Allelic loss at 19q12 and Xq11-12 predict an adverse clinical outcome in patients with mucinous ovarian tumours of low malignant potential.
Ovarian tumours of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas. These tumours are often associated with a significantly better prognosis than ovarian carcinomas. However, a subset of these tumours can progress and become lethal. In order to seek sensitive diagnostic tools for monitoring patients after surgical operation, we performed a genome-wide scan for loss of heterozygosity (LOH) in 41 mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reportedly associated with ovarian carcinoma. In addition, we assessed whether clinicopathological parameters, microvessel density, Ki-67 labeling index, apoptotic index or p53 overexpression would be useful for predicting the postoperative outcome of LMP patients. Of the 116 markers examined, 19q12 and Xq11-12 showed significant correlation between postoperative progression-free survival time and LOH status (P<0.05). Patients with a high Ki-67 labeling index had a significantly poorer progression-free survival time than those with lower levels (P=0.042). Other clinicopathological factors and immunohistochemical analysis had no correlation with progression-free survival time in this series of patients. When the combination of LOH at 19q12 and/or Xq11-12 was assessed using Cox's regression analysis, patients with tumours that showed LOH at these positions were at greatest risk of progression (P=0.0073). These findings suggest that the identification of LOH at 19q12 and/or Xq11-12 in former mucinous LMP sites should alert the clinician to the presence of a potentially aggressive lesion in the coelomic epithelium, even if a distinction between second primary tumours or recurrence could not be determined.
Nakayama
K
K
Department of Obstetrics and Gynecology, Shimane Medical University, Enyacho 89-1, Izumo 693-8501, Japan. kn88@shimane-med.ac.jp
Takebayashi
Y
Y
Hata
K
K
Fujiwaki
R
R
Iida
K
K
Fukumoto
M
M
Miyazaki
K
K
D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D002888:Chromosomes, Human, Pair 19; D041321:Chromosomes, Human, X; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors
D005819:Genetic Markers