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SPINK1 protein expression and prostate cancer progression
Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, USA; Departments of Medical Oncology, Dana Farber Cancer Institute, USA.
Channing Division of Network Medicine, Department of Medicine, USA; Department of Epidemiology, Harvard School of Public Health, USA.
Channing Division of Network Medicine, Department of Medicine, USA; Department of Epidemiology, Harvard School of Public Health, USA.
Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, USA.
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2014 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 20, no 18, 4904-11 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Philadelphia, USA: American Association for Cancer Research , 2014. Vol. 20, no 18, 4904-11 p.
National Category
Medical and Health Sciences Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-41406DOI: 10.1158/1078-0432.CCR-13-1341ISI: 000342358500019PubMedID: 24687926Scopus ID: 2-s2.0-84907431664OAI: oai:DiVA.org:oru-41406DiVA: diva2:811710
Available from: 2015-05-12 Created: 2015-01-14 Last updated: 2017-10-17Bibliographically approved

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