H. Shiozaki et al., Clinical application of malignancy potential grading as a prognostic factor of human esophageal cancers, SURGERY, 127(5), 2000, pp. 552-561
Background. Various biologic markers have been reported to be prognostic fa
ctors in human esophageal cancers. In the current study, we established a n
ew tumor-grading system representing the malignancy potential of cancer cel
ls and compared it with the clinical-stage system.
Methods. Tumor samples from 77 patients with squamous cell carcinoma of the
esophagus were immunohistochemically evaluated for the expression of 10 mo
lecules: the cell cycle-related molecules of cyclin D1, Rb, p16(INK4), P27(
KIP1), and PCNA; the cell-cell adhesion molecules of E-cadherin, alpha-cate
nin, and beta-catenin; and the heat shock proteins of HSP27 and HSP70.
Results. p27(KIP1), beta-catenin, and HSP70 were selected for their high ha
zard ratio in multivariate analysis, and the number of their disordered mol
ecules was used to define the malignancy grade (MG). Five-year survival rat
es were 83%, 54%, 17%, and 0% for MG1, MG2, MG3, and MG4. The gradation of
survival curves was better for MGs than for clinical stages. MGs and clinic
al stages showed significant correlation; however; 55% of those in higher c
linical stages (stage 3 or 4) had lower MG (MG1 or 2) and showed better pro
gnosis than others in their group (stage 3 or 4 and MG3 or 4). The proporti
ons of shorter survival span to cancer death patients (less than I year) we
re 0%, 33%, 75%, and 100% in MG1, 2, 3, and 4, but the clinical stage was n
ot associated with the survival span.
Conclusions. The grading of malignancy potential is clinically useful, espe
cially for selecting patients who may show good prognosis in the advanced c
linical stage and for predicting short survival span. These predictions are
not possible with the clinical-stage system, which is based on the anatomi
c spread of cancer cells.