Expression of glypican-3 in undifferentiated embryonal sarcoma and mesenchymal hamartoma of the liver

Abstract

Summary Glypican-3 (GPC3) is an oncofetal protein that has been demonstrated to be a useful diagnostic immunomarker for hepatocellular carcinoma and hepatoblastoma. Its expression in mesenchymal tumors of the liver, particularly undifferentiated embryonal sarcoma (UES) and mesenchymal hamartoma (MH), has not been investigated. In this study, a total of 24 UESs and 18 MHs were immunohistochemically stained for GPC3 expression. The results showed cytoplasmic staining for GPC3 in 14 (58%) UESs, of which 6 exhibited diffuse immunoreactivity and the remaining 8 showed focal positivity. The patients with GPC3-positive UES tended to be younger (mean 18 years; median 11 years) than those with GPC3-negative tumors (mean 39.4 years; median 27 years), although the difference did not reach statistical significance (P = .06). Eight MHs also exhibited GPC3 immunoreactivity (44%; 4 diffuse and 4 focal). Positive staining in all 8 cases was primarily seen in entrapped nonlesional hepatocytes with a canalicular and cytoplasmic staining pattern. In only 4 cases (22%) was GPC3 immunoreactivity also observed in the mesenchymal component. The patients with positive staining also tended to be younger (mean 2.6 years; median 1.1 years) compared with those with negative staining (mean 16.3 years; median 4.5 years), but the difference was not statistically significant (P = .15). Our data demonstrate that GPC3 is expressed in a subset of UES and MH of the liver. Caution should thus be exercised when evaluating a GPC3-expressing hepatic neoplasm, particularly on a needle biopsy when the differential diagnosis includes poorly differentiated hepatocellular carcinoma or hepatoblastoma.

Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium

“…Hepatobiliary rhabdomyosarcoma also occurs in children under 5 years of age and may demonstrate glypican 3 positivity. 55 Some embryonal sarcomas share a 19q13.4 chromosomal rearrangement and the translocation t(11;19) with mesenchymal hamartoma (Table 4) 56 that usually affect infants and children in the first 2 years of life and in the past was considered a developmental disorder. However, the identification of the same translocation t(11;19)(q13;q13.4) in some cases has demonstrated its neoplastic nature.…”

Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity

“…Glypican-3 (GPC3), a membrane-bound proteoglycan, is expressed in several solid tumors including hepatocellular carcinoma (HCC), hepatoblastoma, embryonal sarcoma, malignant rhabdoid tumor (MRT), yolk sac tumor, Wilm's tumor, squamous cell carcinoma of the lung, and liposarcoma. [19][20][21][22][23][24][25][26][27][28][29] GPC3 is an attractive target for immunotherapy since it is not expressed at detectable levels in nonmalignant tissues including normal or cirrhotic liver. [19][20][21][22] In addition, GPC3 expression in HCC is associated with significantly worse prognosis even after complete tumor removal, likely due to GPC3's ability to enhance wnt signaling and stimulate tumor growth.…”

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

“…Finally, GPC3 expression is not HCC specific. Frequent expression has been documented in a number of neoplasms, such as hepatoblastoma, 117 undifferentiated embryonal sarcoma of the liver, 118 yolk sac tumor, 119,120 choriocarcinoma, 121 pancreatic acinar cell carcinoma, 110,121 Merkel cell carcinoma, 122 and lung squamous cell carcinoma. 123 Positive staining has also been reported in a small fraction of adenocarcinomas of the esophagus, stomach, small bowel, and colon.…”