Prognostic implication of proliferative markers MIB-1 and PC10 in esophageal squamous cell carcinoma

Abstract

BACKGROUND. Proliferative markers are related to tumor behavior. The commonly used markers are proliferating cell nuclear antigen (PCNA) and Ki- 67. The aim of this study is to evaluate the usefulness of MIB-1 (for Ki-67) and PC10 (for PCNA) in the assessment of the clinicopathologic features and prognosis in patients with esophageal squamous cell carcinoma. METHODS. One hundred patients (88 males, 12 females; mean age, 63 years [range, 39 to 83 years]) with surgically resected esophageal squamous cell carcinoma (32 well differentiated, 51 moderately differentiated, and 17 poorly differentiated) were studied. The clinicopathologic features and survival data of these patients were noted. Representative tissue was collected from each tumor and immunohistochemical preparations for MIB-1 and PC1O were made. RESULTS. The percentages of cells that tested positive for PC10 and MIB-1 were much higher in tumor cells than in nonneoplastic cells. The pattern of expression of both markers varied with the differentiation of the tumor. The results observed with MIB-1 staining were better than those with PC10; because MIB-1 had less background staining, as well as stronger and more uniform positive signals corn pared with PC10. Thus, further investigation was performed on MIB-1- stained sections. The tumor cell MIB-1 scores ranged from 169 to 964 positive cells per 1000 cells (mean 598 ± 211; median, 636). Although it was significantly associated with the differentiation of the tumor (P = 0.0001), the score had no significant relationship to the tumor size, location, or stage, or to the patients' age and sex. The prognosis depended on the size and stage of the lesion. In Stage III lesions (n = 83), patients with MIB-1 scores below 300 had longer actual survival rates than those with a score of 300 or above. However, the survival rates of patients in the latter group were better if the greatest dimension of the tumor diameter was 7.5 cm or less. CONCLUSIONS. Proliferative activity in esophageal squamous cell carcinoma, as defined by the MIB-1 immunohistochemical method, is significantly related to tumor differentiation. It is also potentially valuable as a prognostic marker in addition to its use in tumor staging and size.