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To determine the CA125 tissue expression levels in borderline and invasive epithelial ovarian tumor tissues. Secondly, to evaluate whether CA125 tissue expression levels correlate with clinico-pathological parameters and serum CA125 levels and finally to investigate the prognostic value of tissue CA125 expression levels in ovarian cancer (OC) patients.We designed tissue arrays (TA) and analyzed the CA125 expression in tissues from 778 Danish women with an ovarian tumor. Furthermore, corresponding preoperative blood samples obtained before surgery were collected from 382 women with OC.Significantly more CA125 expression positive tumors (no expression vs. expression) were found in the serous subtype compared to the percentage of positive tumors in mucinous, endometroid and other subtypes for patients both with borderline ovarian tumors and with OC (p0.00001, p0.00001). Similarly, a positive significant correlation was found between elevated serum CA125 levels and elevated levels of CA125 tissue expression (N=382 stage I-IV OC, Spearman rho=0.31, p0.0001) (N=206 stage III OC, Spearman rho=0.30, p0.0001). We found a significantly shorter survival for stage III/IV OC patients with no CA125 tissue expression compared to stage III/IV OC patients with positive CA125 tissue expression (p=0.0003).Our finding that tissue CA125 expression was lacking in late stage primary OC tumor of Danish women with poor survival may be of value in selecting patients as eligible candidates for individually based treatments.

The p53 gene, a tumor suppressor gene located on the short arm of chromosome 17 (17p13), has been found mutated in 30-80% of epithelial ovarian cancers (OC), with the most frequently detected mutations in the conserved regions of the gene. A small number of studies investigated the survival of patients with p53 mutations in OC, but their conclusions are not in agreement.We analyzed the frequency of p53 mutations in 124 Danish women with OC, using Single-Stranded Conformation Polymorphism analysis in addition with DNA sequencing and evaluated if mutations correlated with clinicopathological parameters and with patient survival.Thirty-five (28%) ovarian tumors were found to contain one or more p53 variations, two of which were considered polymorphisms. Twenty-seven (82%) mutations were single nucleotide substitutions of which 23 (85%) were missense mutations and therefore led to amino acid substitutions. Significantly shorter survival was found for stage III/IV patients with a p53 missense mutation compared to stage III/IV OC patients with wild type p53 (P = 0.0018). Multivariate Cox regression analysis restricted to 107 OC patients with a p53 missense mutation or p53 wild type in the tumor tissue and with information on radicality of primary surgery showed that missense p53 mutation (HR = 2.5, 95% CI: 1.21-4.98), radicality after primary surgery (HR = 1.7, 95% CI: 1.04-2.88), tetranectin (mg/l: HR = 0.78, 95% CI: 0.67-0.91) and stage (I vs. III: HR = 0.30, 95% CI: 0.10-0.92, II vs. III: HR = 0.24, 95% CI: 0.05-1.05, IV vs. III: HR = 2.70, 95% CI: 1.22-5.98) were independent prognostic factors.Missense mutations in the conserved regions of p53 may be of prognostic value in Danish OC patients.

YKL-40, a member of family 18 glycosyl hydrolases, is secreted by cancer cells. The function of YKL-40 in cancer diseases is unknown, but it is a growth factor of connective tissue cells and probably has a role in inflammation and remodeling of the extracellular matrix, a process also involved in metastatic malignant diseases. High serum YKL-40 has been associated with poor prognosis for patients with colorectal and recurrent breast cancer.The purpose of the present study was to examine the prognostic value of plasma YKL-40 in patients presenting with recurring ovarian cancer.YKL-40 was determined by ELISA in plasma samples from 73 patients with relapse of ovarian cancer shortly before start of second-line chemotherapy. The endpoint used was death because of ovarian cancer.Plasma YKL-40 was increased in ovarian cancer patients (median 94 micro g/L, range 20-1970 micro g/L) compared with age-matched controls (33 micro g/L, range 20-130 micro g/L) (p0.001). Fifty-five per cent of the patients had a plasma YKL-40 level above the upper normal 95th percentile of controls. Patients with high plasma YKL-40 (i.e.130 micro g/L or160 micro g/L) at the time of relapse had significantly shorter survival than patients with normal levels (respectively p = 0.007 and p = 0.004). Plasma YKL-40 proved to be an independent prognostic factor in a multivariate Cox analysis (YKL-40160 micro g/L; HR = 2.27) (p = 0.006), including serum CA-125 and clinical/histological parameters.High plasma YKL-40 is related to short survival in patients with recurrent ovarian cancer.

The p53 gene is frequently mutated in various human tumours. In addition, single nucleotide polymorphisms are often observed in exons and introns of the p53 gene in normal tissues and tumours.The prevalence of a polymorphism involving codon 72 of exon 4 in the p53 gene was studied in peripheral white blood cells and tumour tissues from Danish ovarian tumour patients and in peripheral white blood cells from controls. The analyses were performed by Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) and DNA sequencing. The amino acid residue at this position is either arginine (p53-Arg) or proline (p53-Pro).There was no correlation between the frequency of the three genotypes (Pro/Pro, Arg/Arg and Arg/Pro) and age, stage or histological type of the tumour. A significant difference in survival was observed between ovarian cancer stage III patients with a shift from one genotype in the blood to another genotype in the tissue and patients with no shift (p=0.0216).Kaplan-Meier survival analyses and multivariate Cox regression analysis stratified to stage III ovarian cancer patients showed that a shift from one genotype in the blood to another genotype in the tissue is a prognostic factor in Danish ovarian cancer patients.