It is known that the signal transducer and activator of transcription 3 (STAT3) is a key signaling molecule implicated in the regulation of growth and malignant transformation. Constitutive activation of STAT3 has been observed in a number of tumour-derived cell lines, as well as in a wide variety of human malignancies. The present study was conducted to examine p-STAT3 (activated form of STAT3) expression and its association with clinicopathological factors and prognosis in human colorectal adenocarcinomas. Expression of p-STAT3 was immunohistochemically examined in 108 cases of colorectal adenocarcinoma tissue obtained at surgery. and was found in 57.4% of tumours (62 of 108). p-STAT3 immunoreactivity significantly correlated with the depth grading of tumour invasion (p<0.001), lymphatic invasion(p<0.05), Dukes' classification (p<0.05), stage (p<0.001) and prognosis after operation (p<0.001). Expression of p-STAT3 was a marker of poor prognosis in overall survival (p<0.01). Expression of p-STAT3 was detected by Western blot analysis in three colon carcinoma tissue samples obtained at surgery.To our knowledge, this is the first study on the poor prognosis of p-STAT3 in human colorectal adenocarcinomas. These findings suggest that expression of p-STAT3 is an important factor related to tumour invasion and poor prognosis of human colorectal adenocarcinoma.

Background: The signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule implicated in the regulation of growth and malignant transformation. Constitutive activation of STAT3 is seen in several tumour derived cell lines, and in a wide variety of human malignancies. Aims: To examine the relation between p-STAT3 (activated form of STAT3) expression and clinicopathological factors in human colorectal adenocarcinoma and adenoma. Methods: Immunohistochemical analyses were carried out on tissues from 44 colorectal adenomas and 95 colorectal adenocarcinomas, comprising 18 intramucosal carcinomas and 77 invasive carcinomas. Results: Seventy seven of these 139 samples (55.4%) showed immunoreactivity for p-STAT3. Positive staining for p-STAT3 was seen in 69 of the 95 carcinomas. Only eight of the 44 adenomas showed immunopositivity for p-STAT3, resulting in a significant difference between total adenocarcinomas and adenomas (p , 0.001). Among the 95 cases of colorectal adenocarcinoma, p-STAT3 immunoreactivity was significantly correlated with the depth of tumour invasion (p , 0.05), venous invasion (p , 0.05), lymph node metastasis (p , 0.05), and increasing stages of the Dukes' classification (p , 0.01). Expression of p-STAT3 was detected by Western blot analysis in two different cultured human colorectal carcinoma cell lines and six colon carcinoma tissue samples obtained at surgery.

Previous investigations have shown that interleukin (IL)-11/IL-11 receptor ·-chain (IL-11R·), a member of the PI3K, MAPK and JAK-STAT activating family of cytokines/ receptors, correlates with the regulation of tumor progression. In this study, we established the IL-11/IL-11R· expression profile in human colorectal adenocarcinoma (CRC) and clarified its signaling pathway and role in the invasion activity of CRC cell lines. To elucidate the role of IL-11/ IL-11R·, we examined 103 cases of CRC and 24 cases of colorectal adenoma by immunohistochemistry. In addition, we investigated the invasive activity of cell signaling pathway of CRC cell lines. The IL-11R· expression was correlated with tumor invasion and lymphatic infiltration (p<0.01, respectively). Recombinant human IL-11 (rhIL-11) promoted the migration and proliferation of HT-29 cells and activated the PI3K and p44/p42 MAPK pathways. Wortmannin, a PI3K inhibitor, and PD98059, a p44/p42 MAPK inhibitor, significantly reduced the promotion of invasion and proliferation activity by rhIL-11, respectively. In summary, the IL-11R· expression was correlated with clinicopathological features and IL-11 promoted the invasion via the PI3K and up-regulated the proliferation via the p44/p42 MAPK in CRC cells. These findings suggested that the IL-11/IL-11R pathway plays an important role in the progression of CRC.

IL-11 and IL-11Ra are highly expressed in human colorectal adenocarcinoma and the IL-11Ra expression is correlated with clinicopathological factors. These findings suggest that the expression of IL-11Ra is an important factor for the invasion of human colorectal adenocarcinoma.

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