Association of epidermal growth factor-related peptides and type I receptor tyrosine kinase receptors with prognosis of human colorectal carcinomas.
The frequency of expression and localization of cripto-1 (CR-1), amphiregulin (AR), transforming growth factor alpha (TGF alpha), 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 alpha, 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-alpha, EGFR and erbB-2, respectively. There was a statistically significant association between the frequency of either TGF alpha (P < 0.05) or erbB-2 (P < 0.05) expression and lymph node metastasis. In addition, a significantly higher frequency of positive staining for TGF alpha was observed in Dukes' grade C carcinomas (P < 0.05). Finally, significant trends for coexpression of EGFR and either TGF alpha (P < 0.01) or AR (P < 0.05) were detected in carcinomas. These data suggest that AR and TGF alpha may play an important role in the development of colorectal carcinomas through an autocrine mechanism involving EGFR, and demonstrate that TGF alpha and erbB-2 may be more reliable indicators of metastasis or prognosis than CR-1, AR or EGFR in human colon cancers.
Saeki
T
T
Department of Clinical Research, Pathology and Surgery, National Shikoku Cancer Center Hospital, Matsuyama.
Salomon
D S
DS
Johnson
G R
GR
Gullick
W J
WJ
Mandai
K
K
Yamagami
K
K
Moriwaki
S
S
Tanada
M
M
Takashima
S
S
Tahara
E
E
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D066258:Amphiregulin; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D066258:Amphiregulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; C587848:AREG protein, human; C070636:TDGF1 protein, human