Abstract
Although ovarian clear cell carcinomas (OCCC) are commonly resistant to platinum-based chemotherapy, good clinical outcomes are observed in a subset of patients. The explanation for this is unknown but may be due to misclassification of high-grade serous ovarian cancer (HGSOC) as OCCC or mixed histology. To discover potential biomarkers of survival benefit following platinum-based chemotherapy, we ascertained a cohort of 68 Japanese and Australian patients in whom progression-free survival (PFS) and overall survival (OS) could be assessed. We performed IHC reclassification of tumors, and targeted sequencing and immunohistochemistry of known driver genes. Exome sequencing was performed in 10 patients who had either unusually long survival (N = 5) or had a very short time to progression (N = 5). The majority of mixed OCCC (N = 6, 85.7%) and a small proportion of pure OCCC (N = 3, 4.9%) were reclassified as likely HGSOC. However, the PFS and OS of patients with misclassified samples were similar to that of patients with pathologically validated OCCC. Absent HNF1B expression was significantly correlated with longer PFS and OS (P = 0.0194 and 0.0395, respectively). Mutations in ARID1A, PIK3CA, PPP2R1A, and TP53 were frequent, but did not explain length of PFS and OS. An exploratory exome analysis of patients with favorable and unfavorable outcomes did not identify novel outcome-associated driver mutations. Survival benefit following chemotherapy in OCCC was not associated with pathological misclassification of tumor histotype. HNF1B loss may help identify the subset of patients with OCCC with a more favorable outcome.
Highlights
Survival benefit following chemotherapy in Ovarian clear cell carcinoma (OCCC) was not associated with pathological misclassification of tumor histotype
To evaluate survival outcomes following platinum-based chemotherapy in patients with OCCC, we first excluded those with tumors who may have been cured by surgery alone and selected patients with residual disease following primary debulking surgery and who subsequently received adjuvant chemotherapy
In a cohort of patients with Australian and Japanese OCCC, we found that superior progression-free survival (PFS) and overall survival (OS) was not due to pathologic misclassification of high-grade serous ovarian carcinomas (HGSOC) as OCCC, or due to the presence of TP53 mutations and other driver mutations associated with HGSOC
Summary
Epithelial ovarian cancer (EOC) predominantly consists of five histologic subtypes: high-grade serous, low-grade serous, endo-Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).Ó2019 American Association for Cancer Research.metrioid, clear cell, and mucinous carcinomas, and these differ in clinicopathologic characteristics including chemo-sensitivity and molecular features as well as patient outcomes [1, 2]. Epithelial ovarian cancer (EOC) predominantly consists of five histologic subtypes: high-grade serous, low-grade serous, endo-. Metrioid, clear cell, and mucinous carcinomas, and these differ in clinicopathologic characteristics including chemo-sensitivity and molecular features as well as patient outcomes [1, 2]. Ovarian clear cell carcinoma (OCCC) is uncommon, and diagnosed in only approximately 12% of women with EOC in Western countries. OCCC is associated with a poorer prognosis, especially in advanced stage disease, compared with other EOC subtypes and is typically resistant to platinum-based therapy [2, 4, 5]. Response rates of OCCC to conventional platinum-based chemotherapy are variable and range from 11% to 56% in the first-line setting, and contrast sharply with the responses rates of >80% in the more common high-grade serous ovarian carcinomas Response rates of OCCC to conventional platinum-based chemotherapy are variable and range from 11% to 56% in the first-line setting, and contrast sharply with the responses rates of >80% in the more common high-grade serous ovarian carcinomas (HGSOC; refs. 2, 4, 5)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
