STEAP1 is over-expressed in prostate cancer and prostatic intraepithelial neoplasia lesions, and it is positively associated with Gleason score

Authors and Affiliations:

Inês M Gomes¹, Patrícia Arinto², Carlos Lopes^2,3, Cecília R Santos¹, Cláudio J Maia¹

¹- CICS-UBI- Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal

²- Institute of Biomedical Sciences Abel Salazar, University of Porto, Portugal

³- Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal

^a- Ambos os autores contribuíram de igual forma para o trabalho

Abstract:

Background. STEAP1 is a transmembrane protein of epithelial cells, mostly located at cell-cell junctions, which is  over-expressed on several types of tumors, particularly prostate cancer. Several studies have pointed STEAP1 as a biomarker, but the clinical significance of its over-expression is not fully understood. Therefore, we aimed to establish a relationship between STEAP1 immunoreactivity, and histologic diagnosis or clinical data of patients.

Materials and Methods. Human tissue microarrays were constructed from tissue biopsies of prostate adenocarcinoma (n=63), including non-neoplastic adjacent tissue (n=41), prostatic intraepithelial neoplasia (PIN) lesions (n=7), and 41 prostate samples from patients diagnosed with benign prostatic hyperplasia (BPH). The histologic features of tumor specimens were classified and clinical and pathological data were retrieved. STEAP1 expression was evaluated by immunohistochemical analysis, and semiquatitative quantification was performed using a grade score system based on the intensity and percentage of stained cells.

Results. Over-expression of STEAP1 protein was found in both plasma membrane and cytoplasm of prostate cancer and PIN lesions when compared to non-neoplastic adjacent tissue and BPH samples. Furthermore, its expression associates positively with higher Gleason scores, but not with other clinical data, such as age, PSA levels, pathological stage and metastasis. Regarding its role as a biomarker, STEAP1 is highly liable for distinguishing malignant prostate stages from BPH. On the other hand, it lacks specificity to distinguish PIN lesions from prostate cancer.

Conclusions. STEAP1 is consistently over-expressed in malignant prostate tissue, namely adenocarcinoma and PIN lesions. Its over-expression in PIN lesions and positive association with higher Gleason scores suggests that STEAP1 could be involved on tumor initiation and progression. The high sensitivity and specificity for detection of malignant lesions suggests that STEAP1 may be of clinical usefulness on early disease diagnosis.

Journal:

Urologic Oncology: Seminars and Original Investigations

Link:

http://www.ncbi.nlm.nih.gov/pubmed/24239460