Abstract
BackgroundThe 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.MethodsWe 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 X2 test.ResultsKaplan-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).ConclusionsThe 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.
Highlights
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
We examined the predictive value of the autocrine growth and survival factor GP88/Progranulin in combination with NPI to determine whether adding GP88/Progranulin tumor expression determination to NPI scoring could provide additional prognostic information and further stratify patients in low and high risk recurrence groups within each NPI category
The distribution of NPI scores within the 3 NPI categories (GPG ≤3.4; NPI Medium prognostic group (MPG) 3.4–5.4; NPI Poor prognosis group (PPG) >5.4) provided in Table 1 shows that the patients were fairly evenly distributed among the three NPI categories
Summary
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. In the case of breast cancer patients, the common prognostic factors are tumor size, histological grade, histological nodal status and patient’s age. Estrogen and progesterone receptor and HER-2 expression provide additional information and guideline for treatment decisions Proliferation markers such as DNA ploidy, S fraction or Ki67 expression are increasingly examined and incorporated for risk evaluation at time of diagnosis. Such factors might be used to discriminate among patients at increased risk of recurrence from the ones at low risk and identify patients that may benefit from adjuvant therapy from the ones more likely to display treatment resistance. Some tumor characteristics have been used to define a prognostic index such as the Nottingham prognostic index (NPI) proposed in 1982 [1]
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