Diebold J, Deisenhofer I, Baretton G B, Blasenbreu S, Suchy B, Schneiderbanger K, Meier W, Haas C J, Löhrs U
Institute of Pathology, Ludwig-Maximilians-Universität, Munich, Germany.
Lab Invest. 1996 Oct;75(4):473-85.
The cytogenetic and molecular genetic changes in serous tumors of low malignant potential (LMP) of the ovary have not been well characterized so far. Therefore, we analyzed 20 serous tumors of LMP, 10 invasive serous ovarian carcinomas, and 7 benign serous cystadenomas by nonisotopic in situ hybridization (seven different centromere-specific probes) as well as by flow and image DNA cytometry and compared the data with results of p53 and Ki67 immunohistochemistry, MYC DNA PCR analysis and with the clinical follow-up. All but two tumors of LMP were DNA cytometrically diploid; 9 of 10 invasive carcinomas proved to be DNA nondiploid (p < 0.0001). Nonisotopic in situ hybridization revealed a mean number of 1.5 chromosomal aberrations in tumors of LMP, which differed statistically significantly from cystadenomas (mean, 0.4) and from invasive carcinomas (mean, 3.4) (rho < 0.01). The main changes in tumors of LMP were +6 (7 of 18 cases) and +7 (6 of 19) followed by -3 (5 of 20), -1 (4 of 17) and +X (3 of 20). In the group of invasive carcinomas, the number of cases with signal gains for chromosomes 6 (5 of 8), 7 (7 of 10) and X (4 of 10) and signal loss for chromosome 1 (4 of 9) was even larger. In addition, statistically significantly more cases showed gain of 8 (5 of 10) and loss of 17 (5 of 10) (p < 0.05). Proliferative activity (Ki67 index) was positively correlated with the number of chromosomal aberrations (p < 0.05). There was no association between changes in the centromere signal number of chromosomes 8 and 17 and MYC DNA amplification and immunohistochemical p53 accumulation, respectively. Clinical follow-up showed prognostic differences between tumors of LMP and invasive carcinomas as expected (rho < 0.001) but did not reveal differences within the group of tumors of LMP with regard to the number or type of the chromosomal abnormalities detected. In conclusion, the patterns of chromosomal gains and losses in serous tumors of LMP and invasive serous carcinomas of the ovary do not seem random and suggest a close relation between these neoplasms compatible with sequential stages in a multistep model of ovarian carcinogenesis.
卵巢低恶性潜能（LMP）浆液性肿瘤的细胞遗传学和分子遗传学变化迄今尚未得到充分表征。因此，我们通过非同位素原位杂交（七种不同的着丝粒特异性探针）以及流式和图像DNA细胞术分析了20例LMP浆液性肿瘤、10例浸润性浆液性卵巢癌和7例良性浆液性囊腺瘤，并将数据与p53和Ki67免疫组化、MYC DNA PCR分析结果以及临床随访结果进行了比较。除两例LMP肿瘤外，所有肿瘤在DNA细胞术上均为二倍体；10例浸润性癌中有9例被证明为DNA非二倍体（p<0.0001）。非同位素原位杂交显示，LMP肿瘤中平均有1.5个染色体畸变，这与囊腺瘤（平均0.4个）和浸润性癌（平均3.4个）在统计学上有显著差异（rho<0.01）。LMP肿瘤的主要变化为+6（18例中的7例）和+7（19例中的6例），其次为-3（20例中的5例）、-1（17例中的4例）和+X（20例中的3例）。在浸润性癌组中，染色体6（8例中的5例）、7（10例中的7例）和X（10例中的4例）信号增加以及染色体1（9例中的4例）信号缺失的病例数甚至更多。此外，在统计学上有显著更多的病例显示8号染色体增加（10例中的5例）和17号染色体缺失（10例中的5例）（p<0.05）。增殖活性（Ki67指数）与染色体畸变数量呈正相关（p<0.05）。8号和17号染色体着丝粒信号数量的变化分别与MYC DNA扩增和免疫组化p53积累之间没有关联。临床随访显示，LMP肿瘤和浸润性癌之间存在预期的预后差异（rho<0.001），但在LMP肿瘤组中，就检测到的染色体异常数量或类型而言，未发现差异。总之，卵巢LMP浆液性肿瘤和浸润性浆液性癌中的染色体增减模式似乎并非随机，表明这些肿瘤之间存在密切关系，符合卵巢癌发生多步骤模型中的连续阶段。
