title: Genetic alterations in the peritumoral stromal cells of malignant and borderline epithelial ovarian tumors as indicated by allelic imbalance on chromosome 3p.
abstract: Stromal accumulation of hyaluronan in epithelial ovarian cancers is an independent predictor of tumor spreading and unfavorable outcome of the disease. We started to screen for chromosomal causes of this accumulation by studying deletions in 3p21.3, a region harboring 3 hyaluronidase genes (HYAL1-3) among other potentially important tumor suppressors. Using 6 microsatellite markers from this region, allelic imbalance was found in 60-87% of the informative tumor cells microdissected from histologic sections of 58 patients with epithelial ovarian cancer. However, adjacent stromal cells originally intended as controls showed allelic imbalance at a frequency almost as high as the tumor cells (52-80%). A further laser capture microdissection on 10 borderline tumors also showed a high rate of allelic imbalance, both in the epithelial and stromal cells, but with a pattern slightly different from cancers. Allelic imbalance in the tumor epithelium or stroma was not correlated with the accumulation of hyaluronan or clinicopathologic parameters, including tumor stage and grade. The results suggest that factors other than inactivation of the HYAL1-3 genes are responsible for hyaluronan accumulation in epithelial ovarian tumors. Moreover, the results indicate that the stromal cells of the epithelial ovarian cancers not only respond to the signals from malignant epithelium but also have themselves undergone genetic alterations in markers partly identical to those in the cancer epithelial cells and may actively contribute to the development of the tumor from its early stages to the late determinants of patient mortality.
authors.affiliation: Department of Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Tuhkanen
authors.forename: Maarit
authors.initials: M
authors.lastname: Anttila
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
authors.forename: Arja
authors.initials: A
authors.lastname: Kuronen
authors.forename: Matti
authors.initials: M
authors.lastname: Juhola
authors.forename: Raija
authors.initials: R
authors.lastname: Tammi
authors.forename: Markku
authors.initials: M
authors.lastname: Tammi
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
mesh_terms: D022981:Allelic Imbalance; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics*; D007834:Lasers; D018895:Microsatellite Repeats; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies; D012189:Retrospective Studies; D017154:Stromal Cells / Q000473:pathology
chemical_list: D006821:Hyaluronoglucosaminidase