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Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma.
Clin Cancer Res. 2001 Aug; 7(8):2372-9.CC

Abstract

PURPOSE

Human kallikrein 10 (hK10; also known as the normal epithelial cell-specific 1 gene and protein) is a secreted serine protease, which belongs to the human kallikrein family. It has been reported that hK10 is down-regulated in breast and prostate cancer cell lines and that it may function as a tumor suppressor. Recently, we developed a highly sensitive and specific immunoassay for hK10 and found that this protein is abundantly expressed in ovarian tissue. In this study, we measured quantitatively hK10 levels in ovarian cancer cytosolic extracts and evaluated the prognostic value of this biomarker in ovarian cancer.

EXPERIMENTAL DESIGN

Specimens from eight normal ovarian tissues, eight ovarian tissues with benign disease, and 182 ovarian tumors were investigated.

RESULTS

hK10 concentration in ovarian tumor cytosols ranged from 0 to 84 ng/mg of total protein, with a median of 2.6. This median was highly elevated in comparison with normal and benign ovarian tissues (P < 0.001). A cutoff of 1.35 ng/mg was selected to categorize tumors as hK10 high and hK10 low. With chi(2) test and Fisher's exact test, high concentration hK10 was found to be associated with advanced disease stage, serous histological type, suboptimal debulking, and large residual tumor (>1 cm; all P < 0.05). hK10 status was additionally correlated with clinical outcome, including progression-free (PFS) and overall survival (OS) using the Cox model. In univariate analysis, we found that patients with hK10 high tumors were more likely to die and relapse, in comparison with patients with hK10 low tumors (hazards ratios for PFS and OS were 1.93 and 2.42, respectively; P < 0.05). Although this correlation disappeared after the entire patient population was subjected to multivariate analysis, it remained significant in the subgroup of patients with stage III/IV ovarian cancer (hazards ratios for PFS and OS were 1.98 and 2.12, respectively; P < 0.05).

CONCLUSIONS

Our results indicate that hK10 is a new, independent, unfavorable prognostic marker, especially for late-stage ovarian cancer.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11489815

Citation

Luo, L Y., et al. "Prognostic Value of Human Kallikrein 10 Expression in Epithelial Ovarian Carcinoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 7, no. 8, 2001, pp. 2372-9.
Luo LY, Katsaros D, Scorilas A, et al. Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma. Clin Cancer Res. 2001;7(8):2372-9.
Luo, L. Y., Katsaros, D., Scorilas, A., Fracchioli, S., Piccinno, R., Rigault de la Longrais, I. A., Howarth, D. J., & Diamandis, E. P. (2001). Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 7(8), 2372-9.
Luo LY, et al. Prognostic Value of Human Kallikrein 10 Expression in Epithelial Ovarian Carcinoma. Clin Cancer Res. 2001;7(8):2372-9. PubMed PMID: 11489815.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma. AU - Luo,L Y, AU - Katsaros,D, AU - Scorilas,A, AU - Fracchioli,S, AU - Piccinno,R, AU - Rigault de la Longrais,I A, AU - Howarth,D J, AU - Diamandis,E P, PY - 2001/8/8/pubmed PY - 2001/10/19/medline PY - 2001/8/8/entrez SP - 2372 EP - 9 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 7 IS - 8 N2 - PURPOSE: Human kallikrein 10 (hK10; also known as the normal epithelial cell-specific 1 gene and protein) is a secreted serine protease, which belongs to the human kallikrein family. It has been reported that hK10 is down-regulated in breast and prostate cancer cell lines and that it may function as a tumor suppressor. Recently, we developed a highly sensitive and specific immunoassay for hK10 and found that this protein is abundantly expressed in ovarian tissue. In this study, we measured quantitatively hK10 levels in ovarian cancer cytosolic extracts and evaluated the prognostic value of this biomarker in ovarian cancer. EXPERIMENTAL DESIGN: Specimens from eight normal ovarian tissues, eight ovarian tissues with benign disease, and 182 ovarian tumors were investigated. RESULTS: hK10 concentration in ovarian tumor cytosols ranged from 0 to 84 ng/mg of total protein, with a median of 2.6. This median was highly elevated in comparison with normal and benign ovarian tissues (P < 0.001). A cutoff of 1.35 ng/mg was selected to categorize tumors as hK10 high and hK10 low. With chi(2) test and Fisher's exact test, high concentration hK10 was found to be associated with advanced disease stage, serous histological type, suboptimal debulking, and large residual tumor (>1 cm; all P < 0.05). hK10 status was additionally correlated with clinical outcome, including progression-free (PFS) and overall survival (OS) using the Cox model. In univariate analysis, we found that patients with hK10 high tumors were more likely to die and relapse, in comparison with patients with hK10 low tumors (hazards ratios for PFS and OS were 1.93 and 2.42, respectively; P < 0.05). Although this correlation disappeared after the entire patient population was subjected to multivariate analysis, it remained significant in the subgroup of patients with stage III/IV ovarian cancer (hazards ratios for PFS and OS were 1.98 and 2.12, respectively; P < 0.05). CONCLUSIONS: Our results indicate that hK10 is a new, independent, unfavorable prognostic marker, especially for late-stage ovarian cancer. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/11489815/Prognostic_value_of_human_kallikrein_10_expression_in_epithelial_ovarian_carcinoma_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=11489815 DB - PRIME DP - Unbound Medicine ER -