Induction of ductal and stromal hyperplasia by basic fibroblast growth factor produced by human pancreatic carcinoma.
A histopathology study of 22 pancreatic adenocarcinoma cases revealed that 13 of the patients presented with hyperplastic lesions (atypical and non-atypical hyperplasia, mucous cell hypertrophy, focal epithelial hyperplasia, and ductal papillary hyperplasia), and 9 exhibited fibrosis adjacent to the carcinoma. All lesions expressed high levels of epidermal growth factor receptor (EGF-R) (p<0.0001 and p=0.0008, respectively) as compared with normal ductal epithelium. Non-atypical and atypical hyperplastic lesions also had a higher proliferating cell nuclear antigen (PCNA) labeling index (p<0.001 and p=0.0008, respectively) than normal ductal epithelium. A gradient in PCNA+ nuclei was found in acinar cells adjacent to the tumors. In 16 cases with marked fibrosis, we observed a significant increase of PCNA+ nuclei in stromal fibroblasts (p=0.0041) and significant upregulation of basic fibroblast growth factor (bFGF) mRNA expression in adjacent tumor cells (p=0.0213). These data suggest that the production of bFGF by pancreatic cancer cells induces ductal and stromal hyperplasia of the pancreas.
Kuniyasu
H
H
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Abbruzzese
J L
JL
Cleary
K R
KR
Fidler
I J
IJ
D000230:Adenocarcinoma / Q000378:metabolism* / Q000601:surgery; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D006965:Hyperplasia; D017403:In Situ Hybridization; D008940:Mitotic Index; D009367:Neoplasm Staging; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000473:pathology
D017931:DNA Primers; D015342:DNA Probes; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2