Improved survival in women with BRCA-associated ovarian carcinoma
Improved survival in women with BRCA-associated ovarian carcinoma
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DOI：
10.1002/cncr.11310
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发表时间：
2003-05-01
期刊：
影响因子：
6.2
通讯作者：
Karlan, BY
中科院分区：
文献类型：
--
作者：
Cass, I;Baldwin, RL;Karlan, BY
背景：本研究旨在确定患有遗传性卵巢癌的德系犹太女性的临床特征、治疗反应以及p53过度表达的频率。
方法：对71名患有上皮性卵巢癌（EOC）的犹太女性使用单链构象多态性分析、异源双链分析和蛋白质截短试验检测三种BRCA founder突变。回顾性分析临床和组织病理学数据。对32名患者进行体外化疗耐药性分析。使用免疫组化检测p53过度表达来研究p53突变。
结果：71名患有EOC的犹太患者中有34名（48%）存在生殖系BRCA突变（BRCA杂合子），包括22例BRCA1突变和12例BRCA2突变。与无突变的患有EOC的犹太患者（散发性癌）相比，BRCA杂合子更年轻（分别为50岁和59岁；P = 0.01）。BRCA1杂合子比BRCA2杂合子更年轻（分别为48岁和57岁；P = 0.01）。组织病理学肿瘤特征相似；然而，低恶性潜能肿瘤仅见于散发性癌女性。两组的手术细胞减灭率相当，中位随访时间相似（72个月）。与散发性疾病患者相比，BRCA杂合子对初始治疗的反应率更高（P = 0.01）。体外化疗耐药性正确预测了BRCA杂合子对铂类化疗的肿瘤反应（P = 0.0096）。与晚期散发性癌患者相比，患有晚期疾病的BRCA杂合子生存期更长（分别为91个月和54个月，P = 0.046），无病间期更长（分别为49个月和19个月；P = 0.16）。p53过度表达在BRCA杂合子中很常见（80%）。
结论：与BRCA2杂合子和散发性卵巢癌女性相比，BRCA1杂合子患EOC的年龄更小。与散发性疾病女性相比，BRCA杂合子对铂类化疗反应更好，这可能有助于改善其预后。《癌症》2003年；97:2187 - 2195。（C）2003美国癌症协会。DOI 10.1002/cncr.11310
BACKGROUND. The objective of this study was to determine the clinical characteristics, treatment response, and frequency of p53 overexpression in Ashkenazi Jewish women with hereditary ovarian carcinoma.METHODS. Seventy-one Jewish women with epithelial ovarian carcinoma (EOC) were tested for the three BRCA founder mutations using single-strand conformation polymorphism analysis, heteroduplex analysis, and protein truncation testing. Clinical and histopathologic data were reviewed retrospectively. In vitro chemoresistance was analyzed in 32 patients. Mutations of p53 were studied using immunohistochemical detection of p53 overexpression.RESULTS. Thirty-four of 71 Jewish patients with EOC (48%) had germline BRCA mutations (BRCA heterozygotes), including 22 BRCA1 mutations and 12 BRCA2 mutations. BRCA heterozygotes were younger compared with Jewish patients who had EOC without mutations (sporadic carcinoma; 50 years vs'. 59 years, respectively; P = 0.01). BRCA1 heterozygotes were younger compared with BRCA2 heterozygotes (48 years vs. 57 years, respectively; P = 0.01). Histopathologic tumor features were similar; however, tumors with low malignant potential were seen only in women with sporadic carcinoma. Both groups had equivalent rates of surgical cytoreduction and similar median follow-up (72 months). BRCA heterozygotes had higher response rates to primary therapy compared with patients who had sporadic disease (P = 0.01). In vitro chemoresistance predicted tumor response to platinum chemotherapy correctly in BRCA heterozygotes (P = 0.0096). BRCA heterozygotes with advance-stage disease had improved survival compared with patients who had advanced stage sporadic carcinoma (91 months vs. 54 months, respectively, P = 0.046) and had a longer disease free interval (49 months vs. 19 months, respectively; P = 0.16). p53 overexpression was common in BRCA heterozygotes (80%).CONCLUSIONS. BRCA1 heterozygotes developed EOC at a younger age compared with BRCA2 heterozygotes and women who had sporadic ovarian carcinoma. BRCA heterozygotes had a better response to platinum chemotherapy compared with women who had sporadic disease, which may have contributed to their improved prognosis. Cancer 2003;97:2187-95. (C) 2003 American Cancer Society. DOI 10.1002/cncr.11310.