대장의 샘종, 샘암종에서 STAT3의 의의

Abstract

Colorectal adenocarcinoma is a major cause of morbidity and mortality in Western countries. By the way, it appears to have rapidly increased over the past two decades in Korea. The signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule that's been implicated in the regulation of cell growth and malignant transformation. To examine the relation between p-STAT3 (activated form of STAT3) expression and clinicopathologic parameters of human colorectal adenocarcinoma, we conducted immunohistochemical analyses on the formalin-fixed tissue from 127 colorectal adenocarcinomas, 10 colorectal adenomas and 10 normal colon mucosa specimens. To clarify the validity of the immunohistochemical expression of p-STAT3, quantitative real time-PCR were carried out on the fresh tissue samples from 51 colorectal adenocarcinomas, which were comprised of 4 intramucosal carcinomas and 47 invasive carcinomas and each of the corresponding normal colon mucosa specimens. Immunohistochemical analyses were conducted after formalin fixation of specimens from 51 adenocarcinoma cases to compare these results with the results of the real time-PCR. Ninety-six of these 127 adenocarcinomas (76%) showed immunoreactivity for p-STAT3. Only two of the 10 adenomas (20%) and none of the 10 normal mucosa specimens showed immunoreactivity for p-STAT3, resulting in a significant difference between the adenocarcinomas and adenomas (p=0.001), and between the adenocarcinomas and normal mucosa specimens (p=0.000). Among the 127 adenocarcinomas, p-STAT3 immunoreactivity was significantly correlated with the clinical stage, which were comprised of early and late stages (p=0.000) and nodal status (p=0.000). The intracytoplasmic expression of p-STAT3 was identified in 17 of 127 adenocarcinomas (13%), but not in the adenomas or normal mucosa specimens. This was significantly correlated with the clinical stage, which were comprised of early and late stages (p=0.004), nodal status (p=0.004) and survival length (p=0.018). Among the 51 adenocarcinomas, the result of real time-PCR was significantly correlated with the tumor size (p=0.023), M-stage (p=0.000) and clinical stage (p=0.036). The overall findings of the real time-PCR analyses were relatively very well correlated with the findings of the immunohistochemical analyses. These findings suggest that a p-STAT3 expression has an important role related to tumorigenesis and tumor progression of colorectal adenocarcinoma. Moreover, immunohistochemical analysis of the p-STAT3 expression is a reliable and useful modality to assess the p-STAT3 expression status in surgically resected formalin-fixed tissue samples.