Tokunaga Eriko, Yamashita Nami, Kitao Hiroyuki, Tanaka Kimihiro, Taketani Kenji, Inoue Yuka, Saeki Hiroshi, Oki Eiji, Oda Yoshinao, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Breast. 2016 Feb;25:62-8. doi: 10.1016/j.breast.2015.10.006. Epub 2015 Nov 11.
INPP4B is considered to function as a putative tumor suppressor through its inhibitory function of Akt. In various malignant tumors, loss of heterozygosity (LOH) at the chromosomal region containing INPP4B and lower expression of INPP4B has been reported. The purpose of this study was to examine the frequency of the INPP4B LOH and its association with the clinicopathological characteristics and prognosis in breast cancer of Japanese women.
The allelic alteration at the INPP4B and PTEN gene loci was analyzed in 277 invasive primary breast carcinomas. The relationships between INPP4B LOH and the clinicopathological features were investigated.
Among the 238 informative cases for the evaluation, LOH at the INPP4B gene locus was observed in 43 tumors (18.1%). INPP4B LOH was significantly correlated with ER and PR negativity (p = 0.0009 and p = 0.0029, respectively), higher nuclear grade (p < 0.0001), higher Ki67 labeling index (p = 0.0006), triple-negative (TN) subtype (p = 0.0005) and PTEN LOH (p < 0.0001). INPP4B LOH was significantly associated with poorer prognosis, in terms of the relapse-free survival (RFS) and overall survival (OS). According to the multivariate analyses, INPP4B LOH was not independently associated with the prognosis.
The incidence of INPP4B LOH was significantly higher in the TN subtype and positively correlated with PTEN LOH. INPP4B LOH was associated with more aggressive and proliferative phenotype. INPP4B LOH was also associated with poorer prognosis.
INPP4B被认为通过其对Akt的抑制功能发挥潜在肿瘤抑制作用。在各种恶性肿瘤中，已报道在包含INPP4B的染色体区域存在杂合性缺失（LOH）且INPP4B表达降低。本研究的目的是检测日本女性乳腺癌中INPP4B LOH的频率及其与临床病理特征和预后的关系。
对277例浸润性原发性乳腺癌分析INPP4B和PTEN基因位点的等位基因改变。研究INPP4B LOH与临床病理特征之间的关系。
在238例可用于评估的病例中，43例肿瘤（18.1%）观察到INPP4B基因位点的LOH。INPP4B LOH与雌激素受体（ER）和孕激素受体（PR）阴性显著相关（分别为p = 0.0009和p = 0.0029）、核分级较高（p < 0.0001）、Ki67标记指数较高（p = 0.0006）、三阴性（TN）亚型（p = 0.0005）和PTEN LOH（p < 0.0001）。就无复发生存期（RFS）和总生存期（OS）而言，INPP4B LOH与较差的预后显著相关。根据多因素分析，INPP4B LOH与预后无独立相关性。
TN亚型中INPP4B LOH的发生率显著更高，且与PTEN LOH呈正相关。INPP4B LOH与更具侵袭性和增殖性的表型相关。INPP4B LOH也与较差的预后相关。
