School of Clinical Medicine, Faculty of Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.
Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia.
Clin Cancer Res. 2022 Dec 15;28(24):5383-5395. doi: 10.1158/1078-0432.CCR-22-1206.
Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.
Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).
Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).
An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
晚期黏液性卵巢癌（MOC）对化疗反应差，预后差，缺乏辅助治疗的生物标志物。由于表型相似，区分原发性 MOC 与胃肠道（GI）转移到卵巢也具有挑战性。分析临床病理和基因表达数据以确定预后和诊断特征。
发现分析选择了 19 个具有预后/诊断潜力的基因。通过卵巢肿瘤组织分析联盟和包括 604 名 MOC（n=333）、黏液性交界性卵巢肿瘤（MBOT，n=151）、上 GI（n=65）和下 GI 肿瘤（n=55）的 GI 癌症生物库进行验证。
与膨胀型相比，I 期 MOC 的侵袭浸润模式与诊断后 2 年内总生存期（OS）降低相关[风险比（HR），2.77；95%置信区间（CI），1.04-7.41，P=0.042]。THBS2 和 TAGLN 的表达增加与 MOC 患者的 OS 更短相关（HR，1.25；95%CI，1.04-1.51，P=0.016）和（HR，1.21；95%CI，1.01-1.45，P=0.043）。在 243 例 MOC 中有 64 例（26%）存在 ERBB2（HER2）扩增或高 mRNA 表达，但只有 243 例中有 8 例（3%）为浸润性（4/39，10%）或 III/IV 期（4/31，13%）。
浸润性生长模式预示着诊断后 2 年内预后不良，可能有助于选择 I 期患者进行辅助治疗。MOC 中 THBS2 和 TAGLN 的高表达预示着不良预后，并且在上皮浸润型中上调，这值得进一步研究。应在部分患者中研究抗 HER2 治疗。MOC 样本与上 GI 聚集，但区分这些实体的标志物仍不清楚，这表明存在相似的潜在生物学和共同的治疗策略。
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