Utility of Brachyury as a New-Age Marker in the Diagnosis of Chordomas
B Rekhi, K Thorat, NA Jambhekar, R Dikshit, M Agrawal, A Puri. Tata Memorial Hospital, Mumbai, Maharashtra, India
Background: Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker to substantiate a diagnosis of a chordoma.
Design: One hundred and four tumors were evaluated for immunohistochemical (IHC) expression of brachyury. These comprised 46 chordomas and 58 other tumors (26 chondroid tumors, 7 liposarcomas, 4 pleomorphic adenomas, 4 mucoepidermoid carcinomas, 4 mucinous adenocarcinomas, 6 germ cell tumors and 2 cases of renal cell carcinoma). Brachyury expression was graded as nil (0), focal nuclear (+), strong (++) and very strong (+++). Only intranuclear (++) and (+++) were regarded as positive. IHC results for CK, EMA and S100 were available in 20 of the 46 chordomas.
Results: The location of chordomas was sacrococcyx in 29 (63%) cases; base of skull in 8 (17.4%) cases and spine in 9 (19.6%) cases. The histology was classical in 33 (71.7%) cases and 11 (23.9%) cases had chondroid matrix. Remaining 1 (2.2%) case, each was labeled as a chondroid chordoma and a de-differentiated chordoma, respectively. Forty out of 46 chordomas (86.9%) displayed positive brachyury staining. While the de-differentiated area in 1 case was negative, the chondroid matrix showed positive staining. None of the 58 other tumors revealed brachyury positivity. The 6 germ cell tumors, including 4 cases of seminoma displayed focal (+) staining, while 1 case, each of embryonal carcinoma and a teratoma, respectively, showed nil staining. Specificity for Brachyury staining in chordomas vs. its differential diagnoses was 100% and sensitivity was 86.9% (CI = 73.7-95.1%). Among the conventional IHC markers, 20 of 20 chordomas (100%) showed CK positivity; 19 of 19 such cases (100%) showed EMA positivity and 16 of 18 chordomas (88.9%) displayed S100 positivity.
Conclusions: Brachyury is a single, fairly specific new-age marker to substantiate a diagnosis of a chordoma, including its variants. We observed its negativity in lesions which usually form its differential diagnoses. Only strong, intranuclear positivity should be interpreted as positive staining.
Category: Bone & Soft Tissue
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 15, Tuesday Morning