Relative concentrations of hK2/PSA mRNA in benign and malignant prostatic tissue

Lintula, Susanna; Stenman, Jakob; Bjartell, Anders; Nordling, Stig; Stenman, Ulf‐Hǎkan

doi:10.1002/pros.20194

Cited by 45 publications

(25 citation statements)

References 37 publications

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“…They found more intense hK2-specific immunostaining in lymphatic metastases and in high-grade tumors compared with well-differentiated tumors and benign tissue, whereas contrary findings were reported for PSA (8 ). Herrala et al quantified expression by a conceptually different approach; in situ hybridization revealed that hK2 was expressed at higher concentrations in PCa tissue compared with benign prostate tissue (P Ͻ0.0005), (10 ). In their study, the ratio of hK2:PSA mRNA was significantly higher in cancer than in benign tissue (P ϭ 0.03) and higher still in high-grade PCa (P ϭ 0.006) (10 ).…”

Section: Discussionmentioning

confidence: 94%

“…Herrala et al quantified expression by a conceptually different approach; in situ hybridization revealed that hK2 was expressed at higher concentrations in PCa tissue compared with benign prostate tissue (P Ͻ0.0005), (10 ). In their study, the ratio of hK2:PSA mRNA was significantly higher in cancer than in benign tissue (P ϭ 0.03) and higher still in high-grade PCa (P ϭ 0.006) (10 ). This finding suggests that changes in relative expression of hK2 vs PSA may be associated with carcinogenesis and progression, hence providing further evidence that hK2 might be a useful biomarker for PCa and, in particular, advanced disease.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

et al. 2007

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Background:We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis. Methods: We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA <10 g/L, the group most commonly seen in clinical practice in the US, was analyzed. Results: thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA,

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

et al. 2007

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“…With this type of experimental setup the relative amounts of the amplification products remain unchanged throughout amplification and reflect the proportions of mRNA transcripts originally present in the sample. 24,25 Our method is linear from 1 to 10,000 copies of target cDNA, allowing analysis of low-level variation in the expression of the hCG␤ genes.…”

Section: Discussionmentioning

confidence: 99%

Expression Of Human Chorionic Gonadotropin β-Subunit Type I Genes Predicts Adverse Outcome In Renal Cell Carcinoma

Hotakainen

Lintula

Ljungberg

et al. 2006

The Journal of Molecular Diagnostics

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Expression of the free ␤-subunit of human chorionic gonadotropin (hCG␤) in malignant tumors is frequently associated with aggressive disease. The pretreatment serum concentration of hCG␤ is an independent prognostic variable in renal cell carcinoma (RCC). The three so-called type II genes (hCG␤ 3/9, 5, and 8) have been shown to be up-regulated in relation to type I genes (hCG␤ 6/7) in some malignant tumors. We developed a reverse transcription-polymerase chain reaction method for quantification of relative levels of the mRNAs for the two types of hCG␤ genes and studied the association between the expression in RCC tissue (n ‫؍‬ 104) and clinical outcome. hCG␤ mRNA expression was detected in 40% (42 of 104) of the tumors, and in 40 of these (93%), this consisted of hCG␤ type I mRNA only, whereas type II hCG␤ mRNA was detected in two samples. hCG␤ mRNA expression was significantly associated with a shorter diseasespecific (log-rank P ‫؍‬ 0.023; median survival 1.4 versus 7.9 years) and overall survival (log-rank P ‫؍‬ 0.011). In a Cox regression model, stage (P < 0.0001) and hCG␤ mRNA expression (P < 0.0001) were independent prognostic variables. We conclude that expression of type I hCG␤ genes indicates adverse prognosis in

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“…Kallikrein 2 and PSA may be restricted to humans and dogs, which is interesting given the notably-high prevalence of prostate cancer in these two species [63]. Both of these genes are under androgen control and have been implicated as important loci involved in prostate cancer [64,65]. Kallikrein 2 expression is elevated in prostate cancer [64,65], and recent evidence connects polymorphism at this locus to increased risk of prostate cancer [66].…”

Section: Review Of Previous Researchmentioning

confidence: 99%

“…Both of these genes are under androgen control and have been implicated as important loci involved in prostate cancer [64,65]. Kallikrein 2 expression is elevated in prostate cancer [64,65], and recent evidence connects polymorphism at this locus to increased risk of prostate cancer [66]. Prostate specific antigen (in combination with KLK4) may increase tumor cell migration, specifically in association with prostate cancer [67], although it may act as a tumor suppressor in other contexts [68].…”

Section: Review Of Previous Researchmentioning

confidence: 99%

The androgen receptor and prostate cancer: A role for sexual selection and sexual conflict?

Summers

Crespi

2008

Medical Hypotheses

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Summary We propose and evaluate the hypothesis that the CAG repeat region of the androgen receptor represents a locus of antagonistic pleiotropy in the context of sexual selection and sexual conflict. Short repeats are associated with increased transactivation of the androgen receptor at the molecular level, and increased fertility at the phenotypic level. However, short repeats are also associated with increased risk of prostate cancer, and with more aggressive forms of the disease. The somatic evolution of cancer cell lineages also shows a repeated pattern of shortening of the CAG repeat in association with cancer progression, apparently as a result of positive selection among cell lineages. We further postulate that other genes associated with prostate cancer are likely to mediate antagonistic pleiotropy in the context of sexual selection and sexual conflict. A key prediction of this hypothesis is that the genes mediating antagonistic pleiotropy will show historical evidence of positive selection, particularly in the context of sexual conflict. Previous research on the molecular evolution of specific genes associated with prostate cancer supports this prediction, and we suggest further critical tests of the role for genomic conflicts and tradeoffs in the evolution of cancer risk.

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Relative concentrations of hK2/PSA mRNA in benign and malignant prostatic tissue

Abstract: The new quantitative RT-PCR technique facilitates very accurate quantitation of the relative mRNA levels of homologous genes. Using this method we have shown that the ratio of hK2/PSA mRNA is higher in cancerous than in benign prostatic tissue.

Cited by 45 publications

References 37 publications

Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

Expression Of Human Chorionic Gonadotropin β-Subunit Type I Genes Predicts Adverse Outcome In Renal Cell Carcinoma

The androgen receptor and prostate cancer: A role for sexual selection and sexual conflict?

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