Lu K H, Bell D A, Welch W R, Berkowitz R S, Mok S C
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Res. 1998 Jun 1;58(11):2328-30.
Borderline ovarian tumors (BOTs), or ovarian tumors of low malignant potential, represent a distinct category of epithelial ovarian neoplasms that have a clinically more favorable outcome than invasive epithelial ovarian cancer. Histologically, BOTs and invasive ovarian carcinomas both show cellular proliferation and pleomorphism, but unlike invasive ovarian carcinomas, BOTs lack stromal invasion. Although serous BOTs are frequently confined to a single ovary at the time of diagnosis, bilateral or extra-ovarian spread occurs in 30-40% of cases. The purpose of this study is to determine whether bilateral or extraovarian serous borderline lesions are metastatic sites from the original tumor, or represent separate primary tumors. DNA specimens from multiple tumor sites and normal tissue controls were obtained in eight women with bilateral or extra-ovarian serous borderline tumors. The pattern of loss of heterozygosity at the androgen receptor locus on the X chromosome was evaluated in the multiple tumor sites. In addition, the pattern of X-chromosome inactivation was determined using HpaII restriction endonuclease digestion, followed by PCR amplification of the androgen receptor locus. Multifocality was determined when alternate patterns of X-chromosome inactivation occurred. In two of the eight patients, the left and right ovarian tumor sites had different androgen receptor alleles inactivated, indicating that the bilateral tumors derived independently. In a third patient, the X inactivation pattern in the left ovarian tumor differed from the two peritoneal implants, suggesting that the implants were separate primary tumors, and not metastatic, from the left ovarian tumor. The remaining five patients had the same pattern of loss of heterozygosity and X inactivation in the tumor sites studied. These results suggest that bilateral and advanced stage serous BOTs may be multifocal in origin. This result is in contrast to invasive epithelial ovarian cancer, which has been shown to be unifocal in origin.
交界性卵巢肿瘤（BOTs），即低度恶性潜能卵巢肿瘤，是上皮性卵巢肿瘤中的一个独特类别，其临床预后比浸润性上皮性卵巢癌更为良好。从组织学上看，BOTs和浸润性卵巢癌均表现出细胞增殖和多形性，但与浸润性卵巢癌不同的是，BOTs缺乏间质浸润。尽管浆液性BOTs在诊断时通常局限于一侧卵巢，但30%-40%的病例会出现双侧或卵巢外播散。本研究的目的是确定双侧或卵巢外浆液性交界性病变是原发肿瘤的转移部位，还是代表独立的原发肿瘤。在8例患有双侧或卵巢外浆液性交界性肿瘤的女性中，获取了多个肿瘤部位的DNA标本以及正常组织对照。对多个肿瘤部位X染色体上雄激素受体位点的杂合性缺失模式进行了评估。此外，使用HpaII限制性内切酶消化，随后对雄激素受体位点进行PCR扩增，以确定X染色体失活模式。当出现交替的X染色体失活模式时，确定为多灶性。在8例患者中的2例中，左侧和右侧卵巢肿瘤部位有不同的雄激素受体等位基因失活，表明双侧肿瘤是独立发生的。在第3例患者中，左侧卵巢肿瘤的X失活模式与两个腹膜种植灶不同，提示这些种植灶是独立的原发肿瘤，而非来自左侧卵巢肿瘤的转移灶。其余5例患者在所研究的肿瘤部位具有相同的杂合性缺失和X失活模式。这些结果表明，双侧和晚期浆液性BOTs可能起源于多灶性。这一结果与浸润性上皮性卵巢癌相反，后者已被证明起源于单灶性。
