title: Profilin-1 expression is associated with high grade and stage and decreased disease-free survival in renal cell carcinoma.
abstract: Clear cell renal cell carcinoma (ccRCC) is associated with high mortality, although individual outcomes are highly variable. Identification of patients with increased risk of disease progression can guide customizing management plan according to disease severity. Profilin-1 (Pfn1) has been recently identified as overexpressed in metastatic ccRCC compared with primary tumors. We examined Pfn1 expression in a tissue microarray of 384 cases of histologically confirmed primary ccRCC with detailed clinical follow-up. Profilin-1 expression showed both cytoplasmic and nuclear staining patterns. The immunoexpression of Pfn1 was scored in a semiquantitative fashion. There was no significant difference in Pfn1 expression between normal kidney and kidney ccRCC. Our results show that strong cytoplasmic Pfn1 expression is associated with high-grade (P < .001) and high-stage (III-IV) (P = .018) disease. Univariate analysis of the data set showed that higher Pfn1 expression is associated with significantly shorter disease-free survival (hazard ratio 7.36, P = .047) and also lower overall survival. Kaplan-Meier analysis showed that high cytoplasmic expression of Pfn1 was also associated with a statistically significant lower disease-free survival (P = .018). It was also associated with lower overall survival, although this was not statistically significant. Profilin-1 lost its prognostic significance in the multivariate analysis when controlling for grade and stage. Profilin-1 expression was not associated with significant prognostic deference in the subgroup of patients with stage 1 disease. Our results suggest that the evaluation of Pfn1 by immunohistochemistry may help to identify patients with an increased risk of disease progression. We validated our results at the messenger RNA level on an independent patient cohort. Higher messenger RNA expression of Pfn1 is associated with significantly lower survival.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8; Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science at the Li KaShing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Karamchandani
authors.affiliation: London Health Sciences, London, Ontario, Canada N6A 5A5.
authors.forename: Manal Y
authors.initials: MY
authors.lastname: Gabril
authors.affiliation: Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science at the Li KaShing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.
authors.forename: Rania
authors.initials: R
authors.lastname: Ibrahim
authors.affiliation: University of Athens, Athens, Greece 106 79.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.affiliation: London Health Sciences, London, Ontario, Canada N6A 5A5.
authors.forename: Emily
authors.initials: E
authors.lastname: Filter
authors.affiliation: Division of Urologic Oncology, Princess Margaret Hospital, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Antonio
authors.initials: A
authors.lastname: Finelli
authors.affiliation: Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1W8.
authors.forename: Jason Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1W8.
authors.forename: Michael
authors.initials: M
authors.lastname: Ordon
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8; Department of Laboratory Medicine, St. Joseph's Health Centre, Toronto, Ontario, Canada M6R 1B5.
authors.forename: Maria
authors.initials: M
authors.lastname: Pasic
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8; Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science at the Li KaShing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Romaschin
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8; Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science at the Li KaShing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada M5B 1T8. Electronic address: yousefg@smh.ca.
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051304:Profilins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495738:PFN1 protein, human; D051304:Profilins; D012333:RNA, Messenger
keywords: Metastasis; Personalized medicine; Pfn1; Profilin; Prognosis; Renal cell carcinoma; Tumor markers