Davidson B, Nesland J M, Goldberg I, Kopolovic J, Gotlieb W H, Bryne M, Ben-Baruch G, Berner A, Reich R
Department of Pathology, The Norwegian Radium Hospital, Montebello, Oslo N-0310, Norway.
Gynecol Oncol. 2001 May;81(2):166-71. doi: 10.1006/gyno.2001.6156.
The aim of this study was to analyze the correlation among the expression of caveolin-1, the protein constituent of caveolae, and disease outcome in advanced-stage ovarian carcinomas.
Sections from 76 primary ovarian carcinomas and metastatic lesions from 45 patients diagnosed with advanced-stage ovarian carcinoma (FIGO stages III-IV) were evaluated for caveolin-1 expression using immunohistochemistry. Patients were divided into long-term survivors and short-term survivors based on disease outcome. Twenty nonneoplastic fallopian tubes and ovaries were additionally studied.
The mean follow-up period was 70 months. The mean values for disease-free survival and overall survival were 109 and 125 months for long-term survivors, compared to 3 and 21 months for short-term survivors, respectively. Caveolin-1 expression was localized to the cell membrane in 24/76 (32%) specimens and was detected in the cytoplasm in 52/76 (68%) cases. Both patterns were more often detected in metastases, when compared with primary tumors. In addition, membrane immunoreactivity was more often seen in tumor of short-term survivors. These differences did not reach statistical significance (P > 0.05). Combined membrane and cytoplasmic immunoreactivity was seen in 17/20 (85%) nonneoplastic lesions. Despite its role in tyrosine-kinase-mediated signal transduction in vitro studies, caveolin-1 expression in carcinomas showed no association with the protein expression of c-erbB-2 and epidermal growth factor receptor, evaluated in a previous study of this patient cohort.
This study provides the first in vivo evidence of caveolin-1 membrane expression in human malignancies. Caveolin-1 is often expressed in advanced-stage ovarian carcinoma, but does not appear to be a powerful predictor of disease outcome in these tumors. The reduced expression level in carcinomas compared to nonneoplastic epithelium may point to a role for caveolin-1 as a tumor suppressor gene.
本研究旨在分析小窝蛋白-1(小窝的蛋白质成分)的表达与晚期卵巢癌疾病转归之间的相关性。
采用免疫组织化学方法对76例原发性卵巢癌及45例诊断为晚期卵巢癌(国际妇产科联盟分期III-IV期)患者的转移病灶切片进行小窝蛋白-1表达评估。根据疾病转归将患者分为长期存活者和短期存活者。另外对20例非肿瘤性输卵管和卵巢进行了研究。
平均随访期为70个月。长期存活者的无病生存期和总生存期的平均值分别为109个月和125个月,而短期存活者分别为3个月和21个月。小窝蛋白-1表达在24/76(32%)的标本中定位于细胞膜,在52/76(68%)的病例中在细胞质中检测到。与原发性肿瘤相比,这两种模式在转移灶中更常被检测到。此外,膜免疫反应性在短期存活者的肿瘤中更常见。这些差异未达到统计学意义(P>0.05)。在17/20(85%)的非肿瘤性病变中可见膜和细胞质联合免疫反应性。尽管在体外研究中其在酪氨酸激酶介导的信号转导中发挥作用,但在该患者队列的先前研究中评估发现,癌组织中小窝蛋白-1的表达与c-erbB-2和表皮生长因子受体的蛋白表达无关联。
本研究提供了小窝蛋白-1在人类恶性肿瘤中膜表达的首个体内证据。小窝蛋白-1在晚期卵巢癌中常表达,但似乎不是这些肿瘤疾病转归的有力预测指标。与非肿瘤性上皮相比,癌组织中表达水平降低可能表明小窝蛋白-1作为肿瘤抑制基因发挥作用。