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Japanese Journal of Clinical Oncology 25:240-249 (1995)
© 1995 Foundation for Promotion of Cancer Research
Association of Epidermal Growth Factor-related Peptides and Type I Receptor Tyrosine Kinase Receptors with Prognosis of Human Colorectal Carcinomas
1 Department of Clinical Research, Pathology and Surgery, National Shikoku Cancer Center Hospital Matsuyama
2 Tumor Growth Factor Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute Bethesda, MD
3 Division of Cytokine Biology, Food and Drug Administration, National Institutes of Health Bethesda
4 Molecular Oncology Unit, Imperial Cancer Research Fund, Hammersmith Hospital London
5 Department of Pathology, School of Medicine, Hiroshima University Hiroshima
For reprints and all correspondence: Toshiaki Saeki, Department of Clinical Research, National Shikoku Cancer Center Hospital, 13 Horinouchi, Matsuyama 790
Received February 24, 1995; accepted July 3, 1995
The frequency of expression and localization of cripto-1 (CR-1), amphiregulin (AR), transforming growth factor alpha (TGF
), epidermal growth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistry in 45 carcinomas and adjacent non-involved normal colon mucosa. Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%) of the 45 carcinomas showed positive staining for CR-1, AR, TGF, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%), 15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involved normal mucosa specimens were reactive. Among 13 carcinomas with lymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8 (61.5%) and 7 (53.8%) exhibited positive staining for CR-1, AR, TGF-, EGFR and erbB-2, respectively. There was a statistically significant association between the frequency of either TGF (P<0.05) or erbB-2 (P<0.05) expression and lymph node metastasis. In addition, a signficantly higher frequency of positive staining for TGF was observedin Dukes' grade C carcinomas (P<0.05). Finally, significant trends for coexpression of EGFR and either TGF (P<0.01) or AR (P<0.05) were detected in carcinomas. These data suggest that AR and TGF may play an important role in the development of colorectal carcinomas through an autocrine mechanism involving EGFR, and demonstrate that TGF and erbB-2 may be more reliable indicators of metastasis or prognosis than CR-1, AR or EGFR in human colon cancers.
Key Words: Cripto-1 • Amphiregulin • Epidermal growth factor receptor • Transforming growth factor • erbB-2 • Colon neoplasm
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