A new formula for predicting liver metastasis in patients with colorectal cancer: immunohistochemical analysis of a large series of 439 surgically resected cases.
OBJECTIVE
The purpose of this study was to establish a new formula predicting liver metastasis in patients with colorectal cancer (CRC).


METHODS
Nine previously reported predictive markers for liver metastasis and/or prognosis (COX-2, dysadherin, E-cadherin, beta-catenin, Ki-67, p53, laminin5gamma2, matrilysin and MUC-1) were immunohistochemically investigated in 439 consecutive patients with CRC. We tried to determine the combination of molecules which best predicted liver metastasis. A formula for predicting liver metastasis was constructed using a training cohort comprising 150 cases, and applied to a validation cohort comprising 190 cases and another comprising 99 cases from an outside hospital.


RESULTS
A combination of dysadherin, E-cadherin and matrilysin was identified to be best for predicting liver metastasis (area under the curve value, 0.807). The predictive formula: 3x dysadherin score [0 for low expression (</=50% of tumor cells positive) or 1 for high expression (>50%)] + 4x E-cadherin score [0 for preserved (>80% of tumor cells positive) or 1 for reduced (</=80%)] + 2x matrilysin score [0 for low expression (</=30% of tumor cells positive) or 1 for high expression (>30%)] was able to discriminate patients with liver metastasis in the training cohort with a sensitivity of 85.7% and a specificity of 58.9%. The discriminative capacity of the formula was validated in the first cohort with a sensitivity of 87.0% and a specificity of 66.5%, and in the second cohort with a sensitivity of 80% and a specificity of 60.0%.


CONCLUSIONS
We have established a formula for predicting liver metastasis in patients with CRC, and confirmed that it has a high sensitivity potentially useful for clinical application.
Ochiai
Hiroki
H
Divisions of Pathology, National Cancer Center Research Institute and Hospital, Tokyo, Japan.
Nakanishi
Yukihiro
Y
Fukasawa
Yuri
Y
Sato
Yasunori
Y
Yoshimura
Kimio
K
Moriya
Yoshihiro
Y
Kanai
Yae
Y
Watanabe
Masahiko
M
Hasegawa
Hirotoshi
H
Kitagawa
Yuko
Y
Kitajima
Masaki
M
Hirohashi
Setsuo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D011237:Predictive Value of Tests
D014408:Biomarkers, Tumor; D015820:Cadherins; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7