Combinations of Multiple Serum Markers Are Superior to Individual Assays for Discriminating Malignant from Benign Pelvic Masses

Woolas, Robert; Conaway, Mark R.; Xu, Fengji; Jacobs, Ian; Yang, Yu Shih; Daly, L.; Davies, Anthony; O'Briant, Kathy; Berchuck, Andrew; Soper, John T.; Clarke‐Pearson, Daniel L.; Rodríguez, Gustavo J.; Oram, David; Bast, Robert C.

doi:10.1006/gyno.1995.1276

Cited by 94 publications

(61 citation statements)

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“…Even though KLK6 may not be a strong independent prognostic indicator for ovarian cancer, it appears to be a surrogate marker for other clinicopathological variables such as tumour stage, grade, histotype and debulking success. Recent evidence indicates that multiparametric strategies that merge diagnostic and prognostic information provided by several individual biomarkers yield more informative and accurate medical predictions (Woolas et al, 1993(Woolas et al, , 1995Zhang et al, 1999;Mor et al, 2005). Therefore, KLK6 could be used in conjunction with other kallikreins, as well as non-kallikrein biomarkers in future multiparametric prognostic tests for ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

et al. 2007

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The human tissue kallikrein family (KLK for protein; KLK for gene) includes 15 members. Twelve kallikreins, including KLK6, are concurrently upregulated in ovarian cancer. However, the mechanism of this phenomenon remains unclear. In this study, we measured KLK6 expression in a large series of ovarian tissue cytosols and examined possible mechanisms of KLK6 up-regulation in ovarian cancer. Using a newly developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies, we quantified KLK6 expression in ovarian tissue cytosols, and confirmed the upregulation of KLK6 in ovarian cancer and its unfavourable prognostic value. We then examined KLK6 mRNA expression using reverse transcription -polymerase chain reaction and established its good concordance with KLK6 protein expression. This finding suggested that the KLK6 gene is under transcriptional regulation. We then scrutinised a few mechanisms that could explain KLK6 upregulation. The relative abundance of two KLK6 mRNA transcripts was studied; we found the same differential expression pattern in all samples, regardless of KLK6 levels. Genomic mutation screening of all exons and the 5 0 -flanking region of the KLK6 gene identified two linked single-nucleotide polymorphisms in the 5 0 -untranslated region, but neither correlated with KLK6 expression. Ovarian cell lines were separately treated with five steroid hormones. None of the treatments produced significant effects on KLK6 expression. We conclude that KLK6 is transcriptionally upregulated in ovarian cancer, but probably not through alternative mRNA transcript expression, genomic mutation, or steroid hormone induction.

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Section: Discussionmentioning

confidence: 99%

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

et al. 2007

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“…Combination of marker with CA125 has been reported earlier. In one of the earliest reports, 14 four different markers (CA 15-3, CA72-4, OVX1, LASA) were combined with CA125 and showed a modest increased sensitivity and specificity of 10%. However, the use of 5 different markers is both expensive and laborious.…”

Section: Discussionmentioning

confidence: 99%

“…Various combinations of different tumor markers have shown a higher specificity in differentiating benign from malignant disease. 13,14 However, the efficacy and/or sensitivity of these markers were limited to advanced-stage serous subtype tumors. Therefore, there is a clear need for the identification of additional biomarkers for ovarian cancer.…”

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confidence: 99%

From gene profiling to diagnostic markers: IL‐18 and FGF‐2 complement CA125 as serum‐based markers in epithelial ovarian cancer

Page

Ouellet

Madore

et al. 2005

Intl Journal of Cancer

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We used an oligonucleotide-based DNA microarray to identify potential markers in 39 primary cultures of ovarian cancer specimens compared with 11 primary cultures of normal ovarian epithelia. Differential gene expression of IL-18 and FGF-2 was validated on a subset of samples by quantitative PCR and by IHC, using an independent tissue array of 90 cores of 20 normal ovarian surface epithelia and 70 EOCs representing different grades and pathologies of ovarian disease. We further compared, by ELISA, these two markers with CA125 in sera from 25 cancer-free and 47 ovarian cancer patients. IL-18 and FGF-2 proteins were significantly elevated in tumor tissues (p<0.04) and sera (p<0.05) from patients with ovarian cancer. In combination, the three markers (IL-18, FGF-2, and CA125) showed similar sensitivity in scoring for ovarian cancer (35/45 patients) compared to that of CA125 alone (37/45) and significantly improved the specificity of detection (20/25 patients) compared to each marker individually (15/25 for CA125; 18/25 FGF-2; 16/25 for IL-18). In conclusion we show that a combination of the three serum markers (IL-18, FGF-2 and CA125) is associated with EOC, with higher specificity than CA125 alone. Prospective studies with a large cohort of susceptible ovarian cancer patients will be required to expand these findings. ' 2005 Wiley-Liss, Inc.

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“…However, increased sensitivity is usually associated with decreased specificity. A panel of eight different markers (CA125, M-CSF, OVX1, LASA, CA15-3, CA72-4, CA19-9, CA54/61) improved the sensitivity for discriminating malignant from benign pelvic masses (60). Using the same dataset, a subset of four markers analyzed using an artificial neural network demonstrated improved sensitivity over CA125 alone (87.5% versus 68.4%) while maintaining comparable specificity (61).…”

Section: Ovx1mentioning

confidence: 93%

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Jacobs

Menon

2004

Molecular & Cellular Proteomics

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Ovarian cancer is characterize by few early symptoms, presentation at an advanced stage, and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. During the last decade, a research effort has been directed toward improving outcomes for ovarian cancer by screening for preclinical, early stage disease using both imaging techniques and serum markers. Numerous biomarkers have shown potential in samples from clinically diagnosed ovarian cancer patients, but few have been thoroughly assessed in preclinical disease and screening. The most thoroughly investigated biomarker in ovarian cancer screening is CA125. Prospective studies have demonstrated that both CA125 and transvaginal ultrasound can detect a significant proportion of preclinical ovarian cancers, and refinements in interpretation of results have improved sensitivity and reduced the false-positive rate of screening. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from ovarian cancer is still unclear. Prospective studies of screening are in progress in both the general population and high-risk population, including the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKC-TOCS), a randomized trial involving 200,000 postmenopausal women designed to document the impact of screening on mortality. Recent advances in technology for the study of the serum proteome offer exciting opportunities for the identification of novel biomarkers or patterns of markers that will have greater sensitivity and lead time for preclinical disease than CA125. Considerable interest and controversy has been generated by initial results utilizing surface-enhanced laser desorption/ionization (SELDI) in ovarian cancer. There are challenging issues related to the design of studies to evaluate SELDI and other proteomic technology, as well as the reproducibility, sensitivity, and specificity of this new technology. Large serum banks such as that assembled in UKCTOCS, which contain preclinical samples from patients who later developed ovarian cancer and other disorders, provide a unique resource for carefully designed studies of proteomic technology. There is a sound basis for optimism that further developments in serum proteomic analysis will provide powerful methods for screening in ovarian cancer and many other diseases.

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Combinations of Multiple Serum Markers Are Superior to Individual Assays for Discriminating Malignant from Benign Pelvic Masses

Cited by 94 publications

References 0 publications

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

From gene profiling to diagnostic markers: IL‐18 and FGF‐2 complement CA125 as serum‐based markers in epithelial ovarian cancer

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

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