title: Reevaluating cathepsin D as a biomarker for breast cancer: serum activity levels versus histopathology.
abstract: Cathepsin D is a lysosomal hydrolase involved in intra- and extracellular proteolysis. This enzyme is aberrantly produced and processed in malignancy, and most notably is over-secreted into the tumor cell microenvironment. This hyper-secretion may lead to excessive degradation of the extracellular matrix, and contribute to tumor progression and metastases. These phenomena have been established in vitro, and there is evidence that Cathepsin D is similarly dysregulated in human breast cancer patients. Because breast cancer lacks an effective screening or surveillance biomarker, here we address the hypothesis that serum Cathepsin D activity may be useful to assess the presence or progression of breast cancer in females. While representative histologic sections from various disease-specific cohorts confirm previous findings that increased Cathepsin D production and secretion correlate with tumor progression, we report no difference in serum Cathepsin D activity between patients who are disease free, patients with pre-invasive or limited invasive disease, and patients with metastatic disease. Furthermore, in patients with known metastatic disease, there were no clinical variables associated with significantly different serum Cathepsin D activity. However, the immunohistochemical localization of Cathepsin D expression in histopathologic sections from breast cancer patients correlates with disease progression. Based on the serum results, and in contradistinction to Cathepsin D localization in breast cancer tissues, our findings support using Cathepsin D as a reliable histopathology biomarker for disease progression, but not for serum screening.
authors.affiliation: Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Abbott
authors.forename: Naira V
authors.initials: NV
authors.lastname: Margaryan
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Jeruss
authors.forename: Seema
authors.initials: S
authors.lastname: Khan
authors.forename: Virginia
authors.initials: V
authors.lastname: Kaklamani
authors.forename: David J
authors.initials: DJ
authors.lastname: Winchester
authors.forename: Nora
authors.initials: N
authors.lastname: Hansen
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: Zhila
authors.initials: Z
authors.lastname: Khalkhali-Ellis
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002402:Cathepsin D / Q000378:metabolism*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008247:Lysosomes / Q000201:enzymology; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D002402:Cathepsin D