Giatromanolaki A, Sivridis E, Koukourakis M I, Harris A L, Gatter K C
Department of Pathology, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece.
Anticancer Res. 1998 Sep-Oct;18(5B):3689-93.
The role of p53 and bcl-2 apoptosis related proteins in the pathogenesis of endometrial cancer remains unclear. We immunohistochemically examined 133 surgically removed tumour specimens from patients with stage I endometrial cancer for p53 oncoprotein nuclear expression and bcl-2 cytoplasmic reactivity. 114/133 (86%) cases were of the endometrioid histological sub-type. A cut-off point of 10% of cells with strong reactivity was used for positivity. Positive p53 expression was observed in 12/133 (9%) and positive bcl-2 in 40/133 (30%) cases. p53 expression was not related to bcl-2 expression. No association of p53 and bcl-2 with depth of myometrial invasion, vascular invasion or histological grade was observed. However, continuous variable analysis revealed a trend of low grade cases to have a higher percentage of bcl-2 positive cells (16.3 + 27% vs. 7.8 + 16%; p = 0.09, unpaired two tailed t-test). Interestingly, a statistically significant association of p53 positivity with age was also observed (p = 0.03). A strong association of high grade with depth of myometrial invasion (p = 0.006) and vascular invasion (p = 0.0001) was also noticed. In addition, the presence of adenomyosis was also associated with low grade (p = 0.01) and absence of vascular invasion (p = 0.02). We conclude that although loss of bcl-2 protein expression and p53 mutant protein nuclear accumulation are early events in the endometrial cancer progression, histological grade and vascular invasion remain the most important factors defining local invasive behaviour of endometrial cancer.
p53和bcl-2凋亡相关蛋白在子宫内膜癌发病机制中的作用仍不清楚。我们采用免疫组织化学方法检测了133例I期子宫内膜癌患者手术切除的肿瘤标本中p53癌蛋白的核表达和bcl-2的细胞质反应性。133例中有114例(86%)为子宫内膜样组织学亚型。以10%具有强反应性的细胞作为阳性判断标准。133例中有12例(9%)p53表达阳性,40例(30%)bcl-2表达阳性。p53表达与bcl-2表达无关。未观察到p53和bcl-2与肌层浸润深度、血管浸润或组织学分级之间存在关联。然而,连续变量分析显示低级别病例有bcl-2阳性细胞百分比更高的趋势(16.3 + 27%对7.8 + 16%;p = 0.09,非配对双尾t检验)。有趣的是,还观察到p53阳性与年龄之间存在统计学显著关联(p = 0.03)。高级别与肌层浸润深度(p = 0.006)和血管浸润(p = 0.0001)之间也存在强关联。此外,子宫腺肌病的存在也与低级别(p = 0.01)和无血管浸润(p = 0.02)相关。我们得出结论,尽管bcl-2蛋白表达缺失和p53突变蛋白核积累是子宫内膜癌进展中的早期事件,但组织学分级和血管浸润仍然是定义子宫内膜癌局部侵袭行为的最重要因素。