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Favorable prognostic value of tissue human kallikrein 11 (hK11) in patients with ovarian carcinoma.
Int J Cancer. 2003 Sep 10; 106(4):605-10.IJ

Abstract

Human kallikrein 11 (hK11/trypsin-like serine protease/TLSP, encoded by the KLK11 gene) is a member of the kallikrein family of secreted serine proteases. Recently, we developed a highly sensitive and specific immunoassay for hK11 and found that this protease is expressed in the prostate, stomach and trachea as well as in amniotic fluid and milk of lactating women. Elevated serum hK11 levels were found in 60% of men with prostate cancer and 70% of women with ovarian cancer. Also, hK11 expression was found to be under the regulation of steroid hormones, particularly estrogens, at the level of KLK11 transcription. We hypothesized that hK11 may be implicated in endocrine-related malignancies and serve as a novel prostate and ovarian cancer serological marker. The aim of our study was to examine if hK11 expression in ovarian tumors bears any prognostic significance. The concentration of hK11 (ng per mg of total protein) in 104 ovarian tumor cytosolic extracts was quantified and correlated with clinicopathologic variables and outcome over a median follow-up period of 67 months. Outcome was defined as progression-free survival (PFS) and overall survival (OS). hK11 concentration in ovarian tumor cytosols ranged from 0-21 ng/mg of total protein, with a median of 0.54 ng/mg. An optimal cutoff value of 0.54 ng/mg was selected to categorize tumors as hK11-positive or -negative. hK11-positive tumors were more frequently associated with early stage (Stage I/II) disease, pre-/peri-menopausal status and patients who exhibited complete or partial response to chemotherapy (p < 0.05). Univariate analysis revealed that patients with hK11-positive tumors had a significantly decreased risk of relapse with a hazard ratio (HR) of 0.45 (p = 0.007) and death (HR of 0.34, p = 0.005). Cox multivariate analysis indicated that hK11 was an independent prognostic indicator of OS (HR of 0.41, p = 0.025). Kaplan-Meier survival curves further confirmed that women with hK11-positive tumors have longer PFS and OS (p = 0.005 and p = 0.003, respectively). Similarly, in the subgroup of patients with grade 1-2 tumors, hK11-positivity was associated with higher OS in both univariate and multivariate analysis (HR of 0.23 and 0.17, p < 0.05). Finally, in women with optimal debulking after surgery (<1 cm residual tumor), hK11 positivity was associated with a slower disease progression. These results indicate that hK11 is a novel, independent marker of favorable prognosis in patients with ovarian cancer.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12845660

Citation

Borgoño, Carla A., et al. "Favorable Prognostic Value of Tissue Human Kallikrein 11 (hK11) in Patients With Ovarian Carcinoma." International Journal of Cancer, vol. 106, no. 4, 2003, pp. 605-10.
Borgoño CA, Fracchioli S, Yousef GM, et al. Favorable prognostic value of tissue human kallikrein 11 (hK11) in patients with ovarian carcinoma. Int J Cancer. 2003;106(4):605-10.
Borgoño, C. A., Fracchioli, S., Yousef, G. M., Rigault de la Longrais, I. A., Luo, L. Y., Soosaipillai, A., Puopolo, M., Grass, L., Scorilas, A., Diamandis, E. P., & Katsaros, D. (2003). Favorable prognostic value of tissue human kallikrein 11 (hK11) in patients with ovarian carcinoma. International Journal of Cancer, 106(4), 605-10.
Borgoño CA, et al. Favorable Prognostic Value of Tissue Human Kallikrein 11 (hK11) in Patients With Ovarian Carcinoma. Int J Cancer. 2003 Sep 10;106(4):605-10. PubMed PMID: 12845660.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Favorable prognostic value of tissue human kallikrein 11 (hK11) in patients with ovarian carcinoma. AU - Borgoño,Carla A, AU - Fracchioli,Stefano, AU - Yousef,George M, AU - Rigault de la Longrais,Irene A, AU - Luo,Liu-Ying, AU - Soosaipillai,Antoninus, AU - Puopolo,Manuela, AU - Grass,Linda, AU - Scorilas,Andreas, AU - Diamandis,Eleftherios P, AU - Katsaros,Dionyssios, PY - 2003/7/8/pubmed PY - 2003/9/10/medline PY - 2003/7/8/entrez SP - 605 EP - 10 JF - International journal of cancer JO - Int. J. Cancer VL - 106 IS - 4 N2 - Human kallikrein 11 (hK11/trypsin-like serine protease/TLSP, encoded by the KLK11 gene) is a member of the kallikrein family of secreted serine proteases. Recently, we developed a highly sensitive and specific immunoassay for hK11 and found that this protease is expressed in the prostate, stomach and trachea as well as in amniotic fluid and milk of lactating women. Elevated serum hK11 levels were found in 60% of men with prostate cancer and 70% of women with ovarian cancer. Also, hK11 expression was found to be under the regulation of steroid hormones, particularly estrogens, at the level of KLK11 transcription. We hypothesized that hK11 may be implicated in endocrine-related malignancies and serve as a novel prostate and ovarian cancer serological marker. The aim of our study was to examine if hK11 expression in ovarian tumors bears any prognostic significance. The concentration of hK11 (ng per mg of total protein) in 104 ovarian tumor cytosolic extracts was quantified and correlated with clinicopathologic variables and outcome over a median follow-up period of 67 months. Outcome was defined as progression-free survival (PFS) and overall survival (OS). hK11 concentration in ovarian tumor cytosols ranged from 0-21 ng/mg of total protein, with a median of 0.54 ng/mg. An optimal cutoff value of 0.54 ng/mg was selected to categorize tumors as hK11-positive or -negative. hK11-positive tumors were more frequently associated with early stage (Stage I/II) disease, pre-/peri-menopausal status and patients who exhibited complete or partial response to chemotherapy (p < 0.05). Univariate analysis revealed that patients with hK11-positive tumors had a significantly decreased risk of relapse with a hazard ratio (HR) of 0.45 (p = 0.007) and death (HR of 0.34, p = 0.005). Cox multivariate analysis indicated that hK11 was an independent prognostic indicator of OS (HR of 0.41, p = 0.025). Kaplan-Meier survival curves further confirmed that women with hK11-positive tumors have longer PFS and OS (p = 0.005 and p = 0.003, respectively). Similarly, in the subgroup of patients with grade 1-2 tumors, hK11-positivity was associated with higher OS in both univariate and multivariate analysis (HR of 0.23 and 0.17, p < 0.05). Finally, in women with optimal debulking after surgery (<1 cm residual tumor), hK11 positivity was associated with a slower disease progression. These results indicate that hK11 is a novel, independent marker of favorable prognosis in patients with ovarian cancer. SN - 0020-7136 UR - https://www.unboundmedicine.com/medline/citation/12845660/Favorable_prognostic_value_of_tissue_human_kallikrein_11__hK11__in_patients_with_ovarian_carcinoma_ L2 - https://doi.org/10.1002/ijc.11296 DB - PRIME DP - Unbound Medicine ER -