Loss of heterozygosity in thyroid hormone receptor beta in invasive breast cancer



Loss of heterozygosity (LOH) on chromosome arm 3p, where the gene of thyroid hormone receptor beta (THRB) is located, has been reported in breast cancer. Although some studies performed in vitro have suggested that THRB could act as a tumor suppressor in breast cancer development, there is still no unequivocal evidence to support this.


To determine the role of LOH in breast tumor development, the LOH of THRB and its proximal microsatellite markers D3S1293, D3S3659, D3S3700, D3S2307 and D3S2336 was investigated in a genomic region spanning ~3.3 Mb in tumor specimens and in corresponding normal tissues of 74 invasive breast cancer patients. The association was analyzed between LOH in microsatellite markers and clinicopathological characteristics.


LOH was detected in D3S1293 (36.7%), THRB (59.4%), D3S3659 (37.5%) and D3S3700 (55.2%) among the informative cases, while LOH was not detected in D3S2307 and D3S2336. Cases exhibited LOH of 52.8%-71.4% if any 2 markers were combined and analyzed out of the first 4 microsatellite markers. LOH in THRB was associated with negative estrogen receptor (ER), negative progesterone receptor (PR), both negative estrogen receptor and progesterone receptor (HR) and human epidermal growth factor receptor-2 (HER2) and lymph node metastasis (p = 0.0001, p = 0.005, p = 0.001 and p = 0.018). The association with negative PR in LOH in THRB and/or D3S1293 was pronounced (p<0.0001). LOH in D3S3700 showed an association with lymph node metastasis (p = 0.014). This association was enhanced if D3S3700 was combined with THRB or D3S3659 (p = 0.0004, p = 0.0002).


LOH in THRB and its proximal microsatellite markers may play a role in tumorigenesis and development in invasive breast cancer.

Tumori 2015; 101(5): 572 - 577




Yaqin Ling, Qing Li, Hui Yang, Yonghe Wang, Fabing Tang, Hongfei Kang, Yong Wang

Article History


Financial support: This work was funded by Gansu International Science and Technology Cooperation Program (1011WCGA166).
Conflict of interest: The authors declared that they have no conflicts of interest to this work.

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  • Institute of Pathophysiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou - PR China
  • Department of Gynecology and Obstetrics, Second People’s Hospital of Lanzhou City, Lanzhou - PR China
  • First Medical Department, Qingshui County People’s Hospital, Qingshui County, Tianshui City - PR China
  • Department of Pathology, First Hospital of Lanzhou University, Lanzhou - PR China
  • Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou - PR China
  • Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, Gansu - PR China

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