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


METHODS
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.


RESULTS
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&lt;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).


CONCLUSIONS
LOH in THRB and its proximal microsatellite markers may play a role in tumorigenesis and development in invasive breast cancer.
Institute of Pathophysiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou - PR China.
Yaqin
Y
Ling
Institute of Pathophysiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou - PR China.
Qing
Q
Li
Department of Gynecology and Obstetrics, Second People's Hospital of Lanzhou City, Lanzhou - PR China.
Hui
H
Yang
First Medical Department, Qingshui County People's Hospital, Qingshui County, Tianshui City - PR China.
Yonghe
Y
Wang
Department of Pathology, First Hospital of Lanzhou University, Lanzhou - PR China.
Fabing
F
Tang
Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou - PR China.
Hongfei
H
Kang
Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, Gansu - PR China.
Yong
Y
Wang
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics*; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D037042:Thyroid Hormone Receptors beta; C508053:ERBB2 protein, human