Immunohistochemical Expression of Glypican-3 in Pediatric Tumors: An Analysis of 414 Cases

Abstract

Glypican-3 (GPC3) is a proteoglycan thought to play an important role during development. Germline GPC3 mutations are seen in the rare Simpson-Golabi-Behmel syndrome (SGBS), which predisposes patients to Wilms tumor, hepatoblastoma, and neuroblastoma. While numerous adult tumors have been evaluated by immunohistochemistry for GPC3, no comprehensive assessment has been done in pediatric tumors. We therefore investigated GPC3 expression in 143 pediatric central nervous system (CNS) tumors and 271 non-CNS tumors. Among non-CNS tumors, GPC3 expression was seen in 9/9 (100%) hepatoblastomas, 4/6 (67%) malignant rhabdoid tumors, 5/13 (38%) Wilms tumors, 11/37 (30%) alveolar rhabdomyosarcomas, and 8/45 (18%) embryonal rhabdomyosarcomas. All 136 neuroblastomas, 14 Ewing sarcoma/primitive neuroectodermal tumors, and 11 synovial sarcomas were immunonegative for GPC3. Among CNS tumors, GPC3 had restricted expression, with positivity in 6/6 (100%) atypical teratoid rhabdoid tumors and 1/4 (25%) craniopharyngiomas. The remaining 136 CNS tumors-23 medulloblastomas, 21 pilocytic astrocytomas, 13 gangliogliomas, 12 ependymomas, 12 glioblastomas, 11 choroid plexus neoplasms, 10 diffuse astrocytomas (grade II/III), 10 meningiomas, 8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 3 craniopharyngiomas, 3 germinomas, and 2 neurocytomas-were entirely negative for GPC3. These results showed GPC3 positivity in a number of non-CNS tumors, with no consistent discrimination between tumors that were or were not associated with SGBS. Within the CNS, GPC3 positivity was limited to a small subset of CNS neoplasms and may thus serve as a useful positive diagnostic biomarker (P < 0.0001) in addition to negative INI1/BAF47/SMARCB1 staining to differentiate atypical teratoid rhabdoid tumors from other high-grade pediatric brain tumors.

Differential SALL4 immunoexpression in malignant rhabdoid tumours and epithelioid sarcomas

“…reported that six (43%) of 14 MRTs showed a significant extent of glypican 3 expression, whereas it was observed in only one (2%) of 48 ESs. A high prevalence of glypican 3 immunoexpression in MRTs has also been reported by other groups . Glypican 3 and SALL4 are sometimes coexpressed in tumour tissues.…”

“…A high prevalence of glypican 3 immunoexpression in MRTs has also been reported by other groups. 18,34 Glypican 3 and SALL4 are sometimes coexpressed in tumour tissues. For example, both are known to be sensitive markers for yolk sac tumour, 20,22 and the expression of glypican 3 and that of SALL4 are significantly interrelated in gastric adenocarcinomas.…”

Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma

“…Expression of GPC-3 was found in the following cancers: liver, gastric carcinoma, melanoma, highgrade urothelial carcinoma, testicular, and some uterine and vaginal cancers (1,3-6,23,28,33-35). GPC-3 expression was also reported in some non-CNS tumors of the brain (36). In various other tissue types such as colon, lung, anal, esophageal, mouth mucosa, pancreas, skin, thyroid, bladder, uterus, and vulvar tissue GPC-3 expression varied based on the type, and origin, and grade of cancer [i.e.…”

Glypican‑3 expression in malignant small round cell tumors

“…It was a predictable result that most of our NB cases (n=35) showed no GPC3 immunoreactivity, and also showed low GPC3 mRNA expression levels. Chan et al reported that the immunohistochemical GPC3 expression was entirely negative in clinical samples of NB (21), whereas Saikali and Sinnett reported increased GPC3 mRNA expression levels in most of the 10 NB cell lines they examined (11). Further studies using a larger number of NB cases are required to confirm the correlation between GPC3 immunoreactivity and the mRNA expression level.…”