Dysplastic nodules with glypican-3 positive immunostaining: a risk for early hepatocellular carcinoma.
Glypican-3 (GPC3) has been reported to be a novel serum and histochemical marker for HCC. The positivity or negativity for GPC3 in hepatic precancerous lesions, such as dysplastic nodules (DN), has also been described. Moreover, our previous studies have demonstrated that some DN in liver cirrhosis represent monoclonal hyperplasia, and confirmed their neoplastic nature. However, additional studies must be performed to investigate further the relationship between DN with GPC3 positivity and HCC. Thus, we first investigated the expression of GPC3 in 136 HCC and 103 small DN (less than 1 cm in diameter) by immunohistochemical staining and determined the clonality of 81 DN from female patients using X-chromosome inactivation mosaicism and polymorphism of androgen receptor (AR) gene. Then we examined these samples for chromosomal loss of heterozygosity (LOH) at 11 microsatellite polymorphism sites. The results demonstrated that GPC3 immunoreactivity was detected in 103 of 136 HCC (75.7%) and 19 of 103 DN (18.4%), and the positive ratio correlated with HBsAg positivity. Clonality assays showed that 15 GPC3-positive DN from female patients, including 12 high-grade DN (HGDN), and 28 (42.4%) of 66 GPC3-negative DN, were monoclonal. In addition, among 19 GPC3-positive DN, chromosomal LOH was found at loci D6S1008 (100%, 19/19), D8S262 (52.6%, 10/19) and D11S1301 (57.9%, 11/19). However, the LOH frequency in GPC3-negative DN was 5.95% (5/84), 23.8% (20/84), and 4.76% (4/84) in three loci, respectively. Thus, we concluded that GPC3-positive DN, especially GPC3-positive HGDN, was really a late premalignant lesion of HCC.
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Li
L
Gong
Department of Nuclear Medicine, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Long-Xiao
LX
Wei
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Pin
P
Ren
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Wen-Dong
WD
Zhang
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Xiao-Yan
XY
Liu
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Xiu-Juan
XJ
Han
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Li
L
Yao
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Shao-Jun
SJ
Zhu
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Miao
M
Lan
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China ; Department of Gynaecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Yan-Hong
YH
Li
The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P.R China.
Wei
W
Zhang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D053673:Glypicans / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009030:Mosaicism; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics; D012307:Risk Factors; D049951:X Chromosome Inactivation / Q000235:genetics
D053673:Glypicans; D011944:Receptors, Androgen