Garzetti G G, Ciavattini A, De Nictolis M, Lucarini G, Goteri G, Romanini C, Biagini G
Institute of Gynecology and Obstetrics, University of Ancona, Italy.
Gynecol Obstet Invest. 1996;42(4):261-6. doi: 10.1159/000291977.
MIB 1 is a new monoclonal antibody which recognizes nuclei of proliferating cells throughout the cell cycle except during the G0 and early G1 phases. In the present study we analyzed the MIB 1 immunostaining as an index of cellular proliferation in cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma, with the aim to identify a relationship with the degree of dysplastic lesion and the risk of neoplastic progression. A correlation between the MIB 1 index and human papillomavirus (HPV) DNA presence was also investigated
Cervical bioptic samples were consecutively obtained from 86 women who attended our Colposcopic Service from January 1993 to June 1994, because of abnormal pap smears suspicious for cervical dysplasia and/or HPV infection. On histologic evaluation, 41 women had CIN, 23 cervical condyloma, and 22 squamous metaplasia. Ten patients with microinvasive squamous cervical carcinoma, matched for age and demographic characteristics, were selected from our series of cervical carcinomas and immunohistochemically analyzed. The expression of primary tumor cellular proliferation was immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave oven-processed formalin-fixed paraffin-embedded tissue. Positive staining was expressed as the percentage of positive cells per 10(3) counted dysplastic cells for each case.
A progressive significant increase in positive MIB 1 immunostaining was observed from squamous metaplasia to microinvasive carcinoma throughout the CIN lesions (p < 0.001). Considering only CINs, the MIB 1 index showed a significant increase with respect to CIN degrees (p < 0.001); no correlation was found between MIB 1 immunostaining and HPV infection, and lesion size. By analyzing the MIB 1 index with respect to CIN outcome in mild and moderate dysplasias, regressive lesions had lower values of MIB 1 immunostaining, while persistent and progressive lesions presented significantly higher positivity (p < 0.001).
Our data demonstrated: (1) that positive MIB 1 immunostaining increased progressively from squamous metaplasia to CIN and microinvasive carcinoma, suggesting that neoplastic transformation is associated with a dysfunctional proliferation of cervical epithelium; (2) that there was a significant correlation between the MIB 1 index and CIN degree but not with respect to HPV DNA presence, and (3) that MIB 1 immunostaining might be useful for a clinical evaluation of mild and moderate dysplastic lesions. However, a much larger study needs to be done over a longer period of time to truly determine the value of the technique in prognostically predicting which lesions might or might not regress.
MIB 1是一种新型单克隆抗体，可识别整个细胞周期中增殖细胞核，但G0期和G1早期除外。在本研究中，我们分析了MIB 1免疫染色作为宫颈上皮内瘤变（CIN）和微浸润癌中细胞增殖的指标，旨在确定其与发育异常病变程度及肿瘤进展风险之间的关系。还研究了MIB 1指数与人类乳头瘤病毒（HPV）DNA存在情况之间的相关性。
1993年1月至1994年6月期间，连续从86名因巴氏涂片异常怀疑宫颈发育异常和/或HPV感染而前来我们阴道镜服务中心就诊的女性中获取宫颈活检样本。组织学评估显示，41名女性患有CIN，23名患有宫颈湿疣，22名患有鳞状化生。从我们的宫颈癌系列中挑选出10名年龄和人口统计学特征匹配的微浸润性鳞状宫颈癌患者，并进行免疫组织化学分析。通过单克隆MIB 1抗体（Immunotech，法国马赛赛德克斯）对经微波炉处理的福尔马林固定石蜡包埋组织进行免疫组织化学评估原发性肿瘤细胞增殖的表达。阳性染色表示为每例中每10³个计数的发育异常细胞中阳性细胞的百分比。
在整个CIN病变中，从鳞状化生到微浸润癌，观察到MIB 1免疫染色阳性呈逐渐显著增加（p < 0.001）。仅考虑CIN时，MIB 1指数随CIN程度显著增加（p < 0.001）；未发现MIB 1免疫染色与HPV感染及病变大小之间存在相关性。通过分析轻度和中度发育异常中MIB 1指数与CIN转归的关系，消退性病变的MIB 1免疫染色值较低，而持续性和进行性病变的阳性率显著更高（p < 0.001）。
我们的数据表明：（1）从鳞状化生到CIN和微浸润癌，MIB 1免疫染色阳性逐渐增加，提示肿瘤转化与宫颈上皮细胞增殖功能失调有关；（2）MIB 1指数与CIN程度显著相关，但与HPV DNA存在情况无关；（3）MIB 1免疫染色可能有助于对轻度和中度发育异常病变进行临床评估。然而，需要在更长时间内进行更大规模的研究，以真正确定该技术在预测哪些病变可能消退或不会消退方面的预后价值。
