Ciavattini A, Lucarini G, Castaldini C, Goteri G, Romanini C, Biagini G, Garzetti G G
Institute of Obstetrics and Gynecology, University of Ancona, Italy.
Anticancer Res. 1999 Nov-Dec;19(6B):5463-7.
The bcl-2 proto-oncogene codes for a protein which appears to block apoptosis. In our study, we examined bcl-2 protein expression in cervical squamous metaplasia, cervical intraepithelial neoplasia (CIN) and microinvasive squamous carcinoma with the aim of identifying a relationship between bcl-2 protein expression and neoplastic development and progression.
Cervical bioptic samples were obtained from 86 white women, selected consecutively from our Colposcopic Service from January 1993 to June 1994, because of abnormal pap- smear suspicious for cervical dysplasia and/or human papilloma virus (HPV) infection. Upon histologic evaluation, 41 women had CIN, 23 cervical condyloma, and 22 squamous metaplasia. Ten patients with microinvasive squamous carcinoma, matched for age and demographic characteristics, were selected from our series of invasive cervical carcinomas and immunohistochemically analyzed. The expression of primary tumor bcl-2 protein was immunohistochemically evaluated by antihuman bcl-2 monoclonal antibody (diluted 1:100, Dako, Copenhagen, Denmark) on formalin-fixed paraffin-embedded tissue. Positive staining was expressed as a percentage of positive cells per 1000 counted dysplastic cells for each case.
Bcl-2 immunostaining was found in all the 22 squamous metaplasias, limited to the basal layer. Nineteen of the 41 CINs (46%) were bcl-2 immunoreactive, and 2 of the 10 microinvasive carcinomas (20%). By analysing CIN lesions, the bcl-2 protein showed a striking increase in the rate of positivity with increasing severity of CIN; the bcl-2 protein expression in CINs III was significantly higher than for CINs I, CINs II or microinvasive carcinomas (P = 0.03, P = 0.02, and P = 0.03 respectively). No relationship was observed between bcl-2 immunostaining and HPV infection. bcl-2 protein expression was not useful for predicting CIN I and II evolution, although the rate of persistence/progression was higher in bcl-2 positive dysplasias (7 of 9 cases, 78%) than in negative ones (13 of 21 cases, 62%) (p = 0.88).
Based on these results, it seems possible that the increase in bcl-2 expression in higher grade of CINs implies an increasing protection against programmed cell death, but also the induction of genetic instability in dysplastic epithelial cells and a greater capacity to evolve into invasive carcinoma.
bcl - 2原癌基因编码一种似乎能阻止细胞凋亡的蛋白质。在我们的研究中，我们检测了宫颈鳞状化生、宫颈上皮内瘤变（CIN）和微浸润性鳞状细胞癌中的bcl - 2蛋白表达，目的是确定bcl - 2蛋白表达与肿瘤发生发展之间的关系。
从1993年1月至1994年6月连续从我们的阴道镜检查服务中选取86名白人女性的宫颈活检样本，这些女性因巴氏涂片异常怀疑宫颈发育异常和/或人乳头瘤病毒（HPV）感染。经组织学评估，41名女性患有CIN，23名患有宫颈湿疣，22名患有鳞状化生。从我们的浸润性宫颈癌系列中选取10名年龄和人口统计学特征匹配的微浸润性鳞状细胞癌患者，并进行免疫组化分析。通过抗人bcl - 2单克隆抗体（稀释1:100，丹麦哥本哈根达科公司）对福尔马林固定石蜡包埋组织进行免疫组化评估原发性肿瘤bcl - 2蛋白的表达。阳性染色以每例每1000个计数的发育异常细胞中阳性细胞的百分比表示。
在所有22例鳞状化生中均发现bcl - 2免疫染色，仅限于基底层。41例CIN中有19例（46%）bcl - 2免疫反应阳性，10例微浸润癌中有2例（20%）阳性。通过分析CIN病变，随着CIN严重程度的增加，bcl - 2蛋白阳性率显著增加；CIN III中的bcl - 2蛋白表达明显高于CIN I、CIN II或微浸润癌（分别为P = 0.03、P = 0.02和P = 0.03）。未观察到bcl - 2免疫染色与HPV感染之间的关系。bcl - 2蛋白表达对预测CIN I和II的进展无用，尽管bcl - 2阳性发育异常的持续/进展率（9例中的7例，78%）高于阴性者（21例中的13例，62%）（p = 0.88）。
基于这些结果，似乎有可能在高级别CIN中bcl - 2表达的增加意味着对程序性细胞死亡的保护增加，但也意味着发育异常的上皮细胞中基因不稳定性的诱导以及发展为浸润性癌的更大能力。
