Evaluation of epithelial and keratin markers in glioblastoma multiforme: an immunohistochemical study

Abstract

Objective: Poorly differentiated metastatic carcinoma may be difficult to distinguish histologically from high-grade astrocytic malignant neoplasms, particularly on small open or stereotactic biopsy specimens. Previous authors have reported that a subset of glioblastoma multiforme (GBM) variably stains with cytokeratin immunomarkers. The authors examined a panel of epithelial and keratin antibodies by paraffin immunohistochemistry to evaluate the immunophenotype of GBM for these markers and to determine what combination of immunostains would be optimal in distinguishing GBM from metastatic carcinoma.

Methods: Twenty-three patients with GBM (age range, 19-86 years; mean, 63.4 years; 14 men and 9 women) and 22 patients with metastatic carcinoma (age range, 26-77 years; mean, 58.1 years; 7 men and 15 women) to the brain were studied with a panel of immunostains, including glial fibrillary acid protein (GFAP), Ber-EP4, antikeratin monoclonal antibodies AE1/3, and antibodies to CAM 5.2 and cytokeratins 7 (CK7) and 20 (CK20). Sites of origin for the metastatic tumors included lung (n = 11), breast (n = 5), endometrium (n = 1), prostate (n = 1), colon (n = 1), presumed kidney (n = 1), and unknown (n = 2).

Results: All GBMs stained positive for GFAP (100%), and all but 1 (95.7%) stained positive for cytokeratins AE1/3. Only rare focal immunoreactivity was observed in a single case of GBM with CAM 5.2 (4.3%), CK7 (4.3%), and CK20 (4.3%). Immunoreactivity with Ber-EP4 was not observed in any of the GBMs (0.0%). All cases of metastatic carcinoma stained positive with cytokeratins AE1/3 (100%) and CAM 5.2 (100%). Variable staining was observed in carcinomas with CK7 (17 of 22, 77.3%), Ber-EP4 (11 of 22, 50.0%), and CK20 (9 of 22, 40.9%). Three metastatic carcinomas showed rare GFAP-positive staining cells (13.6%).

Conclusions: Based on the aforementioned results, a combination of immunostains, including GFAP and cytokeratin CAM5.2, may be the most useful in differentiating poorly differentiated metastatic carcinoma from GBM. A significant number of GBMs stain with some cytokeratin markers, in particular cytokeratins AE1/3. Because of the poor specificity of cytokeratins AE1/3 in distinguishing metastatic carcinoma from GBM, it should not be used to differentiate the 2 entities.