No abstract

Chordoma originates from embryonic notochordal remnants in the midline along the spinal axis and is characterized by cords and lobules of neoplastic cells arranged within myxoid matrix. Because of histologic similarities with myxoid matrix and overlapping immunohistochemical profile, chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma enter in the histologic differential diagnosis at this site. Therefore, the judicious use of a panel of selected immunostains is unquestionably helpful in diagnostically challenging cases. To find useful immunohistochemical markers for assisting in differential diagnosis between chordoma and other tumors with chordoid morphology, an immunohistochemical study using D2-40, epithelial membrane antigen (EMA), pan-cytokeratin (panCK), glial fibrillary acidic protein (GFAP), S-100 protein, galectin-3, neural cell adhesion molecule (NCAM), beta-catenin, E-cadherin, and carcinoembryonic antigen was performed on 14 chordomas, 7 chondrosarcomas, 9 myxopapillary ependymomas, and 4 chordoid meningiomas. Chordoma typically showed positive for EMA and panCK and negative for D2-40 and GFAP; whereas chondrosarcoma revealed positive for D2-40, and negative for EMA, panCK, and GFAP; myxopapillary ependymoma positive for GFAP and negative for EMA; and chordoid meningioma positive for EMA, and negative for panCK and GFAP. On the basis of our immunohistochemical study, a panel of D2-40, EMA, panCK, and GFAP allowed the correct recognition of all tumors examined. Other immunohistochemical markers including S-100 protein, galectin-3, NCAM, beta-catenin, E-cadherin, and carcinoembryonic antigen were of little value in differential diagnosis. In summary, the best immunohistochemical markers useful for the evaluation of tumors with chordoid morphology were D2-40, EMA, cytokeratin, and GFAP. D2-40 was a true chondroid marker to be useful for the differential diagnosis with chordoma.

Recent studies have shown that most prostate cancers carry the TMPRSS2-ERG gene fusion. Here we evaluated the TMPRSS2-ERG gene fusion in small cell carcinoma (SCC) of the prostate (n=12) in comparison with SCC of the urinary bladder (n=12) and lung (n=11). Florescence in situ hybridization demonstrated rearrangement of the ERG gene in 8 cases of prostatic SCC (67%), and the rearrangement was associated with deletion of the 5' ERG gene in 7 cases. But rearrangement of the ERG gene was not present in any SCC of the urinary blader or lung. Next we evaluated the TMPRSS2-ERG gene fusion in nude mouse xenografts that were derived from two prostatic SCCs carrying the TMPRSS2-ERG gene fusion. Two transcripts encoded by the TMPRSS2-ERG gene fusion were detected by RT-PCR, and DNA sequencing demonstrated that the two transcripts were composed of fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene. Our study demonstrates the specific presence of TMPRSS2-ERG gene fusion in prostatic SCC, which may be helpful in distinguishing SCC of prostatic origin from non-prostatic origins. The high prevalence of the TMPRSS2-ERG gene fusion in prostatic SCC as well as adenocarcinoma implies that SCC may share a common pathogenic pathway with adenocarcinoma in the prostate.

Abstract. Pancreatic ductal adenocarcinoma (PDAC) is the major pancreatic tumor and carries an extremely poor prognosis. Coexpression of epidermal growth factor receptor (EGFR) and the HER-2 oncoprotein has been reported to be related to the invasion and an adverse clinical outcome of human pancreatic ductal adenocarcinomas. HER-2 amplification, as determined by fluorescent in situ hybridization (FISH) analysis, has been identified as a positive predictor of response to EGFR tyrosine kinase inhibitor treatment in some other cancers. The aim of this study was to investigate the coexpression rate and amplification status of HER-2 oncogene in EGFR positive pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and FISH.