Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas

Schummer, Michèl; Ng, Wai Lap; Bumgarner, Roger E.; Nelson, Peter S.; Schummer, Bernhard; Bednarski, David W.; Hassell, Laurie; Baldwin, Roger A.; Karlan, Beth Y.; Hood, Leroy

doi:10.1016/s0378-1119(99)00342-x

Cited by 351 publications

(224 citation statements)

References 24 publications

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“…Wang et al (1999) and also used cDNA microarrays to monitor gene expression changes in ovarian tumours compared to normal ovaries. There were no common genes between those identified in our study and those in the top 15 overexpressed or under-expressed known genes reported by Wang et al (1999) or the 43 known genes found to be over-expressed by Schummer et al (1999). This may be a reflection of the different cDNAs included in the respective arrays.…”

Section: Discussionmentioning

confidence: 54%

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

et al. 2001

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SummaryThe molecular events that drive the initiation and progression of ovarian adenocarcinoma are not well defined. We have investigated changes in gene expression in ovarian cancer cell lines compared to an immortalized human ovarian surface epithelial cell line (HOSE) using a cDNA array. We identified 17 genes that were under-expressed and 10 genes that were over-expressed in the cell lines compared to the HOSE cells. One of the genes under-expressed in the ovarian cancer cell lines, Id3, a transcriptional inactivator, was selected for further investigation. Id3 mRNA was expressed at reduced levels in 6 out of 9 ovarian cancer cell lines compared to the HOSE cells while at the protein level, all 7 ovarian cancer cell lines examined expressed the Id3 protein at greatly reduced levels. Expression of Id3 mRNA was also examined in primary ovarian tumours and was found in only 12/38 (32%) cases. A search was conducted for mutations of Id3 in primary ovarian cancers using single stranded conformation polymorphism (SSCP) analysis. Only one nucleotide substitution, present also in the corresponding constitutional DNA, was found in 94 ovarian tumours. Furthermore no association was found between LOH at 1p36 and lack of expression of Id3. These data suggest that Id3 is not the target of LOH at 1p36.

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Section: Discussionmentioning

confidence: 54%

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

et al. 2001

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“…Recently, microarray based approaches have been used to assemble multigene expression profiles of neoplastic ovarian tissue. Such studies have identified the gene coding for HE4, a secreted extracellular protease inhibitor, as a promising diagnostic marker (Ono et al, 2000) and pinpointed other genes that correlate with serous and mucinous histology (Schummer et al, 1999). A recent report (Welsh et al, 2001) analysed the expression levels of more than 6000 human genes in 27 ovarian tumours and four normal ovarian tissue samples using this technique.…”

Section: Discussionmentioning

confidence: 99%

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

et al. 2002

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Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg 71 total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (435 ng hK6 mg 71 total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg 71 total protein) was higher in late stage disease, serous histotype, residual tumour 41 cm and suboptimal debulking (41 cm) (P50.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis.

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“…Human epidydimis secretory protein 4 is an 11-kDa protein, which is localized on chromosome 20q12 (Schummer et al, 1999). For the first it was identified in epidydimis epithelium and its function was initially associated with the maturation of sperm involved in protease inhibition (Kirchhoff et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…There are several explanations why human epidydimis secretory protein 4 is more sensitive in comparison to CA125. HE4 is a high molecular weight glycoprotein with an approximate molecular mass 80 kDa, but its secreted form is a 11 kDa protein, that explains an earlier release of biomarker in the blood stream (Schummer et al, 1999). Earlier appearance of human epidydimis secretory protein 4 in the serum in case of early stage ovarian cancer is likely to be associated with a simpler mechanism for its release (Boshell et al, 1992;Ligtenberg et al, 1992;Yin et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Urinary Concentrations of Human Epidydimis Secretory Protein 4 (He4) in The Diagnosis of Ovarian Cancer: A Case-Control Study

Macuks

Baidekalna²,

Doniņa³

2012

Asian Pacific Journal of Cancer Prevention

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Objective: To analyze differential diagnostic accuracy of urinary human epidydimis secretory protein 4 (HE4) in patients with ovarian tumors. Materials and methods: In the case-control study 23 patients with ovarian cancer, 37 patients with benign ovarian tumors and 18 women in the control group were included. Serum CA125 values and urinary concentrations of HE4were assessed quantitatively. Urinary creatinine concentrations and glomerular filtration rate were also determined and used to calculate ratios to HE4. Results: Higher urinary HE4 concentrations were observed in patients with late stage ovarian cancer (p=0.001) and also in patients with early stage ovarian cancer when compared to patients with benign ovarian tumors (p=0.044). On analysis where all ovarian cancer patients were included, higher diagnostic accuracy was observed with calculated ratio of HE4 to glomerular filtration rate (GFR) to unchanged urinary HE4 concentrations -AUC 0.861 vs. 0.858. When discriminatory accuracy was calculated for urinary HE4/GFR ratio and unchanged urinary HE4 concentrations, the last demonstrated a higher area under the curve -0.701 vs. 0.602. The urinary HE4/creatinine ratio had lower discriminatory characteristics than unchanged concentrations of urinary HE4. However, HE4 serum concentration was more accurate for discrimination of patients with benign and malignant ovarian tumors when compared to urinary HE4 and CA125 in sera (AUCs were 0.868 for serum HE4 and 0.856 and 0.653 for urinary HE4 and CA125, respectively). Conclusions: Ovarian cancer patients have higher urinary concentrations of human epidydimis secretory protein 4 than patients with benign ovarian tumors. Urinary HE4 has comparable discriminatory accuracy with serum HE4 for benign and malignant ovarian tumors and can be recommended as a non-invasive ovarian cancer risk assessment method.

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Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas

Cited by 351 publications

References 24 publications

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

Urinary Concentrations of Human Epidydimis Secretory Protein 4 (He4) in The Diagnosis of Ovarian Cancer: A Case-Control Study

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