Pancreatic duct cell carcinomas express high levels of high mobility groupI(Y) proteins

The high mobility group I (HMGI) family of proteins in mammals belongs to a group of nonhistone nuclear proteins known as architectural transcriptiona l factors. They function in vivo as both structural components of chromatin and auxiliary gene transcription factors. In an earlier study (N, Abe et n l., Cancer Res., 59: 1169-1174, 1999), we demonstrated that the expression level of the HMGI(Y) gene/proteins was significantly increased in colorecta l adenocarcinoma and colorectal adenoma with severe cellular atypia, In the current study, we analyzed HMGI(Y) expression in several human pancreatic lesions to investigate (a) whether HMGI(Y) overexpression is also observed in pancreatic carcinoma, and (b) the role of HMGI(Y) in the diagnosis of pa ncreatic neoplasms. To this end, HMGI(Y) expression was determined at the p rotein level by immunohistochemistry using a HMGI(Y)-specific antibody in 6 surgically resected specimens of nonneoplastic tissue (4 specimens of norm al pancreatic tissue and 2 specimens of chronic pancreatitis tissue), 8 pan creatic cystic neoplasms (5 intraductal papillary mucinous adenomas, 1 sero us cystadenoma, and 2 solid pseudopapillary tumors), and 15 duct cell carci nomas of the pancreas. Immunohistochemical analysis revealed intense nuclea r staining in the pancreatic carcinoma cells, whereas only very faint nucle ar staining was seen in the nonneoplastic cells. There was a strong correla tion between HMGI(Y) protein overexpression and a diagnosis of carcinoma (P = 0.000018). Thus, an increased expression level of the HMGI(Y) proteins w as clearly associated with the malignant phenotype in pancreatic tissue. In addition, a low level of protein expression was also apparent in two of th e cystic neoplasms that exhibited cellular atypia, but not in those that di d not exhibit cellular atypia, Based on these findings, we propose that the HMGI(Y) proteins could be closely associated with tumorigenesis in the pan creas and that HMGI(Y) could serve as a potential diagnostic molecular mark er for distinguishing pancreatic malignancies unambiguously from normal tis sue or benign lesions.