Abstract

<div>AbstractPurpose:<p>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.</p>Experimental Design:<p>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 (<i>n</i> = 333), mucinous borderline ovarian tumors (MBOT, <i>n</i> = 151), and upper GI (<i>n</i> = 65) and lower GI tumors (<i>n</i> = 55).</p>Results:<p>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, <i>P</i> = 0.042]. Increased expression of <i>THBS2</i> and <i>TAGLN</i> was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, <i>P</i> = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, <i>P</i> = 0.043), respectively. <i>ERBB2</i> (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%).</p>Conclusions:<p>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 <i>THBS2</i> and <i>TAGLN</i> 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.</p></div>

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