Mass spectrometry–based assessment of prostate cancer–associated crystalloids reveals enrichment for growth and differentiation factor 15

Burak Tekin, Surendra Dasari, Jason D. Theis, Julie A. Vrana, David L. Murray, Devin Oglesbee, R. Houston Thompson, Bradley C. Leibovich, Stephen A. Boorjian, Rumeal D. Whaley, Loren Herrera Hernandez, Rafael E. Jimenez, John C. Cheville, R. Jeffrey Karnes, William R. Sukov, Sounak Gupta

Research output: Contribution to journalArticlepeer-review


Intraluminal crystalloids are a common finding within malignant prostatic acini and are infrequently identified within benign glands. The proteomic composition of these crystalloids remains poorly understood and may provide insight regarding prostate cancer pathogenesis. Laser microdissection–assisted liquid chromatography–tandem mass spectrometry (LMD-LC-MS/MS) was performed to compare proteomic composition of corpora amylacea within benign acini (n = 9), prostatic adenocarcinoma–associated crystalloids (n = 8), benign (n = 8), and malignant prostatic acini (n = 6). The expression of candidate biomarkers was then measured in urine specimens from patients with (n = 8) and without prostate cancer (n = 10) using ELISA, and immunohistochemistry-based expression in adjacent prostate cancer and benign glands was assessed in 56 whole-slide sections from radical prostatectomy specimens. LMD-LC-MS/MS revealed enrichment for the C-terminal portion of growth and differentiation factor 15 (GDF15) in prostatic crystalloids. Although urinary GDF15 levels were higher in patients with prostatic adenocarcinoma compared to those without (median: 1561.2 versus 1101.3, arbitrary units), this did not meet statistical significance (P = 0.07). Immunohistochemistry for GDF15 revealed occasional positivity in benign glands (median H-score: 30, n = 56), and diffuse positivity in prostatic adenocarcinoma (median H-score: 200, n = 56, P < 0.0001). No significant difference was identified within different prognostic grade groups of prostatic adenocarcinoma, or within malignant glands with large cribriform morphology. Our results show that the C-terminal portion of GDF15 is enriched in prostate cancer–associated crystalloids, and higher GDF15 expression is seen in malignant rather than benign prostatic acini. Improved understanding of the proteomic composition of prostate cancer–associated crystalloids provides the rationale for evaluating GDF15 as a urine-based biomarker of prostate cancer.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalHuman Pathology
StatePublished - May 2023


  • GDF15
  • Growth and differentiation factor 15
  • MIC1
  • Prostate cancer
  • Prostate crystalloid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


Dive into the research topics of 'Mass spectrometry–based assessment of prostate cancer–associated crystalloids reveals enrichment for growth and differentiation factor 15'. Together they form a unique fingerprint.

Cite this