Expression of centromere protein F (CENP-F) associated with higher FDG uptake on PET/CT, detected by cDNA microarray, predicts high-risk patients with primary breast cancer

Shigeto Ueda,Junji Yamamoto,Takayuki Kobayashi,Hidetaka Mochizuki,Jiro Ishida,Nobuo Kondoh,Hitoshi Tsuda,Yoshiyuki Abe,Hideki Asakawa,Mikio Yamamoto,Souhei Yamamoto,Kazuhiko Fukatsu,Katsumi Tamura

doi:10.1186/1471-2407-8-384

Abstract

BackgroundHigher standardized uptake value (SUV) detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) correlates with proliferation of primary breast cancer. The purpose of this study is to identify specific molecules upregulated in primary breast cancers with a high SUV and to examine their clinical significance.MethodsWe compared mRNA expression profiles between 14 tumors with low SUVs and 24 tumors with high SUVs by cDNA microarray. We identified centromere protein F (CENP-F) and CDC6 were upregulated in tumors with high SUVs. RT-PCR and immunohistochemical analyses were performed to validate these data. Clinical implication of CENP-F and CDC6 was examined for 253 archival breast cancers by the tissue microarray.ResultsThe relative ratios of CENP-F and CDC6 expression levels to β-actin were confirmed to be significantly higher in high SUV tumors than in low SUV tumors (p = 0.027 and 0.025, respectively) by RT-PCR. In immunohistochemical analysis of 47 node-negative tumors, the CENP-F expression was significantly higher in the high SUV tumors (74%) than the low SUV tumors (45%) (p = 0.04), but membranous and cytoplasmic CDC6 expressions did not significantly differ between both groups (p = 0.9 each). By the tissue microarray, CENP-F (HR = 2.94) as well as tumor size (HR = 4.49), nodal positivity (HR = 4.1), and Ki67 (HR = 2.05) showed independent impact on the patients' prognosis.ConclusionHigh CENP-F expression, correlated with high SUV, was the prognostic indicators of primary breast cancer. Tumoral SUV levels may serve as a pretherapeutic indicator of aggressiveness of breast cancer.

Highlights

Higher standardized uptake value (SUV) detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) correlates with proliferation of primary breast cancer
Results revealed that the average ratios of centromere protein F (CENP-F) and CDC6 expressions relative to that of β-actin expression were significantly higher in the high SUV group (1.6 ± 0.3 standard error (SE) and 0.9 ± 0.1 SE) than in the low SUV group (0.8 ± 0.3 SE and 0.5 ± 0.1 SE) (p = 0.027 and 0.025, respectively) (Figure 1)
We compared the gene expression profiles between tumors having a high level of SUV and those having a low level of SUV, and we identified 20 candidate genes in high SUV tumors with an mRNA expression level of greater than 1.7-fold that in low SUV tumors by cDNA microarray analysis

Summary

Introduction

Higher standardized uptake value (SUV) detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) correlates with proliferation of primary breast cancer. The purpose of this study is to identify specific molecules upregulated in primary breast cancers with a high SUV and to examine their clinical significance. Primary systemic therapy (PST) is widely practiced as a standard therapy for patients with early-stage breast cancer [3], but it is difficult to preoperatively identify high-risk patients in the PST setting because available information obtained from core needle biopsy specimens is limited. Molecular biology tools such as Oncotype DXTM or the 70-gene expression classifier identified by DNA microarray analysis (MammaPrint®) are going to be used widely for risk evaluation, utility of these tools has not been confirmed with primary breast cancer in the PST setting [4,5,6]. We need new tools that can preoperatively and accurately predict the prognosis of patients with early-stage breast cancer

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