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. 2016 May 24;7(21):31029-36.
doi: 10.18632/oncotarget.8829.

MET expression during prostate cancer progression

Esther I Verhoef  1 , Kimberley Kolijn  1 , Maria J De Herdt  2 , Berdine van der Steen  2 , A Marije Hoogland  1 , Hein F B M Sleddens  1 , Leendert H J Looijenga  1 , Geert J L H van Leenders  1
Affiliations

MET expression during prostate cancer progression

Esther I Verhoef et al. Oncotarget. .

Abstract

Tyrosine-kinase inhibitors of the hepatocyte growth factor receptor MET are under investigation for the treatment of hormone-refractory prostate cancer (HRPC) metastasis. Analysis of MET protein expression and genetic alterations might contribute to therapeutic stratification of prostate cancer patients. Our objective was to investigate MET on protein, DNA and RNA level in clinical prostate cancer at various stages of progression. Expression of MET was analyzed in hormone-naive primary prostate cancers (N=481), lymph node (N=40) and bone (N=8) metastases, as well as HRPC (N=54) and bone metastases (N=15). MET protein expression was analyzed by immunohistochemistry (D1C2 C-terminal antibody). MET mRNA levels and MET DNA copy numbers were determined by in situ hybridization. None of the hormone-naive primary prostate cancer or lymph node metastases demonstrated MET protein or mRNA expression. In contrast, MET protein was expressed in 12/52 (23%) evaluable HRPC resections. RNA in situ demonstrated cytoplasmic signals in 14/54 (26%) of the HRPC patients, and was associated with MET protein expression (p=0.025, χ2), in absence of MET amplification or polysomy. MET protein expression was present in 7/8 (88%) hormone-naive and 10/15 (67%) HRPC bone metastases, without association of HRPC (p=0.37; χ2), with MET polysomy in 8/13 (61%) evaluable cases. In conclusion, MET was almost exclusively expressed in HRPC and prostate cancer bone metastasis, but was not related to MET amplification or polysomy. Evaluation of MET status could be relevant for therapeutic stratification of late stage prostate cancer.

Keywords: MET; progression; prostate cancer; protein.

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Conflict of interest statement

The authors have no conflict of interest.

Figures

Figure 1
Figure 1
A. MET protein staining in basal epithelial and endothelial cells (inset), in the normal prostate. B. MET protein absence in localized prostate cancer. C. N-cadherin positive area in localized prostate cancer. D. MET protein absence in the N-cadherin positive area. E. MET RNA expression in normal prostate basal epithelial cells (arrowheads). F. Absence of MET RNA in localized prostate cancer. Scale bars represent 50 μm at 20x (A, C, D) or 40x (B, E, F) magnification.
Figure 2
Figure 2
A. MET protein expression. B. Positive RNA in situ signals (arrowheads). C. FISH did not reveal polysomy or MET amplification (MET red, SE7 green). Scale bars represent 50 μm at 40x (A, B) or 63x (C) magnification.
Figure 3
Figure 3
A. Absence of specific MET protein expression in hormone-naive lymph node metastasis. B. Absence of RNA in situ signals in lymph node metastasis. C. Strong MET protein expression in HRPC bone metastasis. D. Chromosome 7 polysomy in HRPC bone metastasis (MET red, SE7 green). Scale bars represent 50 μm at 40x (A, B, C) or 63x (D) magnification.
See this image and copyright information in PMC

References

    1. Yoshinaga Y, Matsuno Y, Fujita S, Nakamura T, Kikuchi M, Shimosato Y, Hirohashi S. Immunohistochemical detection of hepatocyte growth factor/scatter factor in human cancerous and inflammatory lesions of various organs. Jpn J Cancer Res. 1993;84:1150–1158. - PMC - PubMed
    1. Zarnegar R, DeFrances MC. Expression of HGF-SF in normal and malignant human tissues. EXS. 1993;65:181–199. - PubMed
    1. Hurle RA, Davies G, Parr C, Mason MD, Jenkins SA, Kynaston HG, Jiang WG. Hepatocyte growth factor/scatter factor and prostate cancer: a review. Histol Histopathol. 2005;20:1339–1349. - PubMed
    1. Humphrey PA, Zhu X, Zarnegar R, Swanson PE, Ratliff TL, Vollmer RT, Day ML. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am J Pathol. 1995;147:386–396. - PMC - PubMed
    1. Camp RL, Rimm EB, Rimm DL. Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma. Cancer. 1999;86:2259–2265. - PubMed

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