RESUMO
BACKGROUND: Little is known about the factors that drive metastasis formation in colorectal cancer (CRC). Here, we set out to identify genes and proteins in patients with colorectal liver metastases that correlate with early disease recurrence. Such factors may predict a propensity for metastasis in earlier stages of CRC. METHODS: Gene expression profiling and proteomics were used to identify differentially expressed genes/proteins in resected liver metastases that recurred within 6 months following liver surgery vs those that did not recur for >24 months. Expression of the identified genes/proteins in stage II (n=243) and III (n=176) tumours was analysed by immunohistochemistry on tissue microarrays. Correlation of protein levels with stage-specific outcome was assessed by uni- and multivariable analyses. RESULTS: Both gene expression profiling and proteomics identified Maspin to be differentially expressed in colorectal liver metastases with early (<6 months) and prolonged (>24 months) time to recurrence. Immunohistochemical analysis of Maspin expression on tumour sections revealed that it was an independent predictor of time to recurrence (log-rank P=0.004) and CRC-specific survival (P=0.000) in stage III CRC. High Maspin expression was also correlated with mucinous differentiation. In stage II CRC patients, high Maspin expression did not correlate with survival but was correlated with a right-sided tumour location. CONCLUSION: High Maspin expression correlates with poor outcome in CRC after spread to the local lymph nodes. Therefore, Maspin may have a stage-specific function possibly related to tumour cell dissemination and/or metastatic outgrowth.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Serpinas/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/genética , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Serpinas/genéticaRESUMO
AIMS: The aim of this study was to evaluate the oncological outcome of portal triad clamping during hepatectomy in colorectal cancer patients. METHODS: 160 patients with colorectal liver metastases underwent a partial hepatectomy with curative intent. Data were collected in a prospective database and were retrospectively analyzed for time to liver recurrence (TTLiR) and time to overall recurrence (TTR). The prognostic significance of portal triad clamping of any type and severe ischemia due to prolonged portal triad clamping was determined by Cox regression models. RESULTS: TTLiR was reduced after clamping of any type, although not statistically significant (p=0.061). Severe ischemia due to prolonged portal triad clamping significantly decreased TTLiR (p=0.022), but not TTR. Furthermore, severe ischemia independently predicted TTLiR in a multivariable analysis (p=0.038). CONCLUSIONS: Severe ischemia due to prolonged portal triad clamping during hepatic resection for colorectal liver metastases appears to be associated with decreased TTLiR. Further research remains necessary to determine the causative effect of prolonged vascular clamping on liver tumour recurrence.
