Expression of pSTAT3 in human colorectal carcinoma: correlation with clinico-pathological parameters.

PURPOSE: Signal transducers and activators of transcription (STATs) are tyrosine phosphorylated transcription factors activated by the Jak family kinases. Various ligands, including interferons and growth factors induce activation of STATs. STATs are key signaling molecules in malignant transformation and tumor progression. Constitutive activation of the STAT3 has been observed in a wide variety of human malignancies. The purpose of this study was to evaluate the clinical significance of phosphorylated (p) STAT3 expression in human colorectal adenocarcinomas (CRC). METHODS: 135 primary human CRC were immunohistochemically studied, from which 11 were intramucosal and 124 invasive carcinomas. The observed pattern of pSTAT3 immunostaining was nuclear and cytoplasmic. Nuclear pSTAT3 staining was calculated as the number of pSTAT3 positive nuclei divided by the total number of nuclei in at least 10 fields, and then expressed as a percentage. Cytoplasmic positivity of pSTAT3 was measured, depending on the intensity of immunoreactivity and scored as mild, moderate and intense. RESULTS: Positive staining for pSTAT3 immunoreactivity was significantly correlated with the depth of tumor invasion (p<0.001), venous invasion (p<0.05), lymph node metastasis (p<0.05) and advanced Dukes stage (p<0.001). There was no significant correlation between pSTAT3 immunoreactivity and poor differentiation of CRC. CONCLUSION: The expression of pSTAT3 is an important factor related to tumor and vascular invasion, nodal involvement and advanced CRC stage.