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SPINK1 Overexpression in Localized Prostate Cancer: a Rare Event Inversely Associated with ERG Expression and Exclusive of Homozygous PTEN Deletion

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Pathology & Oncology Research

Abstract

SPINK1 is proposed as potential prognostic marker in prostate cancer (PCA). However, its relation to PTEN and ERG in localized PCA remains unclear. The study population consisted of two independent cohorts of men treated by radical prostatectomy for localized PCA (discovery n = 218 and validation n = 129). Patterns of association between SPINK1 and each of ERG and PTEN were evaluated by immunohistochemistry and fluorescence in situ hybridization. Associations between SPINK1 expression and various pathologic parameters and clinical outcome were also investigated. SPINK1 was expressed in 15.3 % and 10.9 % of cases in the discovery and validation cohort, respectively. SPINK expression was observed in 5.56 % of high-grade prostatic intraepithelial neoplasia and 1.1 % of adjacent morphologically benign prostatic glands. SPINK1 and ERG expression were almost exclusive, with only 1.0 % of the cases co-expressing both in the same core sample. SPINK1 interfocal and within-core heterogeneity was noted in 29.2 % and 64.6 % of cases, respectively. SPINK1 expression was not significantly associated with PTEN deletion in the two cohorts (p = 0.871 for discovery cohort and p = 0.293 for validation cohort). While SPINK1 expression did occur with hemizygous PTEN deletion, there was a complete absence of SPINK1 expression in PCA showing homozygous PTEN deletion, which was confirmed in the validation cohort (p = 0.02). Despite SPINK1’s association with higher Gleason score (>7) (p = 0.02), it was not associated with other pathological parameters or biochemical recurrence post-radical prostatectomy. We documented absolute exclusivity between SPINK1 overexpression and homozygous PTEN deletion in localized PCA. SPINK1 and ERG expressions are exclusive events in PCA. SPINK1 is not of added prognostic value in localized PCA.

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Abbreviations

BAC:

Bacterial artificial chromosome

CRPC:

Castrate resistant prostate cancer

DAB:

3,3′-Diaminobenzidine (DAB)

ERG:

ETS-related gene

FISH:

Fluorescence in-situ hybridization

GS(s):

Gleason score(s)

H&E:

Haematoxylin and eosin

HGPIN(s):

High-grade prostatic intraepithelial neoplasia(s)

IHC:

Immunohistochemistry

KDal:

Kilodalton

PCA(s):

Prostate cancer(s)

PSA:

Prostate-specific antigen

PSTI:

Pancreatic secretory trypsin inhibitor

PTEN:

Phosphatase and tensin homolog

SD:

Standard deviations

SPINK1:

Serine protease inhibitor Kazal-type 1

TATI:

Tumour-associated trypsin inhibitor

TMA:

Tissue microarray

TMPRSS2:

Transmembrane protease, serine 2

UHN:

University Health Network

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Acknowledgment

This work was supported in part by the Prostate Cancer Foundation Young Investigator Award (T.A.B). This work was also supported by Prostate cancer Canada and is proudly funded by the Movember Foundation-Grant #B2013-01.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, 7007, 14sth st sw, Calgary, AB, T2V 1P9, Canada

    Kuo-Cheng Huang & Tarek A. Bismar

  2. Department of Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, ON, Canada

    Andrew Evans

  3. Department of Urology, University of Calgary, Calgary, AB, Canada

    Bryan Donnelly

  4. Departments of Oncology, Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada

    Tarek A. Bismar

  5. Southern Alberta Cancer Institute and Tom Baker Cancer Center, Calgary, AB, Canada

    Tarek A. Bismar

  6. The Prostate Cancer Center, Calgary, AB, Canada

    Bryan Donnelly & Tarek A. Bismar

Authors
  1. Kuo-Cheng Huang
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  2. Andrew Evans
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  4. Tarek A. Bismar
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Correspondence to Tarek A. Bismar.

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The authors have no conflict of interest to declare in this study.

Electronic supplementary material

Supplementary figure 1

PTEN genomic deletions using four-colour interphase FISH strategy. A. Wild type PTEN; B. Hemizygous deletions and C. Homozygous deletion (GIF 299 kb)

High resolution image (TIFF 711 kb)

Supplementary figure 2

Morphologically benign gland showing SPINK1 expression on IHC (original magnification 200×) (GIF 670 kb)

High resolution image (TIFF 1815 kb)

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Huang, KC., Evans, A., Donnelly, B. et al. SPINK1 Overexpression in Localized Prostate Cancer: a Rare Event Inversely Associated with ERG Expression and Exclusive of Homozygous PTEN Deletion. Pathol. Oncol. Res. 23, 399–407 (2017). https://doi.org/10.1007/s12253-016-0119-9

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  • DOI: https://doi.org/10.1007/s12253-016-0119-9

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