In a recent work on CRC, similar to the current one, comparing fascin expression with Ki-67 immunostaining, a lack of direct association between the two markers was noted, indicating that the fascin upregulation do not correlate positively with cell proliferation (Hashimoto et al, 2006). However, the prognostic role of the Ki-67-labelling index in colorectal carcinoma is still highly controversial and probably different from other solid neoplasms. colonic carcinoma cell lines increased the levels of neutral mucin (Jawhari extra-lymph Freselestat (ONO-6818) nodal colonisation). As fascin immunoreactivity is also associated with the number of metastatic lymph nodes and the occurrence of distant metastases, we hypothesise that this molecule is very likely involved in the metastatic process of colonic adenocarcinoma cells via its motility-inducing properties. This is further sustained by the observation that patients with lymph node metastases immunoreactive for fascin experienced a more aggressive clinical course than patients with negative lymph node metastases (Figure 4A). This significance was kept stratifying the prognostic impact of fascin according to tumour stages III and IV (Figure 4B). Thus, fascin expression in primary and metastatic tumours could unveil the different clinical aggressiveness of tumours that are otherwise classified in the same risk category. Fascin immunoreactivity was not associated with the tumour proliferation fraction as assessed by the Ki-67-labelling index, at variance with previous studies of lung and stomach cancers and also of colonic cell cultures (Jawhari et al, 2003; Pelosi et al, 2003b; Hashimoto et al, 2004). In a recent work on CRC, similar to the current one, comparing fascin expression with Ki-67 immunostaining, a lack of direct association between the two markers was noted, indicating that the fascin upregulation do not correlate positively with cell proliferation (Hashimoto et al, 2006). However, the prognostic role of the Ki-67-labelling index in colorectal carcinoma is still highly controversial and probably different from other solid neoplasms. In fact, recent observations document that a high Ki-67-labelling index is associated with better OS (Allegra et al, 2003) in both treated and untreated patients (Garrity et al, 2004), as reported in the current series (Table 2). Fascin immunoreactivity was associated with a shorter OS and DFS, independent of tumour stage, which is the most important prognostic factor in this tumour type (Compton and Greene, 2004). In the multivariate analysis, similar results were also obtained for other tumour types, such as pulmonary (Pelosi et al, 2003a), oesophageal (Hashimoto et al, 2005a), breast (Yoder et al, 2005) carcinomas and more recently CRC (Hashimoto et al, 2006). Our findings confirming that fascin is a negative prognostic factor for advanced colonic adenocarcinoma encourage clinical translation, especially when considering that the current substaging of colorectal cancer according to the latest TNM classification emphasizes Freselestat (ONO-6818) the prognostic heterogeneity of patients within the same tumour stage group. The different prognostic implications of lymph node metastases according to the amount of fascin could well be incorporated in new staging proposals. Finally, the identification of patients with a reduced life Freselestat (ONO-6818) expectation KPSH1 antibody according to the degree of fascin expressed by their respective tumours also justifies the potential use of novel targeted therapies, as recently proposed for other malignant epithelial neoplasms (Hashimoto et al, 2005b, 2006). Additional studies are needed to investigate the role of fascin in right-sided colonic cancer and in mucinous differentiation. Acknowledgments We thank Mrs Anna Maria Colussi for her assistance with editing and Mr Roberto Biancat for his help Freselestat (ONO-6818) in collecting data on patient’s survival. This work was supported by AIRC (Associazione Italiana per la Ricerca sul Cancro)..