Kalli Kimberly R, Oberg Ann L, Keeney Gary L, Christianson Teresa J H, Low Philip S, Knutson Keith L, Hartmann Lynn C
Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Gynecol Oncol. 2008 Mar;108(3):619-26. doi: 10.1016/j.ygyno.2007.11.020. Epub 2008 Jan 28.
Folate receptor alpha (FRalpha) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FRalpha expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.
FRalpha expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FRalpha staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.
FRalpha expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FRalpha status detected at diagnosis. Metastatic foci were similar to primary tumors in FRalpha staining. FRalpha status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.
FRalpha expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FRalpha expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer.
叶酸受体α(FRα)是一种在卵巢癌和其他几种上皮性恶性肿瘤中过度表达的叶酸结合蛋白,可作为成像和治疗策略的靶点。本研究的目的是完善历史数据,这些数据缺乏关于FRα在罕见组织学亚型、原发性疾病与转移灶以及复发性疾病中表达的具体信息。
通过免疫组织化学分析了186例原发性和27例复发性卵巢肿瘤中的FRα表达,其中包括24对在诊断时和二次减瘤手术时从同一患者获取的样本。对于186例原发性肿瘤中的20例,同时也分析了其转移灶。根据疾病形态、分期、分级、减瘤状态以及从诊断到复发和死亡的时间对FRα染色进行分析。
186例原发性卵巢肿瘤中有134例(72%)和27例复发性卵巢肿瘤中有22例(81.5%)出现FRα表达。在24对匹配样本中的21对(87.5%)中,复发性肿瘤反映了诊断时检测到的FRα状态。转移灶在FRα染色方面与原发性肿瘤相似。在单变量或多变量分析中,FRα状态与复发时间或总生存期均无关联。
FRα表达频繁出现,尤其是在最易复发的常见高级别、高分期浆液性肿瘤中。本研究的新发现表明,FRα表达在转移灶和复发性肿瘤中得以维持,这表明新型叶酸靶向治疗可能对大多数新诊断或复发性卵巢癌女性患者具有前景。