Molecular evidence for the independent origin of extra-ovarian papillary serous tumors of low malignant potential.

BACKGROUND Molecular data suggest that peritoneal tumors in women with advanced-stage ovarian papillary serous adenocarcinoma are monoclonal in origin. Whether the same is true for ovarian tumors of low malignant potential is not known. We compared peritoneal and ovarian tumors from women with advanced-stage ovarian papillary serous tumors of low malignant potential to determine whether the peritoneal tumors arose from the same clone as the ovarian tumors. METHODS We studied the clonality of 73 peritoneal and ovarian tumors from 18 women with advanced-stage ovarian papillary serous tumors of low malignant potential. Formalin-fixed, paraffin-embedded tumors and representative normal tissues were sectioned and stained with hematoxylin-eosin, representative sections from separate tumors were manually microdissected, genomic DNA was extracted from the microdissected tumors, and the polymerase chain reaction was used to amplify a CAG polymorphic site in the human androgen receptor locus on the X chromosome to determine the inactivation pattern of the X chromosome and the clonality of the tumors. RESULTS The pattern of X-chromosome inactivation could be determined from the tumors of 13 of 18 patients. Of the 13 patients, seven (54%) had nonrandom inactivation of the X chromosome, and six of the seven had different inactivation patterns in the peritoneal and ovarian tumors. Three of these patients also had different patterns of nonrandom X-chromosome inactivation in tumors from each ovary. The remaining six patients had random patterns of X-chromosome inactivation in the peritoneal and ovarian tumors. CONCLUSIONS Our data suggest that peritoneal and ovarian tumors of low malignant potential arise independently.

[1]  Aimo Ojala.  Studies on Bilirubin in Amniotic Fluid: With Special Reference to Liver Function Tests , 1971, Acta obstetricia et gynecologica Scandinavica. Supplement.

[2]  R. Scully.  Ovarian tumors. A review. , 1977, The American journal of pathology.

[3]  P. Russell.  The pathological assessment of ovarian neoplasms. I: Introduction to the common 'epithelial' tumours and analysis of benign 'epithelial' tumours. , 1979, Pathology.

[4]  Survey of clinical behavior of patients with borderline epithelial tumors of the ovary , 1981 .

[5]  H. Michael,et al.  Invasive and noninvasive implants in ovarian serous tumors of low malignant potential , 1986, Cancer.

[6]  D. Bostwick,et al.  Ovarian epithelial tumors of borderline malignancy: A clinical and pathologic study of 109 cases , 1986, Cancer.

[7]  P. Schwartz,et al.  Borderline ovarian tumors , 1988, American journal of obstetrics and gynecology.

[8]  M. Weinstock,et al.  Peritoneal implants of ovarian serous borderline tumors: Histologic features and prognosis , 1988, Cancer.

[9]  J. Wilson,et al.  Characterization and expression of a cDNA encoding the human androgen receptor. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Berkowitz,et al.  Epithelial ovarian tumors of borderline malignancy. , 1990, Gynecologic oncology.

[11]  F. Mitelman,et al.  Bilateral ovarian carcinoma: Cytogenetic evidence of unicentric origin , 1991, International journal of cancer.

[12]  W. Creasman,et al.  Epithelial Ovarian Tumors of Low Malignant Potential , 1991, Obstetrics and gynecology.

[13]  W. R. Hart,et al.  Ovarian Serous Tumors of Low Malignant Potential (Serous Borderline Tumors) The Relationship of Exophytic Surface Tumor to Peritoneal “Implants” , 1992, The American journal of surgical pathology.

[14]  R. Izumi,et al.  [Ovarian epithelial tumors of borderline malignancy]. , 1992, Rinsho byori. The Japanese journal of clinical pathology.

[15]  H. Zoghbi,et al.  Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. , 1992, American journal of human genetics.

[16]  J. Woodruff,et al.  Long-term follow-up of serous ovarian tumors of low malignant potential. , 1992, Gynecologic oncology.

[17]  R. Knapp,et al.  Unifocal origin of advanced human epithelial ovarian cancers. , 1992, Cancer research.

[18]  P. Humphrey,et al.  Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation. , 1992, Journal of the National Cancer Institute.

[19]  R. Berkowitz,et al.  Molecular genetic evidence of a unifocal origin for human serous ovarian carcinomas. , 1993, Gynecologic oncology.

[20]  R. Kurman,et al.  The behavior of serous tumors of low malignant potential: are they ever malignant? , 1993, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[21]  R. Berkowitz,et al.  Mutation of K-ras protooncogene in human ovarian epithelial tumors of borderline malignancy. , 1993, Cancer research.

[22]  M. Birrer,et al.  p53 and Ki-ras gene mutations in epithelial ovarian neoplasms. , 1993, Cancer research.

[23]  L. Liotta,et al.  Identical allelic loss on chromosome 11q13 in microdissected in situ and invasive human breast cancer. , 1995, Cancer research.

[24]  R. Berkowitz,et al.  Evidence for a multifocal origin of papillary serous carcinoma of the peritoneum. , 1995, Cancer research.

[25]  L. Liotta,et al.  A microdissection technique for archival DNA analysis of specific cell populations in lesions < 1 mm in size. , 1995, The American journal of pathology.

[26]  R. Scully,et al.  Ovarian, peritoneal, and endometrial serous carcinoma: clonal origin of multifocal disease. , 1996, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[27]  M. Sherman,et al.  Micropapillary serous carcinoma of the ovary. A distinctive low-grade carcinoma related to serous borderline tumors. , 1996, The American journal of surgical pathology.

[28]  W. R. Hart,et al.  Ovarian papillary serous tumors of low malignant potential (Serous borderline tumors): A long term follow‐up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma , 1996, Cancer.

[29]  J. Felix,et al.  Potential role of the inactivated X chromosome in ovarian epithelial tumor development. , 1996, Journal of the National Cancer Institute.

[30]  E. Kohn,et al.  Borderline ovarian tumors. , 1996, The American journal of medicine.

[31]  R. Kurman,et al.  Micropapillary Serous Carcinoma of the Ovary , 1997 .

[32]  A. Sood,et al.  Field cancerization: why late "recurrent" ovarian cancer is not recurrent. , 1998, American journal of obstetrics and gynecology.

[33]  G. Chenevix-Trench,et al.  No evidence for microsatellite instability from allelotype analysis of benign and low malignant potential ovarian neoplasms. , 1998, Gynecologic oncology.

[34]  J. Cheville,et al.  Atypical adenomatous hyperplasia of the prostate: a premalignant lesion? , 1998, Cancer research.

[35]  L. Liotta,et al.  Evidence of Independent Origin of Multiple Tumors From Patients With Prostate Cancer , 1998 .

[36]  R. Berkowitz,et al.  Evidence for the multifocal origin of bilateral and advanced human serous borderline ovarian tumors. , 1998, Cancer research.

[37]  R. Scully,et al.  Ovarian serous borderline tumors with micropapillary and cribriform patterns: a study of 40 cases and comparison with 44 cases without these patterns. , 1999, The American journal of surgical pathology.

[38]  A. Sood,et al.  Association between nonrandom X-chromosome inactivation and BRCA1 mutation in germline DNA of patients with ovarian cancer. , 1999, Journal of the National Cancer Institute.