Tumor Spreading to the Contralateral Ovary in Bilateral Ovarian Carcinoma Is a Late Event in Clonal Evolution

Abstract

Cancer of the ovary is bilateral in 25%. Cytogenetic analysis could determine whether the disease in bilateral cases is metastatic or two separately occurring primary tumors, but karyotypic information comparing the two cancerous ovaries is limited to a single report with 11 informative cases. We present a series of 32 bilateral ovarian carcinoma cases, analyzed by karyotyping and high-resolution CGH. Our karyotypic findings showed that spreading to the contralateral ovary had occurred in bilateral ovarian cancer cases and that it was a late event in the clonal evolution of the tumors. This was confirmed by the large number of similar changes detected by HR-CGH in the different lesions from the same patient. The chromosomal bands most frequently involved in structural rearrangements were 19p13 (n = 12) and 19q13 (n = 11). The chromosomal bands most frequently gained by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12 (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%). This is the first time that 5p14 is seen gained at such a high frequency in cancer of the ovary; possibly oncogene(s) involved in bilateral ovarian carcinogenesis or tumor progression may reside in this band.

New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination

“…Consistent with a role of the ovary in metastatic disease in human disease, early bilateral intra-ovarian tumors (not merely on the surface of the ovary) are commonly seen (35) and in fact constitute their own stage of disease (stage 1b). These tumors appear clonally related therefore are not likely separate primaries (36, 37). …”

Bilateral ovarian carcinomas differ in the expression of metastasis-related genes

“…The present gene expression results were compared with previously reported genomic analyses of the same material (7). CGH analysis provided copy number information at a resolution level of ~300 cytobands.…”

“…Tumor grade and histology were revised by a gynecological pathologist (Table I). The same material had previously been examined by karyotyping and comparative genomic hybridization (CGH) (7). The tumors were surgically removed at The Norwegian Radium Hospital (Oslo, Norway) between January 2001 and December 2004.…”

“…The results were compared with previous genomic data on the same tumors (7) with the aim of identifying possible mechanisms behind the RNA level differences.…”

Xenotransplantation of cryopreserved ovarian tissue from patients with ovarian tumors into SCID mice—no evidence of malignant cell contamination

“…In patients with ovarian tumors, the risk of reintroducing malignant disease via the transplanted tissue appears to be high, in view of the fact that bilateral carcinomas of the ovary can be found in roughly 25% of all cases of ovarian cancer (27). Collecting immature oocytes from the cryopreserved tissue might in theory be an alternative for these patients.…”