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Cathepsin D Expression in Colorectal Cancer: From Proteomic Discovery through Validation Using Western Blotting, Immunohistochemistry, and Tissue Microarrays.

Kirana C, Shi H, Laing E, Hood K, Miller R, Bethwaite P, Keating J, Jordan TW, Hayes M, Stubbs R - Int J Proteomics (2012)

Bottom Line: Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC) remains disappointing with some 40-50% of newly diagnosed patients ultimately dying of metastatic disease.Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy.Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival.

View Article: PubMed Central - PubMed

Affiliation: Wakefield Biomedical Research Unit, University of Otago, Wellington 6242, New Zealand.

ABSTRACT
Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC) remains disappointing with some 40-50% of newly diagnosed patients ultimately dying of metastatic disease. Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy. We have identified that cathepsin D expression was significantly greater in cells from invasive front (IF) area and liver metastasis (LM) than those from main tumour body (MTB). Cathepsin D expression was subsequently examined by immunohistochemistry in tissue microarrays from 119 patients with CRC. Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival. However, cathepsin D expression in cells from the MTB was highly elevated in late stage CRC and showed significant correlation with subsequent distant metastasis and shorter cancer-specific survival. We also found that macrophages surrounding tumour cells stained strongly for cathepsin D but there was no significant correlation found between cathepsin D in macrophages at IF and MTB of CRC patient with the clinic-pathological parameters examined.

No MeSH data available.


Related in: MedlinePlus

Validation of cathepsin D expression at two different regions, main tumor body. (MTB) and invasive front (IF) area of primary tumor and liver metastasis (LM) from the same patient by immunohistochemistry (IHC) (DAB substrate, brown). Sections were counterstained with haematoxylin (blue) (20x objective).
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fig2: Validation of cathepsin D expression at two different regions, main tumor body. (MTB) and invasive front (IF) area of primary tumor and liver metastasis (LM) from the same patient by immunohistochemistry (IHC) (DAB substrate, brown). Sections were counterstained with haematoxylin (blue) (20x objective).

Mentions: Cathepsin D was found to have different expressions in three different areas of interest of colorectal tumor tissues in our discovery project. Expression of cathepsin D in tumor cells at the IF and in LM was significantly higher than that in the MTB when profiled using 2 D-DIGE (Figure 1(a)). The gel spot position and concentration of cathepsin D in these three areas of tumor were validated with 2DE western blotting (Figure 1(b)). Validation by IHC also confirmed relatively greater abundance of cathepsin D at the IF and in LM compared to MTB in 9 of 11 (82%) CRC patients. IHC images from a representative set of tissues from the same patient are presented in Figure 2.


Cathepsin D Expression in Colorectal Cancer: From Proteomic Discovery through Validation Using Western Blotting, Immunohistochemistry, and Tissue Microarrays.

Kirana C, Shi H, Laing E, Hood K, Miller R, Bethwaite P, Keating J, Jordan TW, Hayes M, Stubbs R - Int J Proteomics (2012)

Validation of cathepsin D expression at two different regions, main tumor body. (MTB) and invasive front (IF) area of primary tumor and liver metastasis (LM) from the same patient by immunohistochemistry (IHC) (DAB substrate, brown). Sections were counterstained with haematoxylin (blue) (20x objective).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3420108&req=5

fig2: Validation of cathepsin D expression at two different regions, main tumor body. (MTB) and invasive front (IF) area of primary tumor and liver metastasis (LM) from the same patient by immunohistochemistry (IHC) (DAB substrate, brown). Sections were counterstained with haematoxylin (blue) (20x objective).
Mentions: Cathepsin D was found to have different expressions in three different areas of interest of colorectal tumor tissues in our discovery project. Expression of cathepsin D in tumor cells at the IF and in LM was significantly higher than that in the MTB when profiled using 2 D-DIGE (Figure 1(a)). The gel spot position and concentration of cathepsin D in these three areas of tumor were validated with 2DE western blotting (Figure 1(b)). Validation by IHC also confirmed relatively greater abundance of cathepsin D at the IF and in LM compared to MTB in 9 of 11 (82%) CRC patients. IHC images from a representative set of tissues from the same patient are presented in Figure 2.

Bottom Line: Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC) remains disappointing with some 40-50% of newly diagnosed patients ultimately dying of metastatic disease.Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy.Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival.

View Article: PubMed Central - PubMed

Affiliation: Wakefield Biomedical Research Unit, University of Otago, Wellington 6242, New Zealand.

ABSTRACT
Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC) remains disappointing with some 40-50% of newly diagnosed patients ultimately dying of metastatic disease. Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy. We have identified that cathepsin D expression was significantly greater in cells from invasive front (IF) area and liver metastasis (LM) than those from main tumour body (MTB). Cathepsin D expression was subsequently examined by immunohistochemistry in tissue microarrays from 119 patients with CRC. Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival. However, cathepsin D expression in cells from the MTB was highly elevated in late stage CRC and showed significant correlation with subsequent distant metastasis and shorter cancer-specific survival. We also found that macrophages surrounding tumour cells stained strongly for cathepsin D but there was no significant correlation found between cathepsin D in macrophages at IF and MTB of CRC patient with the clinic-pathological parameters examined.

No MeSH data available.


Related in: MedlinePlus