Glypican-3, GPC-3

GPC-3 is a heparin sulphate proteoglycan and an oncofetal protein. The gene encoding this protein is located at Xq26. Deletion of the gene is associated with Simpson-Golabi-Behmel syndrome, a rare X-linked overgrowth syndrome with craniofacial, skeletal, and genitourinary abnormalities.

GPC-3 may be a useful serum marker in patients with hepatocellular carcinoma or melanoma2,4.

Immunohistochemical expression

Normal tissues:

Normal tissues negative for GPC-3:

 

Neoplasms positive for GPC-3:

 

 

GPC-3

AFP

CD34

Hep Par 1

HSP70

Glutamine synthetase

 
 

Liver

Normal hepatocytes

0/92 , 0/256

0/456

negative8

45/456

 

 

 
 

Fetal liver

9/96

 

 

 

 

 

 
 

Fulminant hepatitis

0/32 , 0/96

 

 

 

 

 

 
 

Regenerative nodule in fulminant hepatitis

1/16

 

 

 

 

 

 
 

Autoimmune hepatitis

0/26

 

 

 

 

 

 
 

Primary sclerosing cholangitis

0/16

 

 

 

 

 

 
 

Chronic viral hepatitis

0/136

 

 

 

 

 

 
 

Primary biliary cirrhosis

0/26

 

 

 

 

 

 
 

Cirrhotic liver

0/222, 0/436, 4/788, 0/1510

 

negative8 

 

0/1510

 

 
 

Focal nodular hyperplasia

0/42, 1/36, 0/168 , 0/1111

 

incomplete8 

 

 

 

 
 

Hepatic adenoma

0/72, 0/76, 0/198

 

incomplete8 

 

 

 

 
 

Dysplastic nodule, low grade

0/72, 2/86 , 0/1411, 2/6512

 

 

 

0/1510

 

 
 

Dysplastic nodule, high grade

1/52, 6/86 , 2/2911, 14/2912, 2/2210

 

 

 

1/2210

9/2210

 
 

Hepatocellular carcinoma

ordinary

19/232, 14/145, 47/566, 93/1068, 46/5911, 37/4912, 39/5310

4/162, 17/456

complete8 

38/456

39/5310

37/5310

 
 

fibrolamellar

1/32, 1/512

 

 

 

 

 

 
 

sarcomatoid

0/36, 1/18

 

 

 

 

 

 
 

Mixed hepatocellular carcinoma and cholangiocarcinoma

1/32, 7/912

 

 

 

 

 

 
 

Cholangiocarcinoma

0/12, 0/166, 0/148, 1/1012

 

 

 

 

 

 
 

Hepatoblastoma

6/62

 

 

 

 

 

 
 

Carcinoid

0/16

 

 

 

 

 

 
 

Colonic carcinoma metastatic to liver

1/236

 

 

 

 

 

 
 

 

GPC-3

AFP

CK7

 
 

Yolk sac tumour (11 ovary, 6 testis, 4 mediastinum, 3 abdomen, 5 brain/pineal, 2 retroperitoneum, 1 supraclavicular, 1 uterine)

pure

15/161

16/161

1/161

 

mixed

17/171

14/171

14/171

Testis

Yolk sac tumour

25/253, 24/247

 

 

Teratoma

2/103 , 6/367

 

 

Syncytiotrophoblastic giant cell component

10/143

 

 

Choriocarcinoma

1/33 , 7/77

 

 

Intracellular germ cell neoplasia unclassified

0/333

 

 

Seminoma

0/613, 0/427

 

 

Embryonal carcinoma

0/193, 3/377

 

 

various

2/148

 

 

Ovary

clear cell carcinoma

7/421, 1/28

12/421

42/421

Endometrioid carcinoma

2/321, 1/78

 

 

Serous carcinoma

1/1571, 0/58

 

 

Serous tumor of low malignant potential

0/591

 

 

Mucinous carcinoma

0/101

 

 

Sex cord stromal tumour

0/161

 

 

Carcinosarcoma

0/41

 

 

Undifferentiated carcinoma

0/21

 

 

Peritoneum

Serous carcinoma

0/381

 

 

           

 

 

Melanocytic naevus

10/119

 

Melanoma

17/219

   

 

Other tumours are almost all negative for Glypican-3:

 

Adrenal

cortical carcinoma

0/108

 

Bladder

urothelial carcinoma

0/158

Breast

adenocarcinoma

0/58

Colon

adenocarcinoma

0/108

Gastrointestinal tract and lung

carcinoid

3/158

Kidney

renal cell carcinoma

0/108

Lung

adenocarcinoma

0/118

Pancreas

adenocarcinoma

0/138

Prostate

adenocarcinoma

0/118

Pleura/peritoneum

mesothelioma

0/78

Salivary gland

pleomorphic adenoma and Warthin tumour

0/108

Skin

basal cell carcinoma

0/108

Soft tissue

epithelioid carcinoma

0/108

Stomach

adenocarcinoma

0/88

Thyroid

various

0/288

Uterus

adenocarcinoma

0/108

     

 Diagnostic utility

References

1 Esheba Oncofetal Protein Glypican-3 Distinguishes Yolk Sac Tumor From Clear Cell Carcinoma of the Ovary. Am J Surg Pathol 2008;32:600–607

2 Capurro M, Wanless IR, Sherman M, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 2003; 125:89-97

3 Ota S, Hishinuma M, Yamauchi N, et al. Oncofetal protein glypican-3 in testicular germ-cell tumor. Virchows Arch 2006; 449:308-14

4 Nakatsura T,Nishimura Y. Usefulness of the novel oncofetal antigen glypican-3 for diagnosis of hepatocellular carcinoma and melanoma. BioDrugs 2005; 19:71-7

5 Nakatsura T, Yoshitake Y, Senju S, et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun 2003; 306:16-25

6 Yamauchi N, Watanabe A, Hishinuma M, et al. The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol 2005; 18:1591-8 FULL TEXT

7 Zynger DL, Dimov ND, Luan C, et al. Glypican 3: a novel marker in testicular germ cell tumors. Am J Surg Pathol 2006; 30:1570-5

8 Coston WM, Loera S, Lau SK, et al. Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol 2008; 32:433-44

9 Nakatsura T, Kageshita T, Ito S, et al. Identification of glypican-3 as a novel tumor marker for melanoma. Clin Cancer Res 2004; 10:6612-21 FULL TEXT

10 Di Tommaso L, Franchi G, Park YN, et al. Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology 2007; 45:725-34

11 Libbrecht L, Severi T, Cassiman D, et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol 2006; 30:1405-11

12 Wang XY, Degos F, Dubois S, et al. Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas. Hum Pathol 2006; 37:1435-41

 

This page last revised 29.4.2008.

©SMUHT/PW Bishop