Oh D, Prayson R A
Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Arch Pathol Lab Med. 1999 Oct;123(10):917-20. doi: 10.5858/1999-123-0917-EOEAKM.
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.
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).
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%).
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.
低分化转移性癌在组织学上可能难以与高级别星形细胞恶性肿瘤区分，尤其是在小的开放活检或立体定向活检标本上。既往有作者报道多形性胶质母细胞瘤（GBM）的一个亚群对细胞角蛋白免疫标志物呈可变染色。作者通过石蜡免疫组织化学检测了一组上皮和角蛋白抗体，以评估GBM对这些标志物的免疫表型，并确定哪种免疫染色组合在区分GBM与转移性癌方面最为理想。
对23例GBM患者（年龄范围19 - 86岁；平均63.4岁；14例男性和9例女性）和22例脑转移癌患者（年龄范围26 - 77岁；平均58.1岁；7例男性和15例女性）进行了一组免疫染色研究，包括胶质纤维酸性蛋白（GFAP）、Ber-EP4、抗角蛋白单克隆抗体AE1/3以及针对CAM 5.2和细胞角蛋白7（CK7）及20（CK20）的抗体。转移性肿瘤的原发部位包括肺（n = 11）、乳腺（n = 5）、子宫内膜（n = 1）、前列腺（n = 1）、结肠（n = 1）、推测为肾（n = 1）和不明（n = 2）。
所有GBM对GFAP染色均呈阳性（100%），除1例（95.7%）外，所有GBM对细胞角蛋白AE1/3染色均呈阳性。在1例GBM中仅观察到罕见的局灶性CAM 5.2（4.3%）、CK7（4.3%）和CK20（4.3%）免疫反应性。所有GBM均未观察到与Ber-EP4的免疫反应性（0.0%）。所有转移性癌病例对细胞角蛋白AE1/3（100%）和CAM 5.2（1...显示全部内容
所有GBM对GFAP染色均呈阳性（100%），除1例（95.7%）外，所有GBM对细胞角蛋白AE1/3染色均呈阳性。在1例GBM中仅观察到罕见的局灶性CAM 5.2（4.3%）、CK7（4.3%）和CK20（4.3%）免疫反应性。所有GBM均未观察到与Ber-EP4的免疫反应性（0.0%）。所有转移性癌病例对细胞角蛋白AE1/3（100%）和CAM 5.2（100%）染色均呈阳性。在CK7（22例中的17例，77.3%）、Ber-EP4（22例中的11例，50.0%）和CK20（22例中的9例，40.9%）染色中，癌组织呈现可变染色。3例转移性癌显示罕见的GFAP阳性染色细胞（13.6%）。
基于上述结果，包括GFAP和细胞角蛋白CAM5.2在内的免疫染色组合可能在区分低分化转移性癌与GBM方面最有用。相当数量的GBM对某些细胞角蛋白标志物染色，尤其是细胞角蛋白AE1/3。由于细胞角蛋白AE1/3在区分转移性癌与GBM方面特异性较差，不应将其用于区分这两种实体。
