Kowalski L D, Kanbour A I, Price F V, Finkelstein S D, Christopherson W A, Seski J C, Naus G J, Burnham J A, Kanbour-Shakir A, Edwards R P
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh Health Sciences Center, Magee-Womens Hospital, Pennsylvania, USA.
Cancer. 1997 Apr 15;79(8):1587-94.
Extraovarian müllerian adenocarcinoma (EOM) resembles primary ovarian carcinoma (POC) both histologically and clinically, yet little is known regarding the molecular genetic characteristics of this entity. The objective of this study was to compare the expression of three molecular markers of tumor behavior in EOMs and POCs.
Forty-four patients meeting strict criteria for EOM were identified and matched to POC controls for age, stage, tumor histology and grade, cytoreductive surgery, and survival. Immunohistochemistry was used to determine overexpression of p53 and HER-2/neu. DNA content was evaluated by flow cytometry. Direct DNA sequencing of exons 5-8 of the p53 gene was performed in nine EOM tumors. Statistical comparisons were made using chi-square, Kaplan-Meier, and Mantel-Cox log rank methods.
Overexpression of HER-2/neu was demonstrated in 59% (26 of 44) of the EOM group versus 36% overexpression (16 of 44) in the POC controls (P = 0.05). Overexpression of p53 was noted in 48% of the EOM cases, similar to the 59% incidence observed in the control group (P = 0.29). Missense mutations were found in 9 of 9 EOM tumors showing strong p53 nuclear immunostaining. No significant difference in the incidence of aneuploidy was observed when EOM cases were compared with POC controls (65% vs. 63%). High tumor grade was strongly associated with HER-2/neu overexpression in the EOM group (P = 0.002). None of the parameters studied were predictive of prognosis within the EOM and POC groups.
Although overexpression of p53 protein, p53 gene mutations, and abnormal DNA content were similar between EOMs and POCs, EOMs demonstrated almost twice the rate of HER-2/neu overexpression. This result suggests that distinct genetic events may be responsible for malignant transformation in EOMs versus POCs.
卵巢外苗勒管腺癌（EOM）在组织学和临床上与原发性卵巢癌（POC）相似，但对于该实体的分子遗传学特征知之甚少。本研究的目的是比较EOM和POC中三种肿瘤行为分子标志物的表达情况。
确定了44例符合EOM严格标准的患者，并将其与POC对照在年龄、分期、肿瘤组织学和分级、肿瘤细胞减灭术及生存率方面进行匹配。采用免疫组织化学法确定p53和HER-2/neu的过表达情况。通过流式细胞术评估DNA含量。对9例EOM肿瘤进行p53基因第5至8外显子的直接DNA测序。使用卡方检验、Kaplan-Meier法和Mantel-Cox对数秩检验进行统计学比较。
EOM组中59%（44例中的26例）显示HER-2/neu过表达，而POC对照组中过表达率为36%（44例中的16例）（P = 0.05）。48%的EOM病例中观察到p53过表达，与对照组中59%的发生率相似（P = 0.29）。在9例显示p53强核免疫染色的EOM肿瘤中，有9例发现错义突变。将EOM病例与POC对照进行比较时，非整倍体发生率无显著差异（65%对63%）。在EOM组中，高肿瘤分级与HER-2/neu过表达密切相关（P = 0.002）。所研究的参数均不能预测EOM和POC组的预后。
尽管EOM和POC之间p53蛋白过表达、p53基因突变及DNA含量异常情况相似，但EOM中HER-2/neu过表达率几乎是POC的两倍。这一结果表明，EOM与POC的恶性转化可能由不同的基因事件所致。
