High frequency of POLE mutations in synchronous endometrial and ovarian carcinoma

Synchronous endometrial and ovarian carcinomas) represent 5% to 10% of endometrial or ovarian carcinomas. We assessed genetic alterations (in PTEN, CTNNB1, POLE, etc) and evaluated correlations with patient outcomes to determine the utility of clonality analyses for differentiating between metastase...

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Bibliographic Details
Published in:Human pathology 2019-03, Vol.85, p.92-100
Main Authors: Ishikawa, Masako, Nakayama, Kentaro, Nakamura, Kohei, Ono, Ruriko, Yamashita, Hitomi, Ishibashi, Tomoka, Minamoto, Toshiko, Iida, Kouji, Razia, Sultana, Ishikawa, Noriyoshi, Kyo, Satoru
Format: Article
Language:English
Subjects:
Age
Checkpoint blockade immune therapies
Chemotherapy
Clonal relationship
Deoxyribonucleic acid
DNA
Endometrial cancer
Gene sequencing
Medical prognosis
Metastasis
Mutation
Ovarian cancer
Patients
POLE
Synchronous ovarian and endometrial carcinoma
Tumor mutation burden
Tumors
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Summary:Synchronous endometrial and ovarian carcinomas) represent 5% to 10% of endometrial or ovarian carcinomas. We assessed genetic alterations (in PTEN, CTNNB1, POLE, etc) and evaluated correlations with patient outcomes to determine the utility of clonality analyses for differentiating between metastases and concurrent primary tumors and for determining whether genetic alterations in synchronous tumors are predictive of biological behavior. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tissues and frozen tissues from patients with synchronous endometrial and ovarian carcinomas. Samples were obtained from the Department of Obstetrics and Gynecology at the Shimane University School of Medicine between 2003 and 2017. Sanger sequencing was used to analyze the mutational status of the coding exons in TP53, PTEN, POLE, PIK3CA, KRAS, and CTNNB1 using previously published primers. All patients lived, and 3 had disease recurrence. The frequencies of somatic mutations in TP53, PTEN, CTNNB1, KRAS, and POLE were 3 (37.5%), 2 (25.0%), 3 (37.5%), 0 (0.0%), and 5 (62.5%) of 8 cases in ovarian tumors and 3 (37.5%), 2 (25.0%), 3 (37.5%), 1 (12.5%), and 5 (62.5%) of 8 cases in endometrial tumors, respectively. The frequencies of POLE and CTNNB1 mutations were higher than those in previous reports. A clonal relationship was determined by genomic analyses in 3 of 6 cases that were initially diagnosed as primary independent tumors. We confirmed that these 3 cases were indicated metastatic tumors because the lesion of mutation was the same. This information, provided by the sequencing-based strategy, could be useful for hypothesizing a patient's prognosis and deciding on treatment. •Molecular analyses can provide useful diagnostic and prognostic information for SEOs.•Clinical sequencing will be an important strategy for diagnosis and treatment decisions for SEOs.•POLE mutations in both the ovarian and endometrial tumor of a patient were detected in 62.5% of the cases.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2018.11.001