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Clin Cancer Res. 2014 Sep 15;20(18):4904-11. doi: 10.1158/1078-0432.CCR-13-1341. Epub 2014 Mar 31.

SPINK1 protein expression and prostate cancer progression.

Author information

1
Center for Molecular Oncologic Pathology; Departments of Department of Histopathology, St. James's Hospital and Trinity College Dublin Medical School, Dublin, Ireland rflavin@stjames.ie.
2
Channing Division of Network Medicine, Department of Medicine; Department of Epidemiology, Harvard School of Public Health; and.
3
Center for Molecular Oncologic Pathology; Departments of.
4
Center for Molecular Oncologic Pathology; Departments of Department of Histopathology, St. James's Hospital and Trinity College Dublin Medical School, Dublin, Ireland.
5
Radiation Oncology, Dana Farber Cancer Institute;
6
Medical Oncology and.
7
Division of Preventive Medicine, Brigham and Women's Hospital;
8
Center for Molecular Oncologic Pathology; Departments of Medical Oncology and.

Abstract

PURPOSE:

SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer-specific survival.

EXPERIMENTAL DESIGN:

The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983-2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays.

RESULTS:

Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P < 0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant associations between SPINK1 status and Gleason grade or tumor stage. There was no association between SPINK1 expression and biochemical recurrence (P = 0.56). Moreover, there was no association between SPINK1 expression and prostate cancer mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5 years follow-up; HR = 0.71; 95% confidence interval, 0.29-1.76).

CONCLUSIONS:

Our results suggest that SPINK1 protein expression may not be a predictor of recurrence or lethal prostate cancer amongst men treated by radical prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely mutually exclusive, as some previous studies have suggested.

PMID:
24687926
PMCID:
PMC4167171
DOI:
10.1158/1078-0432.CCR-13-1341
[Indexed for MEDLINE]
Free PMC Article
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