Molecular and Cellular Pathology

BJC Open article

British Journal of Cancer (2002) 87, 763–771. doi:10.1038/sj.bjc.6600533 www.bjcancer.com
Published online 23 September 2002

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

B R Hoffman1,2, D Katsaros3, A Scorilas4, P Diamandis1, S Fracchioli3, I A Rigault de la Longrais3, T Colgan1,2, M Puopolo3, G Giardina5, M Massobrio3 and E P Diamandis1,2

  1. 1Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada
  2. 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5G 1L5, Canada
  3. 3Department of Gynecology, Gynecologic Oncology Unit, University of Turin, Turin, Italy 10126
  4. 4National Center of Scientific Research ‘Demokritos’, IPC, Athens, 153 10 Greece
  5. 5Department of Breast and Gynecologic Oncology, S. Anna Hospital, Turin, Italy 10126

Correspondence: E P Diamandis, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5; E-mail: ediamandis@mtsinai.on.ca

Received 17 April 2002; Accepted 25 June 2002

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Abstract

Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (nghK6mg−1 total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (>35ng hK6mg−1 total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (nghK6mg−1 total protein) was higher in late stage disease, serous histotype, residual tumour >1cm and suboptimal debulking (>1cm) (P<0.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis.

Keywords:

kallikrein 6; prognosis; ovarian cancer; survival; biomarker