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Background Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification. Methods We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases. Results According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs. Conclusions We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

Lynch syndrome (formerly called hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder caused by a germline defect in the DNA mismatch repair (MMR) system. It is characterized by early development of malignancies, particularly colorectal carcinoma (CRC) and endometrial carcinoma.1 Defective MMR systems typically induce microsatellite instability (MSI), which results in frequent mutations in cancer-related genes, ultimately contributing to carcinogenesis.2 MSI is defined as an alteration in the length of DNA microsatellite repeat sequences and is accepted as one of the major molecular phenotypes in CRCs, including sporadic tumors as well as Lynch syndrome tumors. Sporadic CRCs that are microsatellite instability-high (MSI-H) account for approximately 10% to 15% of CRCs, and hereditary MSI-H CRCs (Lynch syndrome-associated CRCs) account for approximately 3% to 5% of CRCs in Western countries.3,4 It is well known that the major cause of a defective MMR system in Lynch syndrome is a germline mutation in one of the MMR genes, including MLH1, MSH2, PMS2, or MSH6, whereas nearly all sporadic MSI-H CRCs are thought to be caused by CpG island hypermethylation in the promoter region of MLH1.2,4 Although most Lynch syndrome-associated tumors have a molecular basis of an MMR deficiency caused by germline mutations in MMR genes, Ligtenberg et al.5 recently identified another mechanism of defective MMR in a small subset of Lynch syndrome families, characterized by MSH2 promoter methylation due to germline deletions in the 3' exons of the epithelial cell adhesion molecule (EPCAM; also known as TACSTD1) gene. This molecular alteration is also referred to as MSH2 "epimutation" on the basis of its unique heritable feature of epigenetic silencing.6 Various deletions in the 3' end of the EPCAM gene have been identified in Lynch syndrome tumors, and the molecular mechanism of the MSH2 epimutation has been successfully elucidated.7,8 Interestingly, recent investigations have suggested that the loss of EPCAM protein expression could be a supportive diagnostic marker in cases of Lynch syndrome because EPCAM loss is specifically found in Lynch syndrome patients carrying EPCAM germline deletions.9,10,11 Although these findings indicate that immunohistochemistry (IHC) for EPCAM could be a simple and useful method for the screening of germline EPCAM deletion-associated Lynch syndrome patients, the studies have some limitations in that only small sample sizes originating from a few Western races (Germans and Spaniards) were investigated by only two research groups. Additional studies using larger samples from diverse ethnic groups are necessary for the validation of the relationship between a loss of EPCAM expression and MSH2-deficient Lynch syndrome CRCs. In the present study, we investigated the expression statuses of EPCAM and MMR proteins using IHC in 168 MSI-H CRC tissues obtained from Korean patients. Promoter CpG island methylation status of the MLH1 gene was also determined for each sample. Association of alterations in EPCAM expression with various clinicopathological and molecular factors was analyzed.