Survival Following Chemotherapy in Ovarian Clear Cell Carcinoma Is Not Associated with Pathological Misclassification of Tumor Histotype.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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).

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Masataka Takenaka, Martin Köbel, Dale W Garsed, Sian Fereday, Ahwan Pandey, Dariush Etemadmoghadam, Joy Hendley, Ayako Kawabata, Daito Noguchi, Nozomu Yanaihara, Hiroyuki Takahashi, Takako Kiyokawa, Masahiro Ikegami, Hirokuni Takano, Seiji Isonishi, Kazuhiko Ochiai, Nadia Traficante, Sreeja Gadipally, Timothy Semple, Dane Vassiliadis, Kausyalya Amarasinghe, Jason Li, Gisela Mir Arnau, Aikou Okamoto, Michael Friedlander, David D L Bowtell, Australian Ovarian Cancer Study Group
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 25 Issue 13 Pg. 3962-3973 (07 01 2019) ISSN: 1557-3265 [Electronic] United States
• PMID: 30967419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Biomarkers

Topics

• Adenocarcinoma, Clear Cell (drug therapy, etiology, mortality, pathology)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers
• Diagnostic Errors
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Mutation
• Neoplasm Grading
• Neoplasm Staging
• Ovarian Neoplasms (drug therapy, etiology, mortality, pathology)
• Prognosis
• Treatment Outcome