Comparing the genetic changes detected in the primary and secondary tumor sites of ovarian cancer using comparative genomic hybridization

Purpose: Seventy percent of all ovarian cancer (OvCa) diseases are diagnosed at an advanced stage due to poor screening methods. In general, the therapy consists of cyto-reductive surgery followed by first line platinum based chemo therapy, which frequently leads to a long-term response. A resistance against platinum therapy was detected in some cases by refractory recurrence within six months after the last donation. Identifying a marker predicting platinum effectiveness could be of great benefit for affected patients.Patients and methods: In this study we propose cyto-genetic procedures identifying markers of platinum resistance. Fresh tumor material was obtained from nine OvCa patients. After the last platinum-based chemotherapy, five patients had refractory recurrence within six month. DNA was isolated from tumor tissues for array-based comparative genomic hybridization (aCGH) analysis. Ten cultured metaphases per case were analyzed by spectral karyotyping (SKY) to detect repeated chromosome rearrangements. The obtained genomic data were correlated to the patients’ clinical follow-up data.Results: Eight chromosome aberrations correlated with recurrence later than six months were detected in tumors by SKY. Further seven chromosome aberrations correlated with a refractory recurrence. Non refractory tumors more frequently showed losses in 19q13.31-q13.42 by aCGH. Tumors with refractory recurrence more frequently showed gains in 17q21.32-17q24.3 and losses in 14q11.2, 9p22-p21.1, and 1p22.3-p22.1. OvCa showed separating cyto-genetic changes differentiated in platinum-refractory and non-refractory cases.Conclusion: Our results suggest that aCGH is the most suitable strategy for this, due to a significantly higher resolution. The loss in 19q13 correlated with better prognosis in OvCa

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Pituicytoma: Characterization of a Unique Neoplasm by Histology, Immunohistochemistry, Ultrastructure, and Array-Based Comparative Genomic Hybridization

Archives of Pathology & Laboratory Medicine ◽

10.5858/2009-0167-cr.1 ◽

2010 ◽

Vol 134 (7) ◽

pp. 1063-1069 ◽

Cited By ~ 1

Author(s):

Joanna J. Phillips ◽

Anjan Misra ◽

Burt G. Feuerstein ◽

Sandeep Kunwar ◽

Tarik Tihan

Keyword(s):

Comparative Genomic Hybridization ◽

Copy Number ◽

Secretory Granules ◽

Comparative Genomic ◽

Sellar Region ◽

Genomic Hybridization ◽

Genetic Changes ◽

Genomic Copy Number ◽

Genomic Copy

Abstract The pituicytoma is a rare neoplasm whose histogenesis is debated partly because of the diversity of tissue types present in the sellar region. In this article we illustrate the characteristic histologic, immunohistologic, and ultrastructural features of this unique neoplasm. Furthermore, we use array-based comparative genomic hybridization to demonstrate a unique pattern of genomic copy number aberrations in pituicytomas. Tumors were composed of bipolar, spindle cells that were immunopositive for S100, vimentin, and Bcl-2 and immunonegative for synaptophysin, chromogranin, and glial fibrillary acidic protein. Ultrastructural analysis was remarkable for absence of secretory granules. Array comparative genomic hybridization demonstrated genomic copy number imbalances, including losses on chromosome arms 1p, 14q, and 22q and gains on 5p. This pattern of genetic changes only partially overlaps with the genomic alterations reported in pituitary adenomas. In summary, our data suggest that pituicytomas are a unique subset of tumors of the sellar region.

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