Expression of the signal transducer and activator of transcription factor 3 and Janus kinase 3 in colorectal carcinomas, colonic adenomas and ulcerative colitis

Mohamed M Shareef; Maha M Shamloula; Asem A Elfert; Mohamed El-Sawaf; Hanan H Soliman

doi:10.1016/j.ajg.2009.03.006

Expression of the signal transducer and activator of transcription factor 3 and Janus kinase 3 in colorectal carcinomas, colonic adenomas and ulcerative colitis

Arab J Gastroenterol. 2009 Mar;10(1):25-32. doi: 10.1016/j.ajg.2009.03.006. Epub 2009 May 3.

Authors

Mohamed M Shareef¹, Maha M Shamloula¹, Asem A Elfert², Mohamed El-Sawaf³, Hanan H Soliman⁴

Affiliations

¹ Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.
² Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: asemelfert@asemelfert-ddc.com.
³ Department of Surgery, Faculty of Medicine, Tanta University, Tanta, Egypt.
⁴ Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt.

PMID: 24842133
DOI: 10.1016/j.ajg.2009.03.006

Abstract

Background and study aims: Despite the growing understanding of the involvement of protooncogenes and tumour suppressor genes in the oncogenesis of CRC, the exact biological and molecular mechanisms underpinning this process remain poorly understood. The signal transducer and activator of transcription (STAT3) has been implicated in the regulation of growth and malignant transformation. Accumulating evidences have come to indicate that abnormalities in the Janus kinase (JAK)/STAT pathway are involved in oncogenesis of several cancers. The aim of this study was to investigate the expression of JAK3 and STAT3 in both normal and activated forms by immunohistochemistry in adenomas of the colon, ulcerative colitis and CRC compared to normal colonic mucosa.

Patients and methods: Tissues from 30 cases with primary CRC and seven cases with ulcerative colitis (UC), removed by colectomy, were included. In addition, tissues from 10 colonic adenomas, 15 CRC and eight cases with UC, obtained by endoscopic biopsies, were examined histopathologically. Immunohistochemical evaluation of STAT3, p-STAT3, JAK3 and p-JAK3 expression in tissue sections was completed. Statistical analysis and correlation of data were then performed.

Results: Normal colonic mucosa showed expression of STAT3 only. Immunoreactivity of p-JAK3 increased significantly (p<0.05) and correlated with the degree of dysplasia in colonic adenomas. Immunoreactivity of p-STAT3 increased significantly (p<0.05) and correlated with the degree of dysplasia in cases with UC. In CRC a significant positive correlation was found between p-STAT3 expression and grading, STAT3, JAK3 and p-JAK3 and TNM or Dukes' staging, and p-STAT3 and nodal status excluding distant metastasis (p<0.05).

Conclusion: JAK3 and STAT3, and particularly their activated forms, were found to correlate significantly with the degree of dysplasia in adenomas and UC, indicating their potential role in colorectal carcinogenesis. They also correlate with anaplasia and invasion, suggesting a definitive role in progression of CRC.

Keywords: Colonic adenomas; Colorectal carcinoma; Immunohistochemistry; JAK3; STAT3; Ulcerative colitis.