Predicion of Metachronous Liver Metastasis on Curatively Resected Colorectal Cancer by Immunohistochemical Staining of p53, c-erbB-2, PCNA, CD44, and nm23

Fumichika Kitamura, Shigetoyo Saji, Daizo Fukada, Kiichi Miya, Katsuyuki Kunieda, Yasuyuki Sugiyama, Hiroshi Takao, Motohisa Katoh

Second Department of Surgery, Gifu University, School of Medicine

For the purpose of prediction of metachronous liver metastasis on curatively resected colorectal cancer, immunohistochemical expression of p53, c-erbB-2, CD44, nm23 and proliferating cell nuclear antigen labeling index (PCNA LI) was compared between 33 cases with metachronous liver metastasis (metachronous group) and 66 cases without liver metastasis (control group). Control group was frequency (1:2) matched with metachronous group for tumor location, depth of invasion, and histological typing. PCNA LI (p=0.0070), CD44 positive late (p=0.0033) and nm23 negative late (p=0.0227) of metachronous group were significantly higher than those of control group. Receiver operating characteristic (ROC) curve of PCNA LI indicated that the most compatible cut off value for liver metastasis was 60. On the other hand, expression of p53 or c-erbB-2 showed no correlations with metastasis. On metachronous group, CD44 positive cases had significantly shorter disease free intervals (DFI) than negative cases (p=0.0128), and nm23 negative cases had relatively shorter DFI than positive cases (p=0.0737). Cumulative survival of CD44 positive cases was relatively lower (p=0.0636) than that of negative cases. PCNA LI≥60 cases had the highest positive predictive value (PV-pos) on one test (0.23), and PCNA LI≥60 and nm23 negative cases showed the highest one on two tests (0.62) for liver metastasis. From above results it is suggested that immunohistochemical expression of CD44, nm23 and PCNA LI is useful for prediction of metachronous liver metastasis on curatively resected colorectal cancer.

Key words
metachronous liver metastasis of colorectal cancer, immunohistochemical stain, case control study, positive predictive value, receiver operating characteristic curve

Reprint requests
Fumichika Kitamura Second Department of Surgery, Gifu University, School of Medicine
40 Tsukasamachi, Gifu, 500 JAPAN

Accepted
November 13, 1996

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