Elsevier

Human Pathology

Volume 35, Issue 11, November 2004, Pages 1385-1391
Human Pathology

Original contributions
Dysregulated expression of S100A11 (calgizzarin) in prostate cancer and precursor lesions

https://doi.org/10.1016/j.humpath.2004.07.015Get rights and content

Abstract

S100A11 is a calcium-binding protein implicated in a variety of biologic functions such as proliferation and differentiation as well as in cancer. To further understand its role in prostate cancer, we performed immunohistochemistry on a series of benign, premalignant, malignant and metastatic prostate cancer tissues in addition to prostate cancer derived cell lines. In benign prostatic hyperplasia (n = 30) and benign tissue adjacent to adenocarcinoma (n = 54), S100A11 expression was significantly higher in basal cells compared with in luminal cells (P < 0.001). A complete absence of staining was seen in 4/14 (29%) lesions of prostatic intraepithelial neoplasia. The majority of tumors, 39/54 (72%), showed significant overexpression of S100A11 compared with the luminal cells of adjacent benign epithelium (P < 0.001), whereas 14/54 (26%) of cases showed an absence of staining. All 4 cases of metastatic cancer showed intense to moderate expression. There was a significant association between S100A11 expression and high pathologic stage (pT3b) versus lower stages (pT2a-3a; P = 0.027), but not with tumor Gleason score or prostate-specific antigen levels. LNCaP, PC3, and Du145 cancer cell lines showed intense to moderate S100A11 expression by immunochemistry, which was confirmed by Western blotting and reverse-transcription polymerase chain reaction. A survey of 14 other types of normal tissues arranged on a tissue microarray showed that S100A11 is widely expressed amongst epithelia. Our finding of frequent dysregulated expression of S100A11 in cancer and precursor lesions, together with an association with high histological stage, suggests that S100A11 may be involved in prostate cancer development and progression.

Section snippets

Patients and prostate tissue

Prostate tissue from 88 patients attending 2 centers (Academic Urology Unit, University of Sheffield and CeRePP-EA3104, Université Paris 7), were used after full informed consent and local ethics committee approval. These comprised 30 paraffin-embedded cases of benign prostatic hyperplasia (BPH), which were obtained by transurethral resection of prostate, and 54 cases of prostatic adenocarcinoma with matching adjacent benign epithelium, which were obtained either by radical prostatectomy or

Specificity of the anti-S100A11 antibody

The specificity of the guinea pig anti-S100A11 antibody has been reported previously and has been shown to be highly reactive against human recombinant S100A11 but unreactive against recombinant S100A1, S100B, or S100A6 proteins.24 Western blot analysis of prostate cancer cell lines, LNCaP, Du145, and PC3 showed the presence of a band at the expected size of ∼10 KDa, which corresponded to the band seen by using recombinant S100A11 protein (Fig 2). Preimmune guinea-pig serum used as a negative

Discussion

By using immunohistochemistry, we have shown that in benign prostate epithelium, significantly higher expression of S100A11 occurs within the basal cells compared with the adjacent luminal cells. The relationship between basal and luminal cells in prostatic epithelium is poorly understood.26 One hypothesis proposes that the terminally differentiated luminal cells are derived from the basal cell layer via a process involving cell division and differentiation, whereas another suggests that basal

Acknowledgements

The authors thank Dr Sabapathy Balasubramanian for advice and help with the statistical analysis.

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    I.R. is supported by an NCRI Collaborative grant to FCH (MRC 58152).

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