Comparative study of various biological parameters, including expression of survivin, between primary and metastatic human colonic adenocarcinomas.
BACKGROUND
Hepatic metastasis of colorectal carcinomas is the most important factor in prognosis. We examined the level of apoptosis and proliferation, the expression of survivin, bcl-2, p53 and intratumoral microvessel density (IMVD) in paired tissue specimens of primary human colon tumors and hepatic metastases and determined the molecular biological changes of the tumor cells in liver metastasis.


METHODS
We examined, immunohistochemically, the level of apoptosis and proliferation, the expression of survivin, bcl-2 p53 and intratumoral microvessel density in 37 paired tissue specimens of primary colon tumors and hepatic metastases.


RESULTS
The mean apoptotic index (AI) was 0.60+/-0.45 for the primary colon tumors and 1.22+/-0.73 for the hepatic metastases. The mean proliferative index (PI) was 37.4+/-15.8 for the primary colon tumors and 29.4+/-14.1 for the hepatic metastases. Significantly higher AI and lower PI were observed in the hepatic metastases as compared to the primary colon tumor (p<0.0001 and p=0.0049, respectively). The mean-weighted survivin score was 4.32+/-2.78 for primary colon carcinomas, and 1.54+/-1.77 for the hepatic metastases. The mean-weighted bcl-2 score was 2.62+/-2.62 for the primary colon carcinomas and 0.81+/-1.56 for the hepatic metastases. There were significantly decreased scores of immunostaining for both survivin and bcl-2 in the hepatic metastases as compared to the primary carcinomas (p<0.0001 and p<0.0002, respectively). Nuclear accumulation of p53 was demonstrated in 25 cases (67.6%) of the primary carcinomas and 24.cases (64.9%) of the hepatic metastases, without significant differences. The IMVD was 89.9+/-37.5 for primary colon tumors, while it was 55.1+/-32.5 for hepatic metastases. A statistically significant decrease in the IMVD was observed in the hepatic metastases as compared to the primary colon tumors (p<0.0001).


CONCLUSIONS
These data suggest that the tissue kinetics of colorectal carcinoma cells in hepatic metastases are biologically quite different from those of primary tumors, probably because of co-operative effects of both internal (AI, survivin, bcl-2) and external (IMVD) regulation factors.
Agui
Tomoyuki
T
Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Japan.
McConkey
David J
DJ
Tanigawa
Nobuhiko
N
D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53