Garzetti G G, Ciavattini A, Lucarini G, Goteri G, Nictolis M D, Romanini C, Biagini G
Instituto di Clinica Ostetrica e Ginecologica, Università degli Studi di Ancona, Italy.
Anticancer Res. 1998 Jan-Feb;18(1B):609-13.
Ras p21 expression seems to be associated with aggressiveness of neoplastic growth and metastatic potentially in human solid tumors. In our series of early-stage squamous cervical carcinoma, we evaluated ras p21 expression with respect to lymph nodal involvement; the aim was to analyse the ras p21 immunostaining as potential marker of lymphatic spread, and investigate the relationship between ras p21 expression and 72 kDa-metalloproteinase immunostaining.
46 patients with FIGO stage I squamous cell cervical carcinoma, who had undergone primary radical surgery with systematic pelvic and paraaortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, were recruited from our series of 59 consecutive cases, and included the study. Any characteristic that could be relevant for prognosis was recorded such as: histologic grade of differentiation, tumor size, lymphatic spread, or adjuvant radiotherapy. Immunohistochemical staining was performed using the avidin-biotin peroxidase complex method (LSAB, Dako, Copenhagen, Denmark). Monoclonal antibody anti-pan ras (Ab-1) (Oncogene Science) and affinity purified rabbit anti-72 kDa-metalloproteinase antibody were used. Positivity for ras p21 was evaluated by semiquantitative analysis, while 72 kDa-metalloproteinase staining was expressed as the percentage of positive cells per 10(3) counted neoplastic cells (index).
The expression of ras p21 was observed in 31 patients (67%) with FIGO stage I squamous cervical carcinoma. No connection was found between ras p21 expression and tumor size (P = 0.2), or histologic grade (P = 0.9), while a significant relationship was observed with respect to lymph nodal status (p = 0.048). By analysing 72 kDa-metalloproteinase immunostaining, ras p21 positive carcinomas showed significantly higher 72 kDa-metalloproteinase index than the negative ones (mean + standard deviation, 23.3% + 7.7% and 13.8% + 5.1% respectively, and P < 0.001).
Though the relatively small size of our series does not allow any definitive conclusion, a significant relationship between ras p21 expression and risk of lymphatic spread was detected in early-stage cervical carcinoma. ras p21 positivity seems to be an indicator of neoplastic aggressiveness and lymphatic spread, and is associated with significantly higher expression of 72 kDa-metalloproteinase.
在人类实体瘤中，Ras p21表达似乎与肿瘤生长的侵袭性及转移潜能相关。在我们的早期宫颈鳞状细胞癌系列研究中，我们评估了Ras p21表达与淋巴结受累情况；目的是分析Ras p21免疫染色作为淋巴转移潜在标志物的情况，并研究Ras p21表达与72 kDa金属蛋白酶免疫染色之间的关系。
从我们连续的59例病例系列中选取46例国际妇产科联盟（FIGO）I期宫颈鳞状细胞癌患者，这些患者在安科纳大学妇产科研究所接受了系统性盆腔和腹主动脉旁淋巴结清扫的根治性手术（Piver III型），并纳入研究。记录任何可能与预后相关的特征，如：组织学分化程度、肿瘤大小、淋巴转移或辅助放疗。采用抗生物素蛋白-生物素过氧化物酶复合物法（LSAB，丹麦哥本哈根达科公司）进行免疫组织化学染色。使用抗泛Ras单克隆抗体（Ab-1）（癌基因科学公司）和亲和纯化的兔抗72 kDa金属蛋白酶抗体。通过半定量分析评估Ras p21的阳性情况，而72 kDa金属蛋白酶染色则以每10³个计数肿瘤细胞中阳性细胞的百分比表示（指数）。
在46例FIGO I期宫颈鳞状细胞癌患者中，31例（67%）观察到Ras p21表达。未发现Ras p21表达与肿瘤大小（P = 0.2）或组织学分级（P = 0.9）之间存在关联，而与淋巴结状态存在显著关系（P = 0.048）。通过分析72 kDa金属蛋白酶免疫染色，Ras p21阳性的癌组织显示出的72 kDa金属蛋白酶指数显著高于阴性组织（分别为平均值±标准差，23.3%±7.7%和13.8%±5.1%，P < 0.001）。
尽管我们的系列研究规模相对较小，无法得出任何确定性结论，但在早期宫颈癌中检测到Ras p21表达与淋巴转移风险之间存在显著关系。Ras p21阳性似乎是肿瘤侵袭性和淋巴转移的一个指标，并且与72 kDa金属蛋白酶的显著高表达相关。
