bcl-2 Expression in Endometrial Hyperplasia and Carcinoma

Niemann, Theodore H.; Trgovac, Tracey L.; McGaughy, Violeta R.; Vaccarello, Luis

doi:10.1006/gyno.1996.0329

Cited by 30 publications

(28 citation statements)

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“…Although no difference was noted in the frequency of bcl-2 expression in UEA and UPSA (65 versus 66.5%), UPSA showed less intense and more heterogeneous expression of this marker than did UEA. In agreement with this observation are the reports of Niemann et al (58) and Zheng et al (28). Although bcl-2 expression in the current study was more frequent in low-grade endometrioid carcinomas, this difference was not statistically significant.…”

Section: Discussionsupporting

confidence: 91%

“…Although bcl-2 expression in the current study was more frequent in low-grade endometrioid carcinomas, this difference was not statistically significant. Most of the previous reports showed higher incidence of bcl-2 positivity in well-differentiated tumors, but some found no association between bcl-2 expression and histologic grade (55,58). In our study, bcl-2 expression was also associated with earlystage endometrioid tumors (75 versus 55%) and the difference was very close to the limit of statistical significance (p ϭ .07).…”

Section: Discussionsupporting

confidence: 68%

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Immunohistochemical Profile of Endometrial Adenocarcinoma: A Study of 61 Cases and Review of the Literature

et al. 2000

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The differences in immunohistochemical expression of p53, bcl-2, bax, estrogen receptor (ER), and progesterone receptor (PR) were evaluated in 40 endometrioid and 21 papillary serous carcinomas of endometrium and correlated with known predictors of survival, such as grade and stage. Uterine papillary serous adenocarcinomas (UPSA) showed significantly higher p53 expression than did uterine endometrioid adenocarcinomas (UEA) (76.2% versus 35%), whereas both ER and PR were more often positive in endometrioid than in serous tumors (p ‫؍‬ .005 and .0005). No significant difference was found in bcl-2 and bax expression between both histologic types. However, there was definite decrease in intensity of bcl-2 in UPSA compared with UEA. In endometrioid carcinoma, p53 overexpression was associated with high-grade and advanced-stage tumors (p ‫؍‬ .0006 and .006), whereas ER and PR expression was associated with low-grade and earlystage tumors (p ‫؍‬ .0006 and .0001; p ‫؍‬ .003 and .0006). Bcl-2 immunopositivity was more common in low-grade, early-stage rather than in high-grade, advanced-stage adenocarcinomas, but the difference was not statistically significant (p ‫؍‬ .24 and .07). Bax immunopositivity was associated with well-differentiated (p ‫؍‬ .04) and early-stage tumors. Furthermore, a significant inverse relationship between bax and p53 reactivity was defined (p ‫؍‬ .05), especially in tumors of endometrioid type. Bax and PR immunoexpression correlated near the limit of statistical significance (p ‫؍‬ .08), whereas no relationship was found among bax, bcl-2, and ER Endometrial adenocarcinoma (EA) is the most common gynecologic malignancy (1). Traditional factors associated with its prognosis include patient's age, tumor grade, stage, histologic type, and the depth of myometrial invasion. Two histologic types of EA-endometrioid and papillary serousare associated with different biologic behavior (2, 3). Uterine endometrioid adenocarcinomas (UEA) are usually accompanied by endometrial hyperplasia and typically are low grade, are early stage, and have favorable prognosis. Uterine papillary serous adenocarcinomas (UPSA) usually develop in an atrophic endometrium; are high grade; are advanced stage, and do not respond to conventional chemotherapy, radiotherapy, and hormone therapy (4, 5). Recently, a dualistic model of carcinogenesis has been proposed on the basis of the distinctive clinical and histologic features of endometrioid and serous adenocarcinoma (6). Based on this model, UEA is associated with a slow, estrogen-driven model of carcinogenesis whereby unopposed estrogen stimulation leads to the sequential malignant transformation through a stage of atypical endometrial hyperplasia. In contrast, a p53-driven model of

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 68%

Immunohistochemical Profile of Endometrial Adenocarcinoma: A Study of 61 Cases and Review of the Literature

et al. 2000

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“…33 In the current study the expression of Bcl-2 was similar to that described previously, showing a decreasing pattern from normal endometrium to hyperplasia and further to carcinoma. 34 In different malignancies, Bcl-2 is thought to protect cells from apoptotic signals. 42 In endometrial hyperplasia and cancer this concept does not seem to be that clear.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis and apoptosis‐related factors Bcl‐2, Bax, tumor necrosis factor‐α, and NF‐κB in human endometrial hyperplasia and carcinoma

Vaskivuo

Stenbäck

Tapanainen

2002

Cancer

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BACKGROUNDApoptosis controls cell homeostasis in the endometrium during normal menstrual cycles, and morphologic studies have suggested its association with the development of endometrial carcinoma. Apoptosis is regulated by several genes, especially those of the Bcl‐2 gene family, but their significance in endometrial pathologies is not well understood.METHODSTo study the role and regulation of apoptosis in endometrial hyperplasia and carcinoma, human endometrial specimens were analyzed using in situ 3′‐end labeling of apoptotic cells and in situ hybridization and immunohistochemistry of apoptosis‐related factors.RESULTSApoptosis was scarce in normal proliferating endometrium as well as in simplex, complex, and atypical hyperplasia and was low in Grade I adenocarcinoma. In Grade II adenocarcinoma a significant increase in the rate of apoptosis was observed. Apoptosis decreased in Grade III adenocarcinoma, but it was still higher than in normal or hyperplastic endometrium. Bcl‐2 and Bax were expressed in normal and hyperplastic endometrium, and the Bcl‐2/Bax ratio was lower in endometrial carcinoma. Tumor necrosis factor‐α was expressed in normal endometrium and simplex and complex hyperplasia, but it was down‐regulated in atypical hyperplasia and endometrial carcinoma. The transcription factor NF‐κB was present in proliferating endometrium and in endometrial hyperplasia, but its expression was lower in carcinoma.CONCLUSIONSIn endometrial proliferation and hyperplasia a low rate of apoptosis is present. In Grade I carcinoma the rate of apoptosis is decreased, but the rate is subsequently increased in advanced carcinoma. The decrease in the rate of apoptosis in Grade III adenocarcinoma may reflect loss of control of cell homeostasis, decreased differentiation, and increased malignancy. Cancer 2002;95:1463–71. © 2002 American Cancer Society.DOI 10.1002/cncr.10876

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“…However, no specific function has been attributed to these various locations [26]. Niemann et al [27] and Vinatier et al [28] explained the formation of endometrial polyps. There may be a prolonged excessive expression of Bcl-2 in one particular area of the endometrium, allowing the epithelial cells to escape the normal programmed cell death, allowing clonal expansion, without the expected increase in proliferation index or cell turnover.…”

Section: Discussionmentioning

confidence: 99%

Expression of Bcl-2 and Ki-67 in Tamoxifen-Associated Endometrial Polyps: Comparison with Postmenopausal Polyps

et al. 2006

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Background: The aim of this study was to evaluate the expression of Bcl-2 and Ki-67 in tamoxifen (TAM)-associated endometrial polyps and postmenopausal polyps. Material and Methods: For this purpose, a retrospective analysis of paraffin-embedded specimens was carried out. Polyps of 20 postmenopausal and 14 TAM-treated patients, 11 simple endometrial hyperplasia, 10 atypical complex endometrial hyperplasia and 8 endometrial adenocarcinoma specimens were included in the study. Hematoxylin/eosin-stained sections were evaluated. Immunohistochemical staining was performed to investigate the expression of Bcl-2 protein and the Ki-67 proliferation index. Results: There was no statistically significant difference between the 5 groups with regard to Bcl- 2 staining (p > 0.05). However, Bcl-2 expression in TAM-associated polyps was higher (86%) than in the postmenopausal control group (80%). Positive Ki-67 was highest in the endometrial adenocarcinoma specimens, followed by the atypical complex endometrial hyperplasia group (p < 0.0001). Compared to these 2 groups, Ki- 67 expression was lower in TAM-associated polyps, but Ki-67 indexes were significantly higher in the TAM-associated group than in the control group (p < 0.0001). Conclusion: Since TAM-associated polyps tend to have higher proliferation indexes and Ki-67 ratios than control groups, we suggest that they are likely to have a higher malignant potential.

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bcl-2 Expression in Endometrial Hyperplasia and Carcinoma

Cited by 30 publications

References 5 publications

Immunohistochemical Profile of Endometrial Adenocarcinoma: A Study of 61 Cases and Review of the Literature

Immunohistochemical Profile of Endometrial Adenocarcinoma: A Study of 61 Cases and Review of the Literature

Apoptosis and apoptosis‐related factors Bcl‐2, Bax, tumor necrosis factor‐α, and NF‐κB in human endometrial hyperplasia and carcinoma

Expression of Bcl-2 and Ki-67 in Tamoxifen-Associated Endometrial Polyps: Comparison with Postmenopausal Polyps

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