Frequent Activating Mutations of PIK3CA in Ovarian Clear Cell Carcinoma

• Published in: The American journal of pathology Vol. 174; no. 5; pp. 1597 - 1601
• Main Authors: Kuo, Kuan-Ting, Mao, Tsui-Lien, Jones, Siân, Veras, Emanuela, Ayhan, Ayse, Wang, Tian-Li, Glas, Ruth, Slamon, Dennis, Velculescu, Victor E, Kuman, Robert J, Shih, Ie-Ming
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.05.2009; ASIP; American Society for Investigative Pathology
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Clear Cell - pathology; Adenocarcinoma, Mucinous - genetics; Adenocarcinoma, Mucinous - metabolism; Adenocarcinoma, Mucinous - pathology; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - metabolism; Carcinoma, Endometrioid - pathology; Class I Phosphatidylinositol 3-Kinases; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - pathology; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunoenzyme Techniques; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mutation - genetics; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Polymorphism, Single Nucleotide - genetics; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Short Communications; Tumors; Ovary carcinoma; Enzyme; Transferases; Ovary cancer; Malignant tumor; Female genital diseases; 1-Phosphatidylinositol 3-kinase; Ovarian diseases; Anatomic pathology; Clear cell carcinoma; Frequency; Genetics; Mutation; Cancer
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2009.081000

Ovarian clear cell carcinoma (CCC) is one of the most malignant types of ovarian carcinomas, particularly at advanced stages. Unlike the more common type of ovarian cancer, high-grade serous carcinoma, ovarian CCC is often resistant to platinum-based chemotherapy, and therefore an effective treatment for this tumor type at advanced stages is urgently needed. In this study, we analyzed 97 ovarian CCCs for sequence mutations in KRAS , BRAF , PIK3CA , TP53 , PTEN , and CTNNB1 as these mutations frequently occur in other major types of ovarian carcinomas. The samples included 18 CCCs for which affinity-purified tumor cells from fresh specimens were available, 69 microdissected tumors from paraffin tissues, and 10 tumor cell lines. Sequence mutations of PIK3CA , TP53 , KRAS , PTEN, CTNNB1 , and BRAF occurred in 33%, 15%, 7%, 5%, 3%, and 1% of CCC cases, respectively. Sequence analysis of PIK3CA in 28 affinity-purified CCCs and CCC cell lines showed a mutation frequency of 46%. Samples with PIK3CA mutations showed intense phosphorylated AKT immunoreactivity. These findings demonstrate that ovarian CCCs have a high frequency of activating PIK3CA mutations. We therefore suggest that the use of PIK3CA-targeting drugs may offer a more effective therapeutic approach compared with current chemotherapeutic agents for patients with advanced-stage and recurrent CCC.