic proteins (p53, caspase-3) in gingival tissues of 30 patients with CP and of 15 with healthy periodontium.Material and methods. Gingival samples (n = 68) were obtained during the open curettage procedure with gingivectomy of adult patients (18 women and 12 men) with CP. Classical immunocytochemical (IHC) method was used to detect apoptotic proteins, and the obtained expression was evaluated using semi-quantitative IRS scale.Results. No differences could be revealed in expression intensity or reciprocal correlations between apoptotic proteins within the group of patients with CP. Greater expression of the two apoptotic proteins (Bcl-2 and p53) were detected in patients with CP than in control individuals. Moreover, a more pronounced expression of Bcl-2 was demonstrated in gingival samples of patients with localised form as compared to generalised form of CP. Expression of caspase-3 (effector phase of apoptosis) manifested no differences between CP and control individuals. Greater expression of the anti-apoptotic protein Bcl-2 and caspase-3 was detected in cells of inflammatory infiltrates in lamina propria than in keratinocytes.Conclusions. In CP significant alterations developed in expression of indicators of apoptosis, with prevalence of Bcl-2 and p53 expression, as compared to the control. The localised form of CP was linked to higher proportion of Bcl-2-positive cells of inflammatory infiltrates, suggesting that apoptosis was inhibited mainly in this form of CP. The comparable expression of caspase-3 in gingival cells with CP and in control and absence of correlation with clinical data suggested that the process of apoptosis did not play a significant role in destruction of periodontium tissues in CP.

Download Full-text

Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200201000-00018 ◽

2002 ◽

Vol 12 (1) ◽

pp. 110-118 ◽

Cited By ~ 9

Author(s):

C Lundgren ◽

G Auer ◽

B Frankendal ◽

B Moberger ◽

B Nilsson ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Proliferative Activity ◽

Nuclear Dna ◽

Dna Ploidy ◽

Nuclear Dna Content ◽

Image Cytometry ◽

P53 Expression ◽

Degree Of Differentiation ◽

Histopathologic Features ◽

Mib 1

Abstract.Lundgren C, Auer G, Frankendal B, Moberger B, Nilsson B, Nordström B. Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.The purpose of this study was to evaluate the prognostic impact of image cytometry DNA ploidy, MIB-1, and p53 in relation to clinicopathologic variables in 376 consecutive patients with endometrial carcinoma stages I–IV. Following primary treatment 358 patients were considered tumor-free. Relapses and tumor-specific deaths of these patients were noted. Image cytometry DNA ploidy (n = 340) and expression of MIB-1 (n = 318) and p53 (n = 323) were studied. In univariate analysis, stage (P < 0.001), histopathologic subtype (P < 0.001), degree of differentiation (P < 0.001), HRT (P = 0.034), DNA ploidy (P < 0.001), and p53 (P < 0.001) were significant predictors of relapse. Patient age showed that the estimated mean risk of relapse increases with nearly 64% per decade in life (P 0.003), and the MIB-1 expression with 21% per 10-unit increment (P 0.004). In multivariate analysis, degree of differentiation, MIB-1, and p53 lost their prognostic capability. However, after stage and histopathologic subtype, image cytometry DNA ploidy was the strongest predictor of outcome and was of value in predicting the risk for relapse. The combination of DNA ploidy, MIB-1, and p53 expression was an even stronger predictor of relapse-free survival than the individual prognostic factors.

Download Full-text

Molecular-based classification algorithm for endometrial carcinoma to categorize ovarian endometrioid carcinoma into prognostically significant groups.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17081 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17081-e17081

Author(s):

Carlos Parra-Herran ◽

Jordan Lerner-Ellis ◽

Bin Xu ◽

Dina Bassiouny ◽

Matthew Cesari ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Mutational Analysis ◽

Survival Rates ◽

The Cancer Genome Atlas ◽

Molecular Profile ◽

Endometrioid Carcinoma ◽

Wild Type ◽

Molecular Subgroup ◽

P53 Expression ◽

Excellent Outcome

e17081 Background: The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR) and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma (OEC), their role in predicting its molecular profile and prognosis is still not fully explored. Methods: OECs resected in a 14 year period were retrieved. Only tumors with confirmed endometrioid histology and negative WT1 were included. POLE mutational analysis and immunohistochemistry for p53, MLH1, MSH2, MSH6 and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. Following the molecular classifier proposed for endometrial carcinoma ( B J Cancer 2015;113:299-310), cases were classified as: POLE mutated, MMR abnormal, p53 abnormal and p53 wild type. Clinicopathologic information was recorded including patient outcome. Results: 73 tumors were successfully reviewed and tested. Of these, 8 (11%) were POLE mutated, 6 (8%) were MMR abnormal and 17 (23%) were p53 abnormal; the remaining 42 cases (58%) were p53 wild type (no POLE, p53 or MMR abnormalities). Mean follow-up period was 69 months (median 62, range 1-179). The molecular classification was an independent predictor for disease free and overall survival on multivariate analysis (p = 0.005 and 0.045 respectively, Cox proportional hazard model). POLE mutated and MMR abnormal groups had 100% 5 year DFS and OS. p53 wild type cases had intermediate survival rates (86% DFS and OS). Conversely, the p53 abnormal group had worse outcomes with 42% DFS and 76% OS at 5 years. Conclusions: OEC can be classified into prognostically distinct subgroups by testing for molecular surrogates, akin to endometrial cancer. MMR and POLE alterations seem to identify a subset of ovarian endometrioid carcinomas with excellent outcome; conversely, abnormal p53 expression carries a worse prognosis. In the era of personalized medicine, the use of these markers in the routine evaluation of ovarian endometrioid tumors should be considered.

Download Full-text

MicroRNA-17-92 Downregulates Expression of Distinct Targets in Different B-Cell Lymphoma Subtypes

Blood ◽

10.1182/blood.v112.11.5321.5321 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5321-5321

Author(s):

Hiroyuki Tagawa ◽

Mika Inomata ◽

Yong-Mei Guo ◽

Yoshihiro Kameoka ◽

Naoto Takahashi ◽

...

Keyword(s):

Cell Growth ◽

B Cell ◽

Cell Cycle Progression ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Homozygous Deletion ◽

P53 Expression ◽

Raji Cells ◽

Apoptotic Protein ◽

Mantle Cell

Abstract Aberrant overexpression of the miR-17-92 polycistron is strongly associated with B-cell lymphomagenesis. Recent studies have shown that miR-17-92 downregulates the pro-apoptotic protein Bim, leading to overexpression of Bcl2, which likely plays a key role in lymphomagenesis. However, the fact that Jeko-1 cells derived from mantle cell lymphoma exhibit both homozygous deletion of BIM and overexpression of miR-17-92 suggests other targets are also involved in B-cell lymphomagenesis. To identify essential target(s) of miR-17-92 in lymphomagenesis, we first transfected miR-17-92 into genetically distinct B-cell lymphoma cell lines, including Raji cells, which overexpress c-Myc, and SUDHL4 cells, which overexpress Bcl2. Raji cells transfected with miR- 17-19b exhibited downregulation of Bim and reversible upregulation of Bcl2. On the other hand, SUDHL4 cells transfected with miR-17-19b showed aggressive cell growth reflecting facilitated cell cycle progression at the G1-S transition, and decreased expression of CDKN1A mRNA and p21 protein (CDKN1A/p21) that was independent of p53 expression. Conversely, transfection of antisense oligonucleotides against miR-17 and miR-20a into Jeko-1 cells led to upregulation of CDKN1A/p21, resulting in decreased cell growth with G1-S arrest. Thus, CDKN1A/p21 appears to be an essential target of miR-17-92 during B-cell lymphomagenesis, which suggests the polycistron has distinct targets in different B-cell lymphoma subtypes.

Download Full-text

Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma

International Journal of Gynecological Cancer ◽

10.1046/j.1525-1438.2002.01079.x ◽

2002 ◽

Vol 12 (1) ◽

pp. 110-118 ◽

Cited By ~ 26

Author(s):

C. Lundgren ◽

G. Auer ◽

B. Frankendal ◽

B. Moberger ◽

B. Nilsson ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Dna Content ◽

Proliferative Activity ◽

Nuclear Dna ◽

Nuclear Dna Content ◽

P53 Expression ◽

Histopathologic Features

Download Full-text

Endometrioid Endometrial Carcinoma With Spindle Cells–Aberrant p16 and p53 Expression

International Journal of Surgical Pathology ◽

10.1177/1066896918781730 ◽

2018 ◽

Vol 27 (2) ◽

pp. 203-207

Author(s):

Snehal Sonawane ◽

Osama Elfituri ◽

Yanmin Zhang ◽

Edgardo Yordan ◽

Nicholas Ree

Keyword(s):

Endometrial Carcinoma ◽

Spindle Cell ◽

Tumor Type ◽

Immunohistochemical Expression ◽

Cell Component ◽

Diagnostic Dilemma ◽

P53 Overexpression ◽

P53 Expression ◽

Spindle Cells ◽

Endometrioid Endometrial Carcinoma

Endometrioid carcinoma is known for its diverse morphology and may pose a diagnostic dilemma when it presents with a spindle cell component. We present a case of a 65-year-old woman with postmenopausal bleeding. Physical examination showed a mass protruding from the external cervical os. The patient underwent biopsy followed by hysterectomy. Pathologic examination showed an endometrioid endometrial carcinoma with spindle cell differentiation arising in an endometrial polyp, which raised a variety of differential diagnoses. Prior reports of this tumor type showed nonaberrant immunohistochemical expression of p16 and p53. However, this case showed p16 and p53 overexpression indicating that there is a spectrum of these tumors.

Download Full-text