title: Evaluation and prognostic significance of human tissue kallikrein-related peptidase 6 (KLK6) in colorectal cancer.
abstract: The prognosis of patients with colorectal cancer (CRC) is assessed through conventional clinicopathological parameters, which are not always accurate. Members of the human kallikrein-related peptidases gene family represent potential cancer biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 6 (KLK6) by immunohistochemistry in CRC to correlate this expression with various histopathological and clinical variables, and to evaluate its significance as a predictor of disease outcome. KLK6 expression was evaluated by immunohistochemistry and an expression score was calculated for each case. In CRC, KLK6 expression was decreased compared to normal colonic mucosa. A statistically significant, positive association was observed between KLK6 and tumor stage (p=0.036), lymph node metastases (p=0.030), and liver metastases (p=0.025). Univariate analysis showed that KLK6 expression and stage had statistically significant correlation with disease-free survival (p=0.045 and p<0.001, respectively) and overall survival (p=0.027 and p<0.001, respectively). Cox multivariate analysis showed that KLK6 expression was an independent predictor of unfavorable overall survival (p=0.041). Kaplan-Meier survival curves showed that KLK6-positive patients have statistically significant lower disease-free and overall survival. In conclusion, KLK6 immunostaining is an independent prognostic marker in patients with CRC.
authors.affiliation: Department of Pathology, Metropolitan Hospital, Athens, Greece.
authors.forename: Constantina
authors.initials: C
authors.lastname: Petraki
authors.forename: William
authors.initials: W
authors.lastname: Dubinski
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Carol
authors.initials: C
authors.lastname: Saleh
authors.forename: Maria D
authors.initials: MD
authors.lastname: Pasic
authors.forename: Vassilios
authors.initials: V
authors.lastname: Komborozos
authors.forename: Bishoy
authors.initials: B
authors.lastname: Khalil
authors.forename: Manal Y
authors.initials: MY
authors.lastname: Gabril
authors.forename: Catherine
authors.initials: C
authors.lastname: Streutker
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006115:Greece; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C103551:KLK6 protein, human; D007610:Kallikreins