title: Determination of GP88 (progranulin) expression in breast tumor biopsies improves the risk predictive value of the Nottingham Prognostic Index.
abstract: BACKGROUND
  The Nottingham Prognostic Index (NPI), which combines numerical values for nodal status, tumor size and histological grade, is used in the standard of care to provide predictive value information on post-surgery survival for patients with primary breast cancer. Attempts to improve the performance of the NPI algorithm have been carried out by testing the inclusion of other biomarker expression and morphological features such as vascular invasion. In the present study, we investigated whether expression of the autocrine growth and survival factor GP88 (progranulin), known to be overexpressed in breast cancer, would improve NPI's predictive value.
  
  
  METHODS
  We examined by immunohistochemistry (IHC) the GP88 expression in 508 cases of estrogen receptor positive invasive ductal carcinoma with known clinical outcomes and for which NPI had been determined. GP88 IHC expression was scored by two board certified pathologists and classified into two score groups of GP88 <3+ (0, 1+, 2+) and GP88 = 3+. The correlation between GP88 scoring, NPI and disease-free (DFS) or overall survival (OS) outcomes was then examined by Kaplan-Meier analysis, Cox proportional Hazard (CPH) ratio and Pearson's X (2) test.
  
  
  RESULTS
  Kaplan-Meier survival graphs of cases categorized by their NPI scores (<3.4, 3.4-5.4, >5.4) and GP88 expression showed that for patients within the same NPI subgroup, patients having tumors with a high GP88 expression (GP88 IHC score of 3+) had a worse DFS than patients with tumors that had a low GP88 expression (GP88 IHC score <3+). When adjusted for NPI, high GP88 score was significantly associated with recurrence with a hazard ratio of 3.30 (95 % CI 2.12 to 5.14).
  
  
  CONCLUSIONS
  The data suggest that the determination of GP88 tumor expression at time of diagnosis for early stage breast cancer patients can provide additional survival information to that provided by NPI alone and thus may be useful for risk management of patients diagnosed with breast cancer.
authors: A&G Pharmaceutical Inc., Columbia, MD, USA. gserrero@agpharma.com.|Program of Oncology, University Maryland Greenebaum Cancer Center, Baltimore, MD, USA. gserrero@agpharma.com.
authors: Ginette
authors: http://orcid.org/0000-0003-3607-0273
authors: G
authors: Serrero
authors: School of Statistics, University of Minnesota, Minneapolis, MN, USA.
authors: Douglas M
authors: DM
authors: Hawkins
authors: Cleveland Clinic Florida, Weston, FL, USA.
authors: Pablo A
authors: PA
authors: Bejarano
authors: Program of Oncology, University Maryland Greenebaum Cancer Center, Baltimore, MD, USA.
authors: Olga
authors: O
authors: Ioffe
authors: Program of Oncology, University Maryland Greenebaum Cancer Center, Baltimore, MD, USA.
authors: Katherine R
authors: KR
authors: Tkaczuk
authors: Elliot, Elliot, Head Breast Cancer Research & Treatment Center, Baton Rouge, LA, USA.
authors: Robert E
authors: RE
authors: Elliott
authors: Elliot, Elliot, Head Breast Cancer Research & Treatment Center, Baton Rouge, LA, USA.
authors: Jonathan F
authors: JF
authors: Head
authors: Elliot, Elliot, Head Breast Cancer Research & Treatment Center, Baton Rouge, LA, USA.
authors: Jeffrey
authors: J
authors: Phillips
authors: University of Kansas Medical Center, Kansas City, KS, USA.
authors: Andrew K
authors: AK
authors: Godwin
authors: University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors: JoEllen
authors: J
authors: Weaver
authors: A&G Pharmaceutical Inc., Columbia, MD, USA.
authors: David
authors: D
authors: Hicks
authors: A&G Pharmaceutical Inc., Columbia, MD, USA.
authors: Binbin
authors: B
authors: Yue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D000077153:Progranulins; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D011960:Receptors, Estrogen
keywords: Biomarker; Breast Cancer; GP88; Immunohistochemistry; Nottingham Prognostic Index; Prognostic; Progranulin