Homogeneous EGFR amplification defines a subset of aggressive Barrett's adenocarcinomas with poor prognosis.

AIMS: The epidermal growth factor receptor (EGFR) is a tyrosine kinase (TK) involved in the tumour progression of many cancer types and may serve as an important therapeutic target (erlotinib, cetuximab). Heterogeneity of EGFR amplification and expression could represent a major drawback for anti-EGFR therapy. The aim of this study was performed to determine the potential impact of tumour heterogeneity on anti-EGFR therapy in Barrett's adenocarcinoma (BAC). METHODS AND RESULTS: Tissue microarray (TMA) sections of 112 BAC and 45 lymph node metastases were analysed for EGFR amplification and expression using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). A subset of 20 samples was also sequenced for EGFR exons 18-21 and Kirsten rat sarcoma viral oncogene homologue (KRAS) exons 2-3 mutations. EGFR amplification was seen in seven (6.25%) of 112 interpretable BAC and typically high-level with more than 10-20 EGFR copies per tumour cell (EGFR/centromere 7 ratio >3). EGFR amplification was associated with high pT, pN and poor prognosis (P = 0.0004). Identical EGFR amplification status was found in 29 primary tumours and 29 matched lymph node metastases. Moreover, FISH analysis of three to 16 large sections from all amplified BAC and corresponding lymph node metastases did not reveal any heterogeneity of EGFR amplification. No EGFR mutation but one KRAS mutation was found. CONCLUSION: The high level and homogeneity of EGFR amplification in primary tumours and metastases suggests the potential therapeutic utility of anti-EGFR drugs in BAC.

High Ki67 expression is an independent good prognostic marker in colorectal cancer.

AIMS: To correlate Ki67 expression with outcome in colorectal cancer (CRC). METHODS: Ki67 labelling index (Ki67LI) was analysed by immunohistochemistry on a tissue microarray containing 1800 CRCs. The results were compared with clinicopathological and molecular parameters. RESULTS: Ki67LI was considered low in 26.3%, moderate in 56.7% and high in 17.0% of 1653 interpretable CRCs. High Ki67 expression was associated with low tumour stage (p<0.0001) and nodal status (p=0.0315), but not with tumour grade (p=0.8639), histological tumour type (p=0.1542) or tumour localisation, and was an independent prognosticator of favourable survival (p=0.0121). High Ki67 expression was also significantly associated with high-level nuclear ß-catenin and p53 expression (p<0.0001 and p=0.0095, respectively). CONCLUSIONS: In summary, our data show that high Ki67 expression in CRCs is associated with good clinical outcome. Ki67, p53 and ß-catenin overexpression seem to be linked to CRC, and indicate a cellular state of high proliferative activity. Finally, our findings strongly argue for a clinical utility of Ki67 immunostaining as an independent prognostic biomarker in CRC.