Genome-wide single nucleotide polymorphism arrays as a diagnostic tool in patients with synchronous endometrial and ovarian cancer.
OBJECTIVE
Synchronous carcinomas in the endometrium and ovaries can be a single primary tumor with metastasis (SPM) or dual primary tumors (DP). Although the prognosis of DP without any metastases is significantly better than that of SPM, pathological diagnosis is difficult in tumors with similar histological features.


METHODS
In 10 tumors from 5 patients with synchronous endometrial and ovarian carcinomas, 250K single nucleotide polymorphism arrays were performed. The patients were genetically diagnosed according to the pattern of copy number alterations (CNAs), in addition to microsatellite status and mutational analysis of PIK3CA, PTEN, K-Ras, and CTNNB1.


RESULTS
Of the 5 patients, 3 exhibited identical CNA patterns, including type, loci, and degree of each alteration in the endometrial and ovarian carcinomas. The other 2 exhibited CNAs only in either endometrial or ovarian carcinoma. All 5 tumors had 1 or more genetic mutations in the genes examined. One patient exhibited mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other 4 exhibited concordant mutations. Overall, 4 of the 5 patients were genetically diagnosed with SPM, and the remaining 1 with DP. The pathological diagnosis was not in agreement with the genetic diagnosis in 4 of the 5 patients.


CONCLUSIONS
Genome-wide genotyping diagnosis may represent a useful approach for distinguishing between SPM and DP in synchronous endometrial and ovarian carcinomas.
Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Yuji
Y
Ikeda
Katsutoshi
K
Oda
Shunsuke
S
Nakagawa
Satsuki
S
Murayama-Hosokawa
Shogo
S
Yamamoto
Shumpei
S
Ishikawa
Linghua
L
Wang
Yutaka
Y
Takazawa
Daichi
D
Maeda
Osamu
O
Wada-Hiraike
Kei
K
Kawana
Masashi
M
Fukayama
Hiroyuki
H
Aburatani
Tetsu
T
Yano
Shiro
S
Kozuma
Yuji
Y
Taketani
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D056915:DNA Copy Number Variations; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D051176:beta Catenin / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins