epidermal-growth-factor and Cystadenocarcinoma--Mucinous

The pancreatic cystic neoplasms, including solid pseudopapillary tumour (SPT), mucinous cystic neoplasm (MCN), and intraductal papillary mucin producing tumour (IPMT), have their characteristic clinicopathological features. A systematic investigation of oestrogen receptor (OR), progesterone receptor (PR), trefoil factor 1(TFF1), and epidermal growth factor and its receptor (EGF and EGFR) expressed in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma was determined to elucidate their corresponding sex and age predilection, cell origin, and pathway of malignant transformation.. Surgical specimens of SPT (n=10), MCN (n=12), IPMT (n=10), and ductal adenocarcinoma (n=20) were studied. The expression of OR, PR, TFF1, EGF, and EGFR were each determined in each disease entity using monoclonal antibodies by immunohistochemical method. The results were correlated with the clinicopathological data.. PR was expressed in all 10 SPT, whereas OR was expressed in none of 10 SPT. TFF1 was not or weakly expressed in SPT. Although EGF was strongly expressed in seven of 10 SPT, synchronous expression of EGF and its receptor was expressed in none of 10 SPT. Of the 12 MCN, six had PR expression in the stroma cells but not in the neoplastic epithelium, seven had a moderate or strong expression of TFF1, and 10 had no or weak EGFR expression, irrespective of their benigneity or malignancy. Synchronous expression of EGF and EGFR was observed in only one of 12 MCN. Among 10 IPMT, TFF1 and EGFR were moderately or strongly expressed in all six malignancies, whereas TFF1 and EGFR were not or weakly expressed in three of four benigneity. Of 20 ductal adenocarcinomas, TFF1 and EGFR were moderately or strongly expressed in 16 and 12, respectively. Synchronous expression of EGF and EGFR was observed in six of 10 IPMT and nine of 20 ductal adenocarcinoma, respectively.. PR was uniquely expressed in SPT, and OR and PR were expressed in stroma of MCN, reflecting their sex and age predilection. TFF1 expression was related to EGFR such as in IPMT and ductal adenocarcinoma, not related to EGFR such as in MCN, and not related to hormonal receptors such as in SPT. EGF and its receptor might play a part in the malignant transformation of IPMT and ductal adenocarcinoma, but not of SPT and MCN.

Topics: Adult; Aged; Cystadenocarcinoma, Mucinous; Epidermal Growth Factor; ErbB Receptors; Female; Growth Substances; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Proteins; Pancreatic Neoplasms; Peptides; Proteins; Receptors, Cell Surface; Receptors, Estrogen; Receptors, Progesterone; Trefoil Factor-1; Tumor Suppressor Proteins

Elevated levels of the growth factor pS2 protein in the cyst fluids of mucinous cystic tumors correlate with earlier observations using immunohistochemical techniques showing that pS2 protein is expressed by these tumors. The markedly elevated levels of pS2 protein compared to normal plasma values suggest that this growth factor may be important in the pathogenesis of pancreatic mucinous cystic tumors.. Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors, some of which are malignant. Previous studies using immunohistochemical techniques have shown that virtually all pancreatic mucinous tumors express pS2 protein. pS2 protein is a growth factor that is believed to be important in the normal process of inflammation and repair. We measured pS2 protein and other growth factors in pancreatic cyst fluids to assess their potential pathophysiologic and diagnostic significance.. Levels of pS2 protein were measured in 54 pancreatic cyst fluids by radioimmunoassay. The growth factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factors I and II (IGF-I, IGF-II) were measured in 22 cyst fluids using commercial immunoassays.. Mucinous cysts exhibited significantly higher levels of cyst fluid pS2 protein than nonmucinous lesions, including pseudocysts and serous cystadenomas (median: 78,303 pg/mL; range: 218-361,176 pg/mL vs median: 886 pg/mL; range: 0-14,206 pg/mL; p = 0.0001). The level of pS2 in mucinous tumors was markedly higher than plasma values (median: 392 pg/mL). Levels of pS2 protein in malignant mucinous lesions tended to be higher than those in benign mucinous cysts, but this difference was not statistically significant (median: 88,817 vs 64,350 pg/mL; p = 0.159). Levels of other growth factors, including EGF, TGF-alpha, IGF-I, and IGF-II, did not discriminate among the different cyst types, and the values were within normal plasma ranges.

Topics: Cyst Fluid; Cystadenocarcinoma, Mucinous; Cystadenoma, Mucinous; Cystadenoma, Serous; Epidermal Growth Factor; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Pancreatic Cyst; Pancreatic Neoplasms; Pancreatic Pseudocyst; Proteins; Transforming Growth Factor alpha; Trefoil Factor-1; Tumor Suppressor Proteins

Effects of sex steroids (estradiol-17 beta, E2; progesterone, Prog) and growth factors (epidermal growth factor, EGF; transforming growth factor-alpha, TGF-alpha) on invasive activity and 5'-deoxy-5-fluorouridine (5'-dFUrd) sensitivity of ovarian adenocarcinoma OMC-3 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were inhibited by 10 microM Prog, but stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. E2 did not have any effect on tumor cell migration or invasion. The zymography of tumor conditioned medium showed that the treatment of OMC-3 cells with EGF and TGF-alpha resulted in increases of type IV collagenase, stromelysin and urokinase-type plasminogen activator (uPA). EGF and TGF-alpha up-regulated thymidine phosphorylase (dThdPase) expression of tumor cells and consequently enhanced the antiproliferative action of 5'-dFUrd, which is converted to 5-fluorouracil by dThdPase. E2 and Prog did not have significant effects on the expression of proteolytic enzymes and dThdPase, or on the 5'-dFUrd sensitivity of tumor cells. The inhibitory effect of Prog on tumor cell invasion may depend on its inhibitory action on the motility of tumor cells. These results suggest that EGF and TGF-alpha simultaneously up-regulate the potential of ovarian adenocarcinoma cells to invade extracellular matrices and their dThdPase expression, both of which are associated with the specific action of 5'-dFUrd selectively to kill tumor cells with high invasive and metastatic potential.

Topics: Basement Membrane; Cell Division; Cell Movement; Collagenases; Culture Media, Conditioned; Cystadenocarcinoma, Mucinous; Drug Resistance, Neoplasm; Enzyme Induction; Epidermal Growth Factor; ErbB Receptors; Estradiol; Female; Fibronectins; Floxuridine; Humans; Matrix Metalloproteinase 3; Neoplasm Invasiveness; Neoplasm Proteins; Ovarian Neoplasms; Prodrugs; Progesterone; Receptors, Estrogen; Receptors, Progesterone; Thymidine Phosphorylase; Transforming Growth Factor alpha; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator

The importance of epidermal growth factor (EGF) receptor-dependent growth has not been clarified for in vivo growth of primary human ovarian cancers.. Seventeen primary human ovarian cancer tissue samples were examined for the presence of EGF receptors by a 125I-EGF-binding study. Three groups of mice were inoculated with EGF receptor expressing and not-expressing cancer tissues. The groups were as follows: control group, Sx group (mice that underwent sialoadenectomy; EGF depleted mice), and Sx+EGF (EGF-replaced) group. The ability of the inoculated tissues to implant and grow then was studied.. Of the 17 primary ovarian cancers, 12 expressed EGF receptors and 5 did not. Eight of 12 EGF-receptor expressing cancer tissues implanted and formed growing tumors in control animals. None implanted in the Sx animals. Epidermal growth factor receptor-expressing cancers implanted in Sx animals that received EGF administration. Two of five EGF receptor-negative ovarian cancers implanted and grew in both control and Sx animals.. Growth of EGF receptor-expressing primary human ovarian cancers may be dependent on EGF in vivo.

Topics: Animals; Base Sequence; Cell Membrane; Cystadenocarcinoma, Mucinous; Cystadenocarcinoma, Serous; Epidermal Growth Factor; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Humans; Iodine Radioisotopes; Mice; Mice, Nude; Molecular Sequence Data; Neoplasm Transplantation; Ovarian Neoplasms; Polymerase Chain Reaction; Protein Binding; RNA, Neoplasm; Salivary Glands; Transcription, Genetic; Transforming Growth Factor alpha; Transplantation, Heterologous; Tumor Cells, Cultured