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. Materials and 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.

[1]  S. Ishikawa,et al.  Genome-wide single-nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in the PI3-kinase pathway , 2010, Oncogene.

[2]  H. Aburatani,et al.  The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas , 2009, British Journal of Cancer.

[3]  R. Zaino,et al.  FIGO Staging of Endometrial Adenocarcinoma: A Critical Review and Proposal , 2009, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[4]  K. Shokat,et al.  PIK3CA cooperates with other phosphatidylinositol 3'-kinase pathway mutations to effect oncogenic transformation. , 2008, Cancer research.

[5]  Joshua M. Korn,et al.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2008, Nature.

[6]  Ian G. Campbell,et al.  High-Resolution Single Nucleotide Polymorphism Array Analysis of Epithelial Ovarian Cancer Reveals Numerous Microdeletions and Amplifications , 2007, Clinical Cancer Research.

[7]  Y. Taketani,et al.  Combined phospho-Akt and PTEN expressions associated with post-treatment hysterectomy after conservative progestin therapy in complex atypical hyperplasia and stage Ia, G1 adenocarcinoma of the endometrium. , 2007, Cancer letters.

[8]  Frank McCormick,et al.  High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. , 2005, Cancer research.

[9]  Hiroyuki Aburatani,et al.  Allelic dosage analysis with genotyping microarrays. , 2005, Biochemical and biophysical research communications.

[10]  P. V. van Diest,et al.  The molecular genetics and morphometry‐based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system , 2005, Cancer.

[11]  X. Matías-Guiu,et al.  Synchronous endometrioid carcinomas of the uterine corpus and ovary: alterations in the beta-catenin (CTNNB1) pathway are associated with independent primary tumors and favorable prognosis. , 2005, Human pathology.

[12]  Y. Oda,et al.  Frequent microsatellite instability in synchronous ovarian and endometrial adenocarcinoma and its usefulness for differential diagnosis. , 2004, Human pathology.

[13]  T. Rollason.  Blaustein’s Pathology of the Female Genital Tract , 2003, Springer New York.

[14]  S. P. Fodor,et al.  Large-scale genotyping of complex DNA , 2003, Nature Biotechnology.

[15]  J. Torhorst,et al.  PTEN as a Molecular Marker to Distinguish Metastatic From Primary Synchronous Endometrioid Carcinomas of the Ovary and Uterus , 2003, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[16]  Y. Taketani,et al.  PTEN mutation located only outside exons 5, 6, and 7 is an independent predictor of favorable survival in endometrial carcinomas. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  K. Shroyer,et al.  Application of clonal analysis. Differential diagnosis for synchronous primary ovarian and endometrial cancers and metastatic cancer. , 1996, American journal of clinical pathology.

[18]  M. Pieretti,et al.  Loss of heterozygosity and genomic instability in synchronous endometrioid tumors of the ovary and endometrium , 1995, Cancer.

[19]  T. Frank,et al.  Synchronous dual primary ovarian and endometrial carcinomas , 1993, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[20]  A. Ayhan,et al.  Synchronous primary malignancies of the female genital tract. , 1992, European journal of obstetrics, gynecology, and reproductive biology.

[21]  J. Wharton,et al.  Endometrioid carcinoma of the ovary: Retrospective review of 145 cases , 1991 .

[22]  B. Piura,et al.  Synchronous carcinomas of endometrium and ovary , 1989, Gynecologic oncology.

[23]  J. Berek,et al.  Synchronous primary neoplasms of the female reproductive tract. , 1989, Gynecologic oncology.

[24]  R. Scully,et al.  The development of malignancy in endometriosis. , 1966, Clinical obstetrics and gynecology.

[25]  T. Ulbright,et al.  Metastatic and independent cancers of the endometrium and ovary: a clinicopathologic study of 34 cases. , 1985, Human pathology.

[26]  B. Vasilev,et al.  [Metastatic tumors of the ovary]. , 1971, Akusherstvo i ginekologiia.