HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Differential cellular localization of CELSR2 and ING4 and correlations with hormone receptor status in breast cancer

Liejun Jiang1*, Xiliu Zhang2*, Chenglin Xiang3, Joseph Geradts4#, Qiang Wei5, Yuanzi Liang6, Huayi Huang1,7 and Jun-Fa Xu6

1Department of Laboratory Medicine, the People's Hospital of Guangxi Zhuang Autonomous Region, 2Department of Pathology, the First Affiliated Hospital of Guangxi Traditional Chinese Medicine, Nanning, Guangxi, 3Department of Pathology, Huayin Medical Laboratory, Guangzhou, Guangdong, China, 4Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA, 5Department of Pathology, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China, 6Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, Guangdong, China and 7Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA
#Present address: Multi-Scale Translational Research Core Laboratory, Department of Population Sciences, City of Hope National Medical Center, Duarte, California, USA
*These authors contributed equally to this work

Offprint requests to: Huayi Huang, PhD, Department of Laboratory Medicine, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China and Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA. e-mail: Huayi.Huang@Roswellpark.org or Junfa Xu, MD, PhD, Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, Guangdong, China. e-mail: imxujunfa@163.com


Summary. CELSR2 is postulated to be a receptor involved in contact-mediated communication; however, its expression and function in cancer remain unknown. ING4 is a tumor suppresor encoded by the ING4 gene which inhibits cell growth. The expression of CELSR2 and ING4 in breast tumors and in benign epithelial cells have been analyzed and correlated with HER2, ER, and PR status. Immunohistochemistry was used to analyze the expression of CELSR2 and ING4 protein in breast tumors and benign epithelial cells. The differential cellular localization of both markers was analyzed and results were also correlated with HER2, ER, and PR status. CELSR2 and ING4 cytoplasmic expression was significantly stronger in tumors than in benign epithelial cells, while the nuclear expression of both markers was significantly stronger in benign epithelial cells than in tumors. When comparing the two markers in the same type of tissues, the nuclear expression of CELSR2 was significantly stronger than cytoplasmic in benign epithelial cells, while there was no significant difference in the cellular localization of CELSR2 in tumors. For ING4, the cytoplasmic expression was significantly stronger than nuclear expression in tumors, while in benign epithelial cells, ING4 was expressed at similar levels in both compartments. There was no correlation between CELSR2 expression and HER2, ER, and PR status in tumors. However, the cytoplasmic expression of ING4 was associated with HER2 positivity in tumors. Both CELSR2 and ING4 display increased cytoplasmic staining in breast cancer cells compared to benign epithelium, suggesting a possible role of both genes in the pathogenesis of human mammary neoplasia. Histol Histopathol 33, 835-842 (2018)

Key words: Cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2), Inhibitor of growth 4 (ING4), Human epidermal growth factor receptor 2 (HER2), Breast cancer, Metastasis

DOI: 10.14670/HH-11-979