The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to behave likea negative prognostic marker in stage I colorectal carcinoma. In the aim of clarifying whether its associationwith adverse outcome may descend from NGAL’s ability to regulate matrix metallo-proteinase-9(MMP-9), we analyzed the correlation, prognostic value, and association with neo-angiogenesis of NGALand MMP-9 immunohistochemical expression in a series of stage I colorectal carcinomas. A variableNGAL immunoexpression was demonstrated in 17 of the 48 analyzed cases with a significantly higherfrequency of positive cases among patients showing disease progression. NGAL expression was also positivelycorrelated with VEGF expression detected in the same cases. MMP-9 immunostaining was presentin the cytoplasm of the neoplastic cells in 30 cases; no significant correlations were evidenced with NGALexpression, as well as with the various clinico-pathological parameters or with progression of the colorectalcarcinomas. By contrast, NGAL expression was confirmed as a significant independent negativeprognostic marker related to a shorter disease-free survival in stage I colorectal carcinoma. Our preliminaryresults suggest that the association of NGAL with poor outcome might be independent from MMP-9regulation, thus highlighting its prognostic value in this neoplasia. If our findings are confirmed in furtheranalyses, NGAL assessment might be used in order to select those patients with a higher progression riskand to submit them to adjuvant therapies useful to prevent adverse outcome.

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