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Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma.

Prentice LM, Klausen C, Kalloger S, Köbel M, McKinney S, Santos JL, Kenney C, Mehl E, Gilks CB, Leung P, Swenerton K, Huntsman DG, Aparicio SA - BMC Med (2007)

Bottom Line: The latter might suggest that their overexpression would be associated with a better prognosis in cancer.Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p < 0.0001, p < 0.0001), and GPR54 is significantly associated with favourable prognosis in overall survival within the clear cell subtype (p = 0.0102).Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear cell ovarian carcinoma subtype, thereby creating the first independent prognostic biomarkers specific for ovarian clear cell carcinomas.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Oncology and Breast Cancer Program, British Columbia Cancer Research Centre and Department of Pathology, University ofBritish Columbia, Vancouver, British Columbia, Canada. Leah.Prentice@vch.ca

ABSTRACT

Background: Kisspeptins and their G-protein coupled receptor, GPR54 are required for GnRH release and have been associated with anti-metastatic tumour cell behaviour in model systems. The latter might suggest that their overexpression would be associated with a better prognosis in cancer. However, kisspeptin/GPR54 interactions (autocrine, paracrine, and/or endocrine) could also impact tumour behaviour in a negative manner. Here, for the first time, we associate the immunoreactivity of the kisspeptin/GPR54 ligand-receptor pair with favourable prognosis in a large cohort of ovarian carcinomas.

Methods: Immunohistochemical analysis for kisspeptin and GPR54 was performed on a tissue microarray (TMA) consisting of 518 early stage ovarian carcinomas, all with linked clinical outcome data. The TMA was scored using a staining intensity scale of 0 (negative), +1 (mild-moderate), and +2 (strong). Strong staining cases were considered either kisspeptin or GPR54 positive and designated as 1, while all other cases were considered negative and designated 0. All statistical analysis was conducted using two-sided tests and a p value equal to or less than 0.05 was considered significant.

Results: Kisspeptin and GPR54 immunoreactive cases show a favourable prognosis in univariable disease specific survival (p = 0.0023, p = 0.0092), as well as in overall survival (p = 0.0006, p = 0.0002). Furthermore, kisspeptin is an independent marker for favourable prognosis as determined by multivariable disease specific (p = 0.0046) and overall survival analysis (p = 0.0170), while GPR54 is an independent marker for overall survival only (p = 0.0303). Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p < 0.0001, p < 0.0001), and GPR54 is significantly associated with favourable prognosis in overall survival within the clear cell subtype (p = 0.0102).

Conclusion: Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear cell ovarian carcinoma subtype, thereby creating the first independent prognostic biomarkers specific for ovarian clear cell carcinomas.

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Disease specific (left) and overall (right) survival curves for kisspeptin and GPR54. The top two graphs demonstrate the significant survival curves for GPR54, while the middle two graphs demonstrate kisspeptin related survival. For the bottom two graphs, the p value refers to the distance between the GPR54 positive/kisspeptin positive cases (G+ K+, solid light grey) and the GPR54 negative/kisspeptin negative cases (G- K-, solid dark grey).
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Figure 3: Disease specific (left) and overall (right) survival curves for kisspeptin and GPR54. The top two graphs demonstrate the significant survival curves for GPR54, while the middle two graphs demonstrate kisspeptin related survival. For the bottom two graphs, the p value refers to the distance between the GPR54 positive/kisspeptin positive cases (G+ K+, solid light grey) and the GPR54 negative/kisspeptin negative cases (G- K-, solid dark grey).

Mentions: For the 518 case ovarian tissue microarray, kisspeptin-IR was scored as 0 for negative cases, +1 for mild staining, and +2 for intense staining (Figure 2). Of the 518 cases, 44 stained at +2, 98 had +1 staining intensity, 354 cases were negative for kisspeptin-IR, and 22 cases were uninterpretable. The negative (0) and mildly reactive (+1) cases were grouped for statistical analysis and assigned the designation 0 and considered kisspeptin negative, while the +2 cases were considered kisspeptin positive and designated as 1. Univariable disease specific survival analysis showed that kisspeptin-IR significantly associated with favourable prognosis (p = 0.0023), as did overall survival (p = 0.0006, Figure 3). Further, multivariable survival analysis including; stage, grade, histological subtype, age and GPR54-IR, indicated kisspeptin-IR as an independent marker for favourable prognosis in disease specific (p = 0.0046, Table 2) and overall survival (p = 0.0170, Table 3).


Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma.

Prentice LM, Klausen C, Kalloger S, Köbel M, McKinney S, Santos JL, Kenney C, Mehl E, Gilks CB, Leung P, Swenerton K, Huntsman DG, Aparicio SA - BMC Med (2007)

Disease specific (left) and overall (right) survival curves for kisspeptin and GPR54. The top two graphs demonstrate the significant survival curves for GPR54, while the middle two graphs demonstrate kisspeptin related survival. For the bottom two graphs, the p value refers to the distance between the GPR54 positive/kisspeptin positive cases (G+ K+, solid light grey) and the GPR54 negative/kisspeptin negative cases (G- K-, solid dark grey).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2200658&req=5

Figure 3: Disease specific (left) and overall (right) survival curves for kisspeptin and GPR54. The top two graphs demonstrate the significant survival curves for GPR54, while the middle two graphs demonstrate kisspeptin related survival. For the bottom two graphs, the p value refers to the distance between the GPR54 positive/kisspeptin positive cases (G+ K+, solid light grey) and the GPR54 negative/kisspeptin negative cases (G- K-, solid dark grey).
Mentions: For the 518 case ovarian tissue microarray, kisspeptin-IR was scored as 0 for negative cases, +1 for mild staining, and +2 for intense staining (Figure 2). Of the 518 cases, 44 stained at +2, 98 had +1 staining intensity, 354 cases were negative for kisspeptin-IR, and 22 cases were uninterpretable. The negative (0) and mildly reactive (+1) cases were grouped for statistical analysis and assigned the designation 0 and considered kisspeptin negative, while the +2 cases were considered kisspeptin positive and designated as 1. Univariable disease specific survival analysis showed that kisspeptin-IR significantly associated with favourable prognosis (p = 0.0023), as did overall survival (p = 0.0006, Figure 3). Further, multivariable survival analysis including; stage, grade, histological subtype, age and GPR54-IR, indicated kisspeptin-IR as an independent marker for favourable prognosis in disease specific (p = 0.0046, Table 2) and overall survival (p = 0.0170, Table 3).

Bottom Line: The latter might suggest that their overexpression would be associated with a better prognosis in cancer.Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p < 0.0001, p < 0.0001), and GPR54 is significantly associated with favourable prognosis in overall survival within the clear cell subtype (p = 0.0102).Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear cell ovarian carcinoma subtype, thereby creating the first independent prognostic biomarkers specific for ovarian clear cell carcinomas.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Oncology and Breast Cancer Program, British Columbia Cancer Research Centre and Department of Pathology, University ofBritish Columbia, Vancouver, British Columbia, Canada. Leah.Prentice@vch.ca

ABSTRACT

Background: Kisspeptins and their G-protein coupled receptor, GPR54 are required for GnRH release and have been associated with anti-metastatic tumour cell behaviour in model systems. The latter might suggest that their overexpression would be associated with a better prognosis in cancer. However, kisspeptin/GPR54 interactions (autocrine, paracrine, and/or endocrine) could also impact tumour behaviour in a negative manner. Here, for the first time, we associate the immunoreactivity of the kisspeptin/GPR54 ligand-receptor pair with favourable prognosis in a large cohort of ovarian carcinomas.

Methods: Immunohistochemical analysis for kisspeptin and GPR54 was performed on a tissue microarray (TMA) consisting of 518 early stage ovarian carcinomas, all with linked clinical outcome data. The TMA was scored using a staining intensity scale of 0 (negative), +1 (mild-moderate), and +2 (strong). Strong staining cases were considered either kisspeptin or GPR54 positive and designated as 1, while all other cases were considered negative and designated 0. All statistical analysis was conducted using two-sided tests and a p value equal to or less than 0.05 was considered significant.

Results: Kisspeptin and GPR54 immunoreactive cases show a favourable prognosis in univariable disease specific survival (p = 0.0023, p = 0.0092), as well as in overall survival (p = 0.0006, p = 0.0002). Furthermore, kisspeptin is an independent marker for favourable prognosis as determined by multivariable disease specific (p = 0.0046) and overall survival analysis (p = 0.0170), while GPR54 is an independent marker for overall survival only (p = 0.0303). Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p < 0.0001, p < 0.0001), and GPR54 is significantly associated with favourable prognosis in overall survival within the clear cell subtype (p = 0.0102).

Conclusion: Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear cell ovarian carcinoma subtype, thereby creating the first independent prognostic biomarkers specific for ovarian clear cell carcinomas.

Show MeSH
Related in: MedlinePlus