DIFFERENT EXPRESSION OF TRANSFORMING-GROWTH-FACTOR BETA(1) IN PANCREATIC DUCTAL ADENOCARCINOMA AND CYSTIC NEOPLASMS

Pancreatic neoplasms harbor different prognoses according to their his tological type: a benign course for serous cystadenoma, a low malignan t potential for intraductal papillary mucinous neoplasms (IPMN), and h igh aggressiveness for ductal adenocarcinoma (ADC). Transforming growt h factor beta(1) (TGF beta(1)) may regulate tumor growth. The present study analyzes and compares the expression of its precursor beta(1)-la tency-associated peptide (beta(1)-LAP), its latent binding protein (LT BP), and its mRNA in ductal adenocarcinoma (n = 10), in IPMN (n = 8), in serous cystadenoma (n = 2), and in normal tissues (n = 5), LTBP is thought to play a strategic role in the processing and active secretio n of latent TGF beta(1) and its stockage in the extracellular matrix. Localization of beta(1)-LAP and LTBP was assessed by immunohistochemis try using specific antibodies and expression of TGF beta(1) mRNA by re verse-transcriptase polymerase chain reaction analysis. beta(1)-LAP wa s only slightly expressed in normal specimens, while LTBP was not dete cted. beta(1)-LAP was detected in the cytoplasm of neoplastic cells in 9 of 10 patients with ADC. An intense staining was present in stromal cells surrounding the neoplastic glands in all cases except in one ca rcinoma in situ. LTBP was detected only in stromal cells and in the su rrounding extracellular matrix. In IPMN with mild-grade dysplasia and in cystadenoma, beta(1)-LAP was strongly expressed in the epithelial c ells, while it was poorly detected in invasive IPMN; stromal cells wer e poorly or not all stained by beta(1)-LAP, except in invasive IPMN (n = 2). LTBP was detected in neoplastic cells of three cases with benig n IPMN and two of two cases with cystadenoma, while stroma was not imm unostained. TGF beta(1) mRNA was strongly expressed in most of the tum ors and no difference in expression was observed between the different types of neoplasms. There is no quantitative difference in expression of TGF beta(1) in ADC and in IPMN or cystadenoma. However, the latter are able to secrete TGF beta(1) efficiently, in contrast to ductal AD C as shown by the ability of the neoplastic cells to express both beta (1)-LAP and LTBP. Invasive stroma reaction was associated with enhance d beta(1)-LAP and LTBP expression in stromal cells and could be mediat ed by TGF beta(1) via LTBP.