Immunohistochemical Analysis of Endometrial Adenocarcinoma for bcl-2 and p53 in Relation to Expression of Sex Steroid Receptor and Proliferative Activity

Yamauchi, Naoko; Sakamoto, Atsuhiko; Uozaki, Hiroshi; Iihara, Kuniko; Machinami, Rikuo

doi:10.1097/00004347-199610000-00015

Cited by 12 publications

(24 citation statements)

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“…A selective correlation of mdm-2 expression with p53 expression in UEA was previously reported, whereas such a correlation was not found in UPSA (42). The absence of p53 alterations in atypical hyperplasia and significantly higher p53 immunopositivity in high-grade and advanced-stage UEA in the current study sup- port the late occurrence of p53 alterations in the pathogenesis of endometrioid tumors (26,29,32,33,(43)(44)(45)(46)(47). In serous tumors, the reported identification of p53 overexpression and gene mutation in endometrial intraepithelial carcinoma, a recently identified precursor of UPSA (48,49) as well as in early-stage UPSA (28), support the early occurrence of p53 alterations.…”

Section: Discussionsupporting

confidence: 59%

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: 59%

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

et al. 2000

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“…MIB-1 is a monoclonal antibody that recognizes a nuclear antigen that is expressed in all cell cycle phases except G 0 . MIB-1 monoclonal antibody is a reliable means of assessing the growth fraction of normal tissues and has been used to study the cell proliferation in various cancers (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Markers of Proliferative Activity Are Predictors of Patient Outcome for Low-Grade Endometrioid Adenocarcinoma But Not Papillary Serous Carcinoma of Endometrium

et al. 2002

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On the basis of pathogenesis, two types of endometrial cancer can be recognized. Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogen stimulation, on a background of endometrial hyperplasia. Type 2 endometrial carcinomas are aggressive tumors that are not associated with hyperplasia or estrogen excess. The aim of this study is to evaluate the prognostic significance of tumor proliferative activity in early-stage endometrial cancer by using mitotic index and immunostaining, comparing Type 1 (endometrioid) and Type 2 (papillary serous carcinoma) tumors. The mitotic index, MIB-1, and p53 immunostaining in 39 tumors from patients with lowgrade Stage Ia or Ib endometrioid adenocarcinoma; as well as 23 tumors from patients with Stage I papillary serous carcinoma. In low-grade endometrioid adenocarcinoma, mitotic and MIB-1 indices were statistically significant independent prognostic indicators (P ‫؍‬ .004 and P ‫؍‬ .018, respectively), and both were strongly correlated with p53 expression (P ‫؍‬ .01 and P ‫؍‬ .006, respectively). The mean mitotic index was 5 mitoses/10 high-power fields, and mean MIB-1 index was 27.5%. There was no significant correlation between mitotic or MIB-1 indices and patient outcome or p53 expression in papillary serous carcinoma. The mean mitotic index was 31 mitoses/10 high-power fields, and mean MIB-1 index was 30.5% in these tumors. p53 expression and proliferative indices are strongly correlated in low-grade endometrioid adenocarcinoma. MIB-1 and mitotic indices are independent prognostic indicators in these tumors. Papillary serous carcinoma of endometrium is rapidly proliferative in tumors even at an early stage, and quantification of proliferative activity in these tumors does not allow prediction of patient outcome. KEY WORDS: Endometrial carcinoma, MIB-1, Mitotic index, p53, Papillary serous carcinoma, Proliferative activity. Mod Pathol 2002;15(4):365-371Endometrial cancer is the fourth most common malignancy in North American women. In the United States, there are 33,000 newly diagnosed cases and 4,000 deaths per year (1, 2). On the basis of the proposed dualistic model of endometrial carcinogenesis, there are two types of endometrial carcinoma that differ with regard to epidemiologic risk factors, histopathologic lesions, and molecular events (3). Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogenic stimulation. Low-grade endometrioid adenocarcinoma is the prototype of Type 1 endometrial carcinoma. Although most of these patients do well, recurrence and death due to disease can occur. Type 2 endometrial carcinomas are more aggressive tumors that are not associated with endometrial hyperplasia or estrogen excess. These tumors develop de novo in the atrophic endometrium of older postmenopausal women (4 -7). Papillary serous carcinoma of endometrium (PSCE) is the prototype of Type 2 endometrial carcinoma and is an uncommon aggressive variant of endometrial cancer. It accounts for 1-10% of cas...

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“…The histologic appearance of the endometrium was classified as M = menstruation (days 1-5), EP = early proliferative (days 6-9), LP = late proliferative (days [10][11][12][13][14], ES = early secretory (days [15][16][17][18], MS = mid-secretory (days [19][20][21][22] and LS = late secretory (days 23-28) phase. For each of these phases specimens from 5 representative uteri were collected.…”

Section: Uterine Tissue Samplesmentioning

confidence: 99%

The Expression of Apoptosis-Related Proteins Bcl-2 and Ki67 in Endometrium of Ovulatory Menstrual Cycles

Mertens¹,

Heineman²,

Evers³

2002

Gynecol Obstet Invest

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Background: During the menstrual cycle, a rapid sequence of proliferation, differentiation and cell death occurs in the human endometrium. Mechanisms involved in cell proliferation have been studied extensively. Apoptosis has recently been recognized to be a physiologic phenomenon. The aim of this study was to investigate the mechanisms involved in hormone-dependent tissue remodeling by measuring Bcl-2, an apoptosis inhibitor, and Ki67, a proliferation marker, as expressed in normal human endometrium. Methods: Paraffin-embedded endometrial sections of 30 uteri were immunostained for Bcl-2 and Ki67; expression was scored in cavitary epithelium, functional and basal glandular epithelial and stromal cells of the endometrium. Results: Bcl-2 expression increased in the proliferative phases and decreased significantly in the secretory phases, especially in glandular epithelial cells (131 ± 45 for functional laminal cells and 227 ± 68 for basal laminal cells to 0). Ki67 expression showed the same cyclic pattern with a later onset (145 ± 63 for functional laminal cells and 13 ± 8 for basal laminal cells to 0). Conclusion: Bcl-2 promotes cell survival by preventing apoptosis. Proliferation is the result of increasing estradiol concentration, high estrogen receptor expression and growth hormones and high Bcl-2 and Ki67 expression. After the onset of progesterone production, Bcl-2 levels decrease and Ki67 levels and androgen receptor expression in stromal cells disappear resulting in cell disintegration and menstruation. Persistent Bcl-2 expression, like we saw in basal laminal stromal and epithelial cells, accounts for the privilege of escaping from apoptosis-inducing signals. This allows reconstruction of the functional endometrium from its preserved basal layer after menstruation.

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Immunohistochemical Analysis of Endometrial Adenocarcinoma for bcl-2 and p53 in Relation to Expression of Sex Steroid Receptor and Proliferative Activity

Cited by 12 publications

References 0 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

Markers of Proliferative Activity Are Predictors of Patient Outcome for Low-Grade Endometrioid Adenocarcinoma But Not Papillary Serous Carcinoma of Endometrium

The Expression of Apoptosis-Related Proteins Bcl-2 and Ki67 in Endometrium of Ovulatory Menstrual Cycles

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