PIK3CA hotspot mutations and cyclooxygenase-2 expression in ovarian clear cell carcinomas: a close association with stromal features.

Abstract

Ovarian clear cell carcinomas (CCCs) have 2 distinct stromas: a hyalinized/mucoid stroma and a plasma cell-rich inflammatory stroma. Clinically, CCC is the most common ovarian cancer associated with thromboembolism. Recent studies suggested a potential role of PIK3CA mutation in the cyclooxygenase (COX) pathway, which mediates inflammation or hemostasis. In the present study, 54 ovarian CCCs and 3 CCC cell lines were analyzed for PIK3CA hotspot mutation and COX-2 expression with special reference to stromal features. Among the 54 CCCs, 20 (37.0%) and 8 (14.8%) were classified as CCCs with a hyalinized/mucoid stroma and an inflammatory stroma, respectively. PIK3CA mutation was identified in 11 (55%) of the 20 CCCs with a hyalinized/mucoid stroma, but not in any of the 8 CCCs with an inflammatory stroma. In contrast, COX-2 expression was frequent in CCCs with an inflammatory stroma (1/20 [5%] versus 7/8 [87.5%], respectively). Such a relationship between the PIK3CA mutation, COX-2 expression, and stromal features was repeated in the 3 CCC cell lines. Thromboembolism was noted in 9 (16.7%) of the 54 CCC patients, and it was more frequent in CCCs with a hyalinized/mucoid stroma (7/20 [35%]) than in those with an inflammatory stroma (0/8 [0%]). In conclusion, there is a difference in PIK3CA mutation, COX-2 expression, and paraneoplastic thromboembolism between CCCs with a different stroma. It is suggested that a different stromal feature, either hyalinized/mucoid change or inflammation, represents a different molecular genetic background or hemostatic potential in ovarian CCCs.

• Authors: Noriko Kato, Yuka Sato, Akihisa Kamataki, Masayuki Fukase, Shinya Uchigasaki, Akira Kurose
• Journal: Human pathology (Hum Pathol) Vol. 86 Pg. 32-37 (04 2019) ISSN: 1532-8392 [Electronic] United States
• PMID: 30496799 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Cyclooxygenase 2
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human

Topics

• Adenocarcinoma, Clear Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Class I Phosphatidylinositol 3-Kinases (genetics)
• Cyclooxygenase 2 (metabolism)
• DNA Mutational Analysis
• Female
• Humans
• Mutation
• Ovarian Neoplasms (genetics, metabolism, pathology)
• Ovary (metabolism, pathology)
• Stromal Cells (metabolism, pathology)