Sullivan Mackenzie W, Chui M Herman, Selenica Pier, Long Roche Kara, Sonoda Yukio, Grisham Rachel N, Kyi Chrisann, Momeni-Boroujeni Amir, Abu-Rustum Nadeem R, Weigelt Britta, O'Cearbhaill Roisin E
Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Gynecol Oncol. 2025 Apr;195:144-148. doi: 10.1016/j.ygyno.2025.03.021. Epub 2025 Mar 19.
We describe a tertiary referral center's experience with anaplastic ovarian carcinoma and characterize the genetic landscape of these rare tumors.
Anaplastic ovarian carcinomas were retrospectively identified from institutional databases from 2013 to 2023. Clinical data and survival outcomes were abstracted from the electronic medical record. Molecular data were obtained from clinical tumor-normal panel sequencing.
Thirteen tumors were identified; 12 (92 %) were associated with or arose from a mucinous carcinoma, and 6 (46 %) were found in a mural nodule. Median age at diagnosis was 39 years (range, 19-77); 6 patients had stage I disease (3 stage IA), 1 had stage II, 5 had stage III, and 1 had stage IV. All patients underwent surgery. First-line postoperative therapy included carboplatin-paclitaxel doublet (n = 8), a 5-fluorouracil-oxaliplatin-based regimen (FOLFOX, n = 1; XELOX, n = 2), and ifosfamide/paclitaxel (n = 1). Two patients did not receive adjuvant chemotherapy for early-stage disease. Six patients had progression or recurrence; 5 had platinum-refractory disease and 1 had an initial progression-free interval of 6.8 months. For the 7 patients without recurrence, median follow-up was 79.7 months. Median overall survival for all patients was 28.1 months (range, 7.8-139.2). Five patients died of their disease. Ten patients had clinical panel sequencing, revealing recurrent somatic KRAS G12D/V hotspot mutations (8 of 10, 80 %) and genetic alterations affecting cell cycle-related genes, including TP53 (6 of 10, 60 %) and CDKN2A (6 of 10, 60 %).
Anaplastic ovarian carcinoma is characterized by KRAS, TP53, and CDKN2A alterations. Novel treatment approaches are needed due to the high rate of platinum-refractory disease.
我们描述了一家三级转诊中心治疗间变性卵巢癌的经验,并对这些罕见肿瘤的基因图谱进行了特征分析。
从2013年至2023年的机构数据库中回顾性识别间变性卵巢癌。从电子病历中提取临床数据和生存结果。分子数据通过临床肿瘤-正常组织全外显子测序获得。
共识别出13例肿瘤;12例(92%)与黏液性癌相关或由黏液性癌发展而来,6例(46%)位于壁层结节。诊断时的中位年龄为39岁(范围19 - 77岁);6例患者为Ⅰ期疾病(3例ⅠA期),1例为Ⅱ期,5例为Ⅲ期,1例为Ⅳ期。所有患者均接受了手术。一线术后治疗包括卡铂-紫杉醇双联方案(n = 8)、基于5-氟尿嘧啶-奥沙利铂的方案(FOLFOX,n = 1;XELOX,n = 2)以及异环磷酰胺/紫杉醇(n = 1)。2例早期疾病患者未接受辅助化疗。6例患者出现进展或复发;5例为铂类难治性疾病,1例初始无进展生存期为6.8个月。对于7例未复发的患者,中位随访时间为79.7个月。所有患者的中位总生存期为28.1个月(范围7.8 - 139.2个月)。5例患者死于该疾病。10例患者进行了临床全外显子测序,发现复发性体细胞KRAS G12D/V热点突变(10例中的8例,80%)以及影响细胞周期相关基因的基因改变,包括TP53(10例中的6例,60%)和CDKN2A(10例中的6例,60%)。
间变性卵巢癌的特征是KRAS、TP53和CDKN2A改变。由于铂类难治性疾病的高发生率,需要新的治疗方法。