General

• COX2 was detected by immunohistochemical analysis in 19 (90%) of 21 chordomas. [1]
• The cartilage-typical large aggregating proteoglycan aggrecan was present throughout all chordomas and, thus, a very characteristic gene product and marker of these neoplasms. [2]
• HMW-MAA was detected in 13 of 21 chordomas (62%). [3]
• Telomerase activity was observed in 1 of 2 chordoma tumors, but only at 1% of the activity of HeLa cells. [4]
• Intraosseous benign notochordal cell tumors (BNCT) were found in 7.3% (6/82) sacrectomy/coccygectomy surgical specimens. In 4 cases the BNCT was immediately adjacent to the chordoma, whereas in 2 cases it was in a bone uninvolved by the chordoma. keratin performed on 2 of the BNCTs showed that both lesions were diffusely and strongly positive for keratin. [5]
• The chondroid areas of 7 chondroid chordomas expressed aggrecan and glycosaminoglycans. In situ hybridization showed high mRNA expression levels for aggrecan in neoplastic cells of classic and chondroid chordoma; thus, this aggrecan-rich matrix was is not produced by surrounding nonneoplastic stromal cells. [6]
• The mean MIB-1 labeling index in 22 chordomas was 0.5 (range, 0 to 3.8). [7]
• Mean cyclin D1 LI in 22 chordomas was 35.6 (range, 0 to 82.4). [7]
• A fate-mapping experiment found that the majority of mouse notochord cells ended up within the nucleus pulposus, however a small number of cells were found to reside, and persist throughout life, in the vertebral column, primarily in the middle of each vertebrae along the ventral surface. These notochordal remnants were found along the entire length of the vertebral column in all twelve animals examined. [8]
• 6 of 6 chordomas showed moderate to strong staining for galectin-3. Subcellularly, galectin-3 was localized mostly in the cytoplasm, while a subset of tumor cells also showed nuclear distribution. Differences in staining patterns of chordoma cells could not be correlated to any histological features of these tumors. [9]
• The MIB-1 proliferative index was significantly higher in grade 2 or 3 lesions than in grade 1 lesions (P = .014), and the MIB-1 index tended to be higher in solid type than in trabecular type tumors (P = .088). [10]
• Higher nuclear atypia (grade 2 or 3) occurred in 5 of 9 solid type chordoma specimens and 0 of 8 trabecular type specimens. [10]
• Alterations in cyclin D1 and pRb were seen more often in recurrent SBCs than in primary SBCs. [11]
• Compared with primary lesions, MIB-1 LI was significantly increased in recurrent SBCs (mean, 7.2), but not in recurrent NSBCs, leading to differences in MIB-1 LI between recurrent SBCs and NSBCs (P = 0.006). [12]
• The mean proliferation potential index of chordoma cells was significantly higher than in notochordal cells (P=0.01). [13]
• In NSBCs, intralesional fibrous septum and lobular growth patterns were associated with nuclear pleomorphism, mitosis, and the MIB-1 labeling index. [14]
• SOX-9 is common to both notochordal and cartilaginous differentiation, and is not useful in the chordoma-chondrosarcoma differential diagnosis. [15]
• Chordomas were not found to express high levels of the hypertrophic gene collagen X, platelet-derived growth factor alpha, or reticulocalbin 3. [16]
• Immunohistochemical staining with HMW-MAA-specific mAb resulted in the staining of 62% of 21 chordomas tested. [3]
• 13 of 13 chordomas expressed GLUT-1. 3 of 13 showed expression in 25-50% of cells and 10 of 13 showed expression in more than 50% of cells. [17]
• The mean percentage of p75 expression was very similar in chordoma and notochordal cells (97.3% ± 1.6% vs. 96.3% ± 2.0%, P = 0.394). [13]
• 2-DE found 14 proteins as being up-regulated and 5 proteins as being down-regulated through comparing tumor and normal tissue taken from 6 patients with cervical or sacral spine chordomas. [18]
• Proteins identified via MALDI-TOF MS as up-regulated from 6 chordoma samples (cervical or sacral spine tumors) were ENO1 (counted twice), creatine kinase (muscle), keratin-10, smooth muscle and non-muscle myosin alkali light chain 6B, PKM2, keratin-10 (type I; cytoskeletal), chain A human muscle L-lactate dehydrogenase M chain ternary complex with Nadh and oxamate, M2-type pyruvate kinase, cytosolic thyroid hormone-binding protein, heat shock protein gp96 precursor, chain B crystal structure of fibrinogen fragment D, and enolase 1. Results for ENO1, PKM2, and gp96 were confirmed by Western blot. [18]
• Proteins identified via MALDI-TOF as down-regulated from 6 chordoma samples (cervical or sacral spine tumors) were transferrin, myosin:SUBUNIT = light chain:ISOTYPE = V/sB (counted twice), type II keratin subunit protein, hypothetical protein. [18]
• ENO1, PKM2, and gp96, proteins known to be up-regulated in various human cancers, displayed higher expression in recurring than primary tumors among 30 chordoma samples from patients with cervical or sacral spine tumors, as shown by immunohistochemistry. [18]
• 8/25 primary clival chordoma specimens demonstrated nuclear Ki-67 proliferation index of 5% or greater. These patients had a 56% reduction in mean survival time compared to those with tumors demonstrating Ki-67 PI of less than 5%. [19]
• 23/35 chordomas were negative for RPS6. [20]
• Western blot analysis using a Ser240-244 phospho-antibody on tumor samples from 22 patients with classic, sporadic chordoma found low expression of activated S6 in 11 of 22 (50%) samples, no expression of S6 in 8 of 22 (36%) samples, and expression of unphosphorylated S6 in 3 of 22 (14%) samples. This trend of low level activation was confirmed on 13 samples using a Ser235-235 phospho-antibody. [21]
• Immunohistochemistry on 11 primary tumor samples from patients with skull base chordoma detected 5.6 ± 4.6% of cells as being Ki-67 positive. [22]
• Immunohistochemistry on 8 recurrent tumor samples from patients with skull base chordoma detected 10.2 ± 7.4% of cells as being Ki-67 positive. This was not a statistically significant increase over the percent of cells that were Ki-67 positive in primary tumor samples. [22]
• Among 4 poorly differentiated chordoma samples from pediatric patients (age range: 22 months to 11 years), 3 samples demonstrated focal nuclear and cytoplasmic S-100 staining. [23]
• Immunohistochemistry revealed lack of SMARCB1/INI1 expression in all samples from 4 pediatric patients (age range: 22 months to 11 years) with poorly differentiated chordoma and 8 patients with atypical teratoid/rhabdoid tumors. In contrast, SMARCB1/INI1 staining was positive in 10 samples from patients with typical chordoma (age range: 11 to 77 years). [23]
• Immunohistochemistry revealed expression of S100 in 18 of 22 (81.8%) samples of chordoma, 18 of 20 (90%) samples of chondrosarcoma, 12 of 12 (100%) samples of enchondroma, and 0 of 2 (0%) samples of chordoid meningioma. [24]
• Immunohistochemistry revealed expression of M2A antigen (antibody: D2-40) in 0 of 22 (0%) samples of chordoma, 17 of 20 (85%) samples of chondrosarcoma, 12 of 12 (100%) samples of enchondroma, and 2 of 2 (100%) samples of chordoid meningioma. [24]
• Immunohistochemistry revealed expression of alpha-catenin in 7 of 15 (46.7%) chordoma samples, compared with expression in 1 of 8 (12.5%) chondrosarcoma samples. 3 of the 7 (42.9%) chordoma samples demonstrated immunoreactivity in more than 50% of the investigated cells. [25]
• Immunohistochemistry revealed expression of beta-catenin in 13 of 15 (86.7%) chordoma samples, compared with expression in 1 of 8 (12.5%) chondrosarcoma samples. 4 of the 13 (30.8%) chordoma samples demonstrated immunoreactivity in more than 50% of the investigated cells. [25]
• Immunohistochemistry revealed expression of gamma-catenin in 10 of 15 (66.7%) chordoma samples, compared with expression in 0 of 8 (0%) chondrosarcoma samples. 2 of the 10 (20.0%) chordoma samples demonstrated immunoreactivity in more than 50% of the investigated cells. [25]
• Immunohistochemistry on 17 intracranial chordoma samples from 10 patients found a statistically significant difference between the Ki-67 staining index (SI) of non-recurrent (n = 7; SI = 2.8%) and recurrent (n = 10; SI = 10.2%) tumors. [26]
• Immunohistochemistry on 17 intracranial chordoma samples from 10 patients found cyclin D1 immunoreactivity in 2 of 7 (28.6%) non-recurrent tumors and in 6 of 10 (60%) recurrent tumors. The Ki-67 SI was 4.5% among cyclin D1 immuno-negative samples and 10.3% among cyclin D1 immuno-positive samples. [26]
• Immunohistochemistry on 35 chordoma samples from 28 patients revealed cytoplasmic reactivity for HBME in 35 of 35 (100.0%) samples. [27]
• Immunohistochemistry revealed predominantly focal staining for S100 in 31 of 33 (93.9%) chordoma samples. [27]
• Immunohistochemistry revealed cytoplasmic reactivity for neuron-specific enolase (NSE) in 33 of 33 (100%) chordoma samples. [27]
• Immunohistochemistry revealed predominantly focal staining for synaptophysin (Syp) in 3 of 33 (9.1%) chordoma samples. [27]
• Immunohistochemistry revealed positive staining for chromogranin (Chr) in 0 of 26 (0%) chordoma samples. [27]
• Immunohistochemistry revealed positive staining for S100 in 7 of 16 (43.8%) classical chordoma samples and in 21 of 25 (84%) chondroid chordoma samples. [28]
• Immunohistochemistry revealed positive staining for S-100 in 4 of 6 (66.7%) mediastinal chordoma samples. [29]
• Immunohistochemistry on 50 primary chordoma samples found positive cytoplasmic staining for MDR1 in 5 (10%) cases, for MRP1 in 37 (74%) cases, and for HIF-1α in 40 (80%) cases. There was a statistically significant positive correlation between expression of MRP1 and HIF-1α. [30]

Nuclear Receptors

• Androgen (AR) was detected in 19 of 21 chordomas, with the number of AR+ nuclei varying widely from case to case (mean ± SD, 72% ± 36% of nuclei; range, 5%-100 %). [1]
• No specific nuclear staining was observed for ER-α or PR among 21 chordomas. [1]
• ER-β was detected in 21 of 21 chordomas (mean ± SD, 72% ± 25% of nuclei; range, 20%-100%). [1]
• All studied chordomas expressed both PR and ER - alpha. [31]

Brachyury (T)

• Out of 35 skull-base chordomas, all were positive for brachyury expression [32]
• Brachyury protein was detected in the fetal notochord and in 53 of 53 chordomas but was not detected in the nucleus pulposus or over 300 neoplasms, including 163 chondroid tumours. [16]
• Brachyury protein was detected by IHC in 51 of 57 (89%) chordomas. [15]
• Positivity for cytokeratin and Brachyury had a sensitivity of 98% and specificity of 100% for detecting chordoma. [15]
• Immunohistochemistry on 51 human axial chordoma samples from the sacrococcyx, spine, and skull base showed 46 of 51 (90.2%) samples as positive for brachyury, while 58 of 58 (100%) non-chordomatous tumor samples were negative for brachyury. [33]
• Immunohistochemistry on 51 human axial chordoma samples from the sacrococcyx, spine, and skull base showed diffuse staining for brachyury in 30 of 34 (88.2%) classical chordoma samples, 12 of 13 (92.3%) chordoma samples with a dominant chondroid matrix, and 2 of 2 (100%) chondroid chordoma samples. In 2 of 2 (100%) de-differentiated chordoma samples, positive brachyury staining was found in the differentiated region and negative staining was found in the de-differentiated region. [33]
• Immunohistochemistry revealed positive brachyury staining in all samples from 4 pediatric patients (age range: 22 months to 11 years) with poorly differentiated chordoma and 10 patients (age range: 11 to 77 years) with typical chordoma. In contrast, brachyury staining was negative in 8 samples from patients with atypical teratoid/rhabdoid tumors. [23]

p53

• No p53 immunostaining was observed in 15 of 22 tumors, 1+ staining in 2 of 22 tumors, 2+ staining in 3 of 22 tumors, and 3+ staining in 2 of 22 tumors. [7]
• No bcl-2 immunostaining was observed in 19 of 22 tumors, 1+ staining was noted in 2 of 22 tumors, and 3+ staining was noted in 1 of 22 tumors. [7]
• p53 overexpression was detected in two specimens of solid type, and the MIB-1 LI in these two specimens was significantly higher (P = .037) than that in the specimens without p53 overexpression. [10]
• Immunohistochemical analysis of chordoma tumors revealed p53 overexpression in 30.4% of SBCs and 20.8% of NSBCs; MDM2 overexpression in 8.7% of SBCs and in 16.7% NSBCs; and cyclin D1 overexpression in 26.1% of SBCs and in 50.0% of NSBCs. Possible pRb overexpression was detected in 37% of SBCs and in 62.5% of NSBCs. Few chordomas expressed p27Kip1 or p16INK4a. [11]
• A mdm2 amplification was detected in 8 of 52 samples(15.4%) tumors. MDM2 overexpression was not associated with mdm2 amplification. [11]
• Alterations of p53, MDM2, cyclin D1, and pRb proteins were found to have cooperative effects on both higher proliferative ability (MIB-1 labeling index) and increased nuclear pleomorphism, a previously described prognostic indicator for patients with chordoma. In recurrent lesions, only p53 overexpression and MDM2 overexpression were associated with higher MIB-1 LI. No correlation was detected between cell cycle althigher MIB-1 LI. No correlation was detected between cell cycle alterations and nuclear pleomorphism in patients with recurrent lesions. [11]
• p53 overexpression was correlated significantly with the overexpression of MDM2 and cyclin D1. [11]
• For forty patients who had primary lesions, the 5-year survival rate was 38.9% for patients with p53 overexpression and 79.4% for patients without p53 overexpression. [11]
• The mean apoptosis index of chordoma cells was significantly lower compared with that of notochordal cells (P=0.03). [13]
• CDKN2A was detected by IHC in only 5 of 48 chordomas. [34]
• 11/25 primary clival chordoma specimens demonstrated p53 accumulation. There was, however, no correlation between p53 level and survival in these patients. [19]
• Immunohistochemistry on 11 primary tumor samples from patients with skull base chordoma detected 9.0 ± 9.4% of cells as being p53 positive. [22]
• Immunohistochemistry on 8 recurrent tumor samples from patients with skull base chordoma detected 16.5 ± 12.0% of cells as being p53 positive. This was not a statistically significant increase over the percent of cells that were p53 positive in primary tumor samples. [22]
• Immunohistochemistry on 11 primary tumor samples from patients with skull base chordoma followed by statistical analysis found a highly significant correlation between Ki-67 and p53 expression. [22]
• Immunohistochemistry on 8 recurrent tumor samples from patients with skull base chordoma followed by statistical analysis found a highly significant correlation between Ki-67 and p53 expression in primary and recurrent tumor samples. [22]
• p53 protein mutation co-occurred with hTERT mRNA expression in 27 of 29 (93.1%) classic, skull base chordoma samples. [35]
• Immunohistochemistry on 17 intracranial chordoma samples from 10 patients found p53 immunoreactivity in 0 of 7 (0%) non-recurrent tumors and in 9 of 10 (90%) recurrent tumors. The Ki-67 SI was 3.3% among p53 immuno-negative samples and 10.7% among immuno-positive samples. [26]

Cytoskeletal Markers

• All chordomas were positive for keratin but negative for GFAP. [36]
• Cytokeratins and an epithelial membrane-specific oligosaccharide sequence are found in chordomas but not in chondrosarcomas or normal cartilage [37].
• CK18 was detected in 34 of 34 benign notochordal cell tumors and 3 of 3 chordomas but 0 of 27 notochordal vestiges. [38]
• Immunodetection of S-100 protein and vimentin showed strong staining in neoplastic cells throughout 22 of 22 chordomas. [6]
• Cytokeratin 19 and EMA were positive in 15 of 15 classic chordomas. Cytokeratin 19 and EMA were positive in chordoid areas and in part of the chondrocyte-like cells in 7 of 7 chondroid chordomas. The chondrocyte-like cells in the centers of the chondroid areas were negative for these epithelial cell markers. [6]
• Cytokeratin and S-100 were expressed in five conventional chordomas and among a few cells with physaliphorous appearance in two chondroid chordoma cases. [39]
• Most of 34 notochordal lesions found in autopsy cases and 3 classic chordomas demonstrated positive immunostaining for vimentin, S-100 protein, epithelial membrane antigen, CAM 5.2, AE1/AE3, and CK18. 27 notochordal vestiges in the fetal intervertebral discs failed to demonstrate any positive reaction for CK18, although the other antigens were positive. [38]
• 26 of 26 lesions demonstrated positive immunostaining with vimentin, S100 protein, EMA, AE1⁄AE3 and CAM5.2. [40]
• No significant correlations were seen between the expression of proteinases and age, sex, nuclear pleomorphism, apoptosis, or necrosis in the four groups: primary lesions with and without tumor infiltration, and recurrent lesions with and without tumor infiltration. No significant correlations were seen between the expression of proteinases and pancytokeratin or vimentin in each group. [41]
• Immunohistochemistry on human axial chordoma samples from the sacrococcyx, spine, and skull base showed 23 of 23 (100%) samples as positive for CK, 22 of 22 (100%) samples as positive for EMA, 18 of 21 (85.7%) samples as positive for S100, and 10 of 10 (100%) samples as positive for vimentin. [33]
• Immunohistochemistry revealed expression of cytokeratin (antibody: PANCK) in 22 of 22 (100%) samples of chordoma, 1 of 20 (0.5%) samples of chondrosarcoma, 0 of 12 (0%) samples of enchondroma, and 0 of 2 (0%) samples of chordoid meningioma. [24]
• 15 of 15 (100%) tumor samples from 15 patients with chordoma demonstrated immunoreactivity for S-100, vimentin, cytokeratin 8, and cytokeratin 19. [25]
• Immunohistochemistry on 35 chordoma samples from 28 patients revealed positive staining for keratins K8 and K19 in 35 of 35 (100%) samples. [27]
• Immunohistochemistry revealed positive staining for keratin K5 in 22 of 26 (84.6%) chordoma samples. [27]
• Immunohistochemistry on 35 chordoma samples from 28 patients revealed predominantly focal staining for keratin K7 in 9 of 35 (25.7%) samples. [27]
• Immunohistochemistry on 35 chordoma samples from 28 patients revealed predominantly focal staining for keratin K20 in 7 of 35 (20.0%) samples. [27]
• Immunohistochemistry revealed positive staining for keratins K16 and K17 in 0 of 26 (0%) chordoma samples. [27]
• Immunohistochemistry revealed positive staining for EMA and S100 in 28 of 28 (100%) skull base chordoma samples. Similarly, positive staining for cytokeratin was seen in 27 of 28 (96.4%) samples. [42]
• Immunohistochemistry revealed positive staining for keratins (AE1 – AE3 cocktail) in 16 of 16 (100%) classical chordoma samples and in 8 of 25 (32%) chondroid chordoma samples. [28]
• Immunohistochemistry revealed positive staining for vimentin in 15 of 16 (93.8%) classical chordoma samples and in 22 of 25 (88%) chondroid chordoma samples. [28]
• Immunohistochemistry revealed positive staining for keratins, EMA, and vimentin in 6 of 6 (100%) mediastinal chordoma samples. [29]
• Immunohistochemistry on 3 recurrent samples of classic chordoma found positive staining for cytokeratin 4, cytokeratin 8, cytokeratin 18, and cytokeratin 19 in all 3 (100%) cases. In addition, vimentin stained positive in 3 (100%) of the cases, while desmin stained positive in 0 (0%) of the cases. [43]
• Immunohistochemistry on 14 chordoma samples found positive staining for cytokeratins in 13 (92.9%) cases, for EMA in 14 (100%) cases, for CEA in 3 (21.4%) cases, for S-100 in 9 (64.3%) cases, and for vimentin in 13 (92.9%) cases. In contrast, immunoreactivity for cytokeratins, EMA, and CEA was absent in 20 of 20 (100%) chondrosarcoma samples. [44]
• Immunocytology on 4 chordoma samples found positive staining for keratins, NSE, S-100, and EMA in all 4 (100%) cases. Immunoreactivity for CEA was detected in 0 (0%) of the cases. [45]
• Immunohistochemistry on 15 chordoma samples found positive staining for cytokeratins, EMA, S-100, and vimentin in all 15 (100%) cases. Immunoreactivity for neurofilaments was detected in 0 (0%) of the cases. In contrast, 6 of 6 (100%) chondrosarcomas demonstrated immunoreactivity only for S-100 and vimentin, but not for EMA, cytokeratins, or neurofilaments. Similarly, 7 of 7 (100%) carcinomas stained positive for cytokeratins and EMA, but not for S-100, vimentin, or neurofilaments. [46]
• Immunohistochemistry on 6 chordoma samples found positive cytoplasmic staining for keratin in all 6 cases (100%), whereas GFAP was negative in all cases. Some tumor cells were positive for vimentin. [36]
• Immunohistochemistry on 9 chondrosarcoma samples found positive cytoplasmic staining for vimentin in all 9 cases (100%), whereas GFAP and keratin were negative in all cases. [36]
• Immunohistochemistry on 3 myxopapillary ependymomas found positive cytoplasmic staining for GFAP in all 3 cases (100%), whereas keratin was negative in all cases. Many tumor cells were also positive for vimentin. [36]

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References