title: Human kallikrein 6: a new potential serum biomarker for uterine serous papillary cancer.
abstract: OBJECTIVE
  The discovery of novel biomarkers might greatly contribute to improve clinical management and outcomes in uterine serous papillary carcinoma (USPC), a highly aggressive variant of endometrial cancer.
  
  
  METHODS
  Human kallikrein 6 (hK6) gene expression levels were evaluated in 29 snap-frozen endometrial biopsies, including 13 USPC, 13 endometrioid carcinomas, and 3 normal endometrial cells by real-time PCR. Secretion of hK6 protein by 14 tumor cultures, including 3 USPC, 3 endometrioid carcinoma, 5 ovarian serous papillary carcinoma, and 3 cervical cancers, was measured using a sensitive ELISA. Finally, hK6 concentration in 79 serum and plasma samples from 22 healthy women, 20 women with benign diseases, 20 women with endometrioid carcinoma, and 17 USPC patients was studied.
  
  
  RESULTS
  hK6 gene expression levels were significantly higher in USPC when compared with endometrioid carcinoma (mean copy number by real-time PCR, 1,927 versus 239, USPC versus endometrioid carcinoma; P < 0.01). In vitro hK6 secretion was detected in all primary USPC cell lines tested (mean, 11.5 microg/L) and the secretion levels were similar to those found in primary ovarian serous papillary carcinoma cultures (mean, 9.6 microg/L). In contrast, no hK6 secretion was detectable in primary endometrioid carcinoma and cervical cancer cultures. hK6 serum and plasma concentrations (mean +/- SE) among normal healthy females (2.7 +/- 0.2 microg/L), patients with benign diseases (2.4 +/- 0.2 microg/L), and patients with endometrioid carcinoma (2.6 +/- 0.2 microg/L) were not significantly different. In contrast, serum and plasma hK6 values in USPC patients (6.1 +/- 1.1) were significantly higher than those in the noncancer group (P = 0.006), benign group (P = 0.003), and endometrioid carcinoma patients (P = 0.005).
  
  
  CONCLUSIONS
  hK6 is highly expressed in USPC and is released in the plasma and serum of USPC patients. hK6 may represent a novel biomarker for USPC for monitoring early disease recurrence and response to therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7199, USA. santinalessandrod@uams.edu
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Stefania
authors.initials: S
authors.lastname: Bellone
authors.forename: Antoninus
authors.initials: A
authors.lastname: Soosaipillai
authors.forename: Stefania
authors.initials: S
authors.lastname: Cane
authors.forename: Michela
authors.initials: M
authors.lastname: Palmieri
authors.forename: Alexander
authors.initials: A
authors.lastname: Burnett
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Roman
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000097:blood / Q000235:genetics / Q000473:pathology; D018283:Cystadenocarcinoma, Papillary / Q000097:blood / Q000235:genetics / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000235:genetics / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C103551:KLK6 protein, human; D007610:Kallikreins