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Gene copy number aberrations are involved in oral squamous cell carcinoma (OSCC) development. To delineate candidate genes inside critical chromosomal regions, array-CGH was applied to 40 OSCC specimens using a microarray covering the whole human genome with an average resolution of 1 Mb. Gene copy number gains were predominantly found at 1q23 (9 cases), 3q26 (11), 5p15 (13), 7p11 (7), 8q24 (17), 11q13 (15), 14q32 (8), 19p13 (8), 19q12 (7), 19q13 (8), and 20q13 (9), whereas gene copy number losses were detected at 3p21-3p12 (15), 8p32 (11), 10p12 (8), and 18q21-q23 (10). Subsequent mRNA expression analyses by quantitative real time polymerase chain reaction found high mRNA expression of candidate genes SOX2 in 3q26.33, FSLT3 in 19p13.3, and CCNE1 in 19q12. Tissue microarray (TMA) analyses in a representative OSCC collection found gene copy number gain for SOX2 in 52% (115/223) and for CCNE1 in 31% (72/233) of the tumors. Immunohistochemical analyses on TMA sections of the corresponding proteins detected high expression of SOX2 in 18.1% (49/271) and of CyclinE1 in 23.3% (64/275) of tumors analyzed. These findings indicate that SOX2 and CCNE1 might be activated via gene copy number gain and participate in oral carcinogenesis. The combination of array-CGH with TMA analyses allows rapid pinpointing of novel promising candidate genes, which might be used as therapeutic stratification markers or target molecules for therapeutic interference.

Background: Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC. Methods: Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC). Results: Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.

Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC.Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC).Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P0.001). By contrast, specific TERT amplifications were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P = 0.047).High hTERT expression is a frequent finding in OSCC. It might be a promising target for the development of specific anti-neoplastic therapy approaches.

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.