Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer

Eriko Tokunaga; Nami Yamashita; Hiroyuki Kitao; Kimihiro Tanaka; Kenji Taketani; Yuka Inoue; Hiroshi Saeki; Eiji Oki; Yoshinao Oda; Yoshihiko Maehara

doi:10.1016/j.breast.2015.10.006

Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer

Breast. 2016 Feb:25:62-8. doi: 10.1016/j.breast.2015.10.006. Epub 2015 Nov 11.

Authors

Affiliations

¹ 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. Electronic address: eriko@surg2.med.kyuhsu-u.ac.jp.
² Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
³ Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁴ Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

PMID: 26577950
DOI: 10.1016/j.breast.2015.10.006

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Breast cancer; INPP4B; Loss of heterozygosity; PTEN; Triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / chemistry
Breast Neoplasms / genetics*
Carcinoma, Ductal, Breast / chemistry
Carcinoma, Ductal, Breast / genetics*
Female
Genes, Tumor Suppressor
Humans
Japan
Ki-67 Antigen / analysis
Loss of Heterozygosity / genetics*
Middle Aged
PTEN Phosphohydrolase / genetics
Phenotype
Phosphoric Monoester Hydrolases / genetics*
Prognosis
Receptors, Estrogen / analysis
Receptors, Progesterone / analysis
Triple Negative Breast Neoplasms / genetics*

Substances

Ki-67 Antigen
Receptors, Estrogen
Receptors, Progesterone
Phosphoric Monoester Hydrolases
phosphatidylinositol-3,4-bisphosphate 4-phosphatase
PTEN Phosphohydrolase
PTEN protein, human