Bcl-2 expression and prognosis of patients with endometrial carcinoma

Sakuragi, Noriaki; Ohkouchi, Toshihiro; Hareyama, Hitoshi; Ikeda, Ken; Watari, Hidemichi; Fujimoto, Toshio; Kuwabara, Makoto; Yamamoto, Ritsu; Sagawa, Tadashi; Fujino, Takafumi; Fujimoto, Seiichiro

doi:10.1002/(sici)1097-0215(19980417)79:2<153::aid-ijc10>3.0.co;2-b

Cited by 34 publications

(26 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, the usefulness of induction of apoptosis after irradiation therapy as a predictor of short-term prognosis has been reported in patients with cancer other than uterine cancer. 8,[20][21][22][23] In uterine cervical cancer, similar observations were reported. 7,24) However, it has not been established whether apoptosis after initial irradiation dose delivery can predict long-term prognosis.…”

Section: Discussionsupporting

confidence: 63%

Detection of Apoptosis and Expression of Apoptosis‐associated Proteins as Early Predictors of Prognosis after Irradiation Therapy in Stage IIIb Uterine Cervical Cancer

Yuki

Fujimura

Yamakawa

et al. 2000

Japanese Journal of Cancer Research

View full text Add to dashboard Cite

We investigated the proportion of apoptotic cells and the expression of apoptosis-associated proteins after the delivery of the first week of irradiation for stage IIIb uterine cervical cancer. Thirty patients with stage IIIb squamous cell carcinoma of the uterine cervix who received only irradiation therapy were registered in this study. Specimens were obtained before irradiation therapy and at the end of the first week of irradiation. The apoptotic index (AI) of each tissue specimen was calculated by counting the apoptotic cells and expressed as a percentage. Immunohistochemical evaluation for apoptosis-related proteins, p53, Bcl-2, Bax, caspase-1 and caspase-3 was also performed. The AI was 0.8 ± ± ± ±0.9% (mean ± ± ± ± SD) before irradiation and 1.7 ± ± ± ±1.3% at the end of the first week of irradiation. We observed that the patients who survived more than 5 years had AI levels of 2.1 ± ± ± ±1.3% at the end of their first week of therapy. This rate was significantly higher than the rate of 1.1 ± ± ± ±0.8% (P = = = =0.02) of the patients who died within 5 years. When the cut-off value of the AI was set at 1.7%, the sensitivity, specificity, positive predictive value, and negative predictive value for the prediction of patients' prognosis after irradiation therapy were 73.4%, 72.4%, 82.4%, and 61.5%, respectively. In 17 of the AI-positive cases, expressions of Bax (P = = = =0.006), caspase-1 (P = = = =0.045), and caspase-3 (P = = = =0.013) at the end of the first week were significantly higher than before irradiation. The proportion of apoptotic cells and the expression of apoptosis-associated proteins, Bax, caspase-1, and caspase-3, at the end of the first week of irradiation could be useful predictors of the prognosis in stage IIIb squamous cell carcinoma of the uterine cervix treated by irradiation therapy.

show abstract

Section: Discussionsupporting

confidence: 63%

Detection of Apoptosis and Expression of Apoptosis‐associated Proteins as Early Predictors of Prognosis after Irradiation Therapy in Stage IIIb Uterine Cervical Cancer

Yuki

Fujimura

Yamakawa

et al. 2000

Japanese Journal of Cancer Research

View full text Add to dashboard Cite

show abstract

“…This might explain why Bcl-2 expression is associated with poor prognosis in several types of malignancies (Sakuragi et al, 1998). Our study is the ®rst to report the anti-apoptotic mechanism of Bcl-2 upregulation by ADM. Others have recently demonstrated other pathways: ADM antagonizes serum-deprivation-induced endothelial apoptosis by upregulation of the transcription factor Max, the heterodimeric partner of c-Myc (Shichiri et al, 1999).…”

Section: Discussionmentioning

confidence: 67%

Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth

et al. 2001

View full text Add to dashboard Cite

Regions of hypoxia are a common feature of solid tumours. When tumour cells are exposed to hypoxic stress, transcription of a battery of genes is initiated. The angiogenic factor adrenomedullin (ADM) is a hypoxia regulated gene. ADM is thought to act through the G protein-coupled receptor calcitonin receptor-like receptor (CRLR), with speci®city being conferred by the receptor associated modifying protein 2 (RAMP2). Here we report for the ®rst time that ADM treated or stably transfected Ishikawa cells overexpressing ADM show increased resistance to hypoxia induced apoptosis. These cells also show an upregulation of the oncoprotein Bcl-2, which is protective against hypoxic cell death when transiently transfected into Ishikawa cells. Since Ishikawa cells express the putative ADM-receptor CRLR ± RAMP2 the production and secretion of ADM with the consecutive upregulation of Bcl-2 could establish an autocrine/ paracrine mechanism rescuing malignant cells from hypoxic cell death. These results, taken together with our previous ®ndings that ADM is an angiogenic factor which is upregulated by the nonsteroidal antiestrogen tamoxifen (TAM) in endometrial cells, implicate this peptide as a promoter of tumour growth and a possible target for anticancer strategies. Oncogene (2001) 20, 2937 ± 2945.

show abstract

“…We stained a series of cases of endometrial carcinoma seen consecutively at our center with a panel of antibodies. This panel was chosen primarily based on their known role in endometrial carcinogenesis or previously demonstrated significance as prognostic markers in endometrial carcinoma (p53, 26,36 PTEN, 37,38 ER and PR, 39,40 bcl-2, 41-43 HER2 41,44,45 ) or their role in cell-cycle regulation (p21, p27, E2F-1) (reviewed in Israels and Israels 46 ). We did not use MIB-1 (Ki67) immunostaining as we have previously shown that it shows only a weak correlation with mitotic activity in uterine serous carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostically relevant and reproducible subsets of endometrial adenocarcinoma based on clustering analysis of immunostaining data

et al. 2007

View full text Add to dashboard Cite

Panels of immunomarkers can provide greater information than single markers, but the problem of how to optimally interpret data from multiple immunomarkers is unresolved. We examined the expression profile of 12 immunomarkers in 200 endometrial carcinomas using a tissue microarray. The outcomes of groups of patients were analyzed by using the Kaplan-Meier method, using the log-rank statistic for comparison of survival curves. Correlation between clustering results and traditional prognosticators of endometrial carcinoma was examined by either Fisher's exact test or v 2 -test. Multivariate analysis was performed using a proportional hazards method (Cox regression modeling). Seven of the 12 immunomarkers studied showed prognostic significance in univariate analysis (Po0.05) and 1 marker showed a trend toward significance (P ¼ 0.06). These eight markers were used in unsupervised hierarchical clustering of the cases, and resulted in identification of three cluster groups. There was a statistically significant difference in patient survival between these cluster groups (P ¼ 0.0001). The prognostic significance of the cluster groups was independent of tumor stage and patient age on multivariate analysis (P ¼ 0.014), but was not of independent significance when either tumor grade or cell type was added to the model. The cluster group designation was strongly correlated with tumor grade, stage, and cell type (Po0.0001 for each). Interlaboratory reproducibility of subclassification of endometrial adenocarcinoma by hierarchical clustering analysis was verified by showing highly reproducible assignment of individual cases to specific cluster groups when the immunostaining was performed, interpreted, and clustered in a second laboratory (j ¼ 0.79, concordance rate ¼ 89.6%). Unsupervised hierarchical clustering of immunostaining data identifies prognostically relevant subsets of endometrial adenocarcinoma. Such analysis is reproducible, showing less interobserver variability than histopathological assessment of tumor cell type or grade.

show abstract

Bcl-2 expression and prognosis of patients with endometrial carcinoma

Cited by 34 publications

References 22 publications

Detection of Apoptosis and Expression of Apoptosis‐associated Proteins as Early Predictors of Prognosis after Irradiation Therapy in Stage IIIb Uterine Cervical Cancer

Detection of Apoptosis and Expression of Apoptosis‐associated Proteins as Early Predictors of Prognosis after Irradiation Therapy in Stage IIIb Uterine Cervical Cancer

Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth

Identification of prognostically relevant and reproducible subsets of endometrial adenocarcinoma based on clustering analysis of immunostaining data

Contact Info

Product

Resources

About