Better survival in women with resected hepatocellular carcinoma is not related to tumor proliferation or expression of hormone receptors

Abstract

Objective: There is a well known male predominance in hepatocellular carcinoma (HCC). Moreover, female patients with HCC have better survival and lower recurrence rates after surgical resection. We previously showed that the better prognosis in female patients is related to a higher incidence of tumor encapsulation and less invasive tumors. However, the underlying mechanism is still obscure. Methods: In this study, we examined the cell proliferative indices (expression of proliferative cell nuclear antigen (PCNA) and Ki-67 antigen using MIB1 antibody) and expression of the estrogen and progesterone receptors (ERs and PRs, respectively)in 71 patients with resected HCC. These were correlated with the pathological features of the tumors and the survival rates of patients. Results: Female patients with HCC had significantly better actuarial and disease-free survival rates than male patients (p = 0.010 and 0.004, respectively). Tumor PCNA scores, represented by positively stained nuclei per 1000 tumor cells, were significantly higher in tumors showing venous permeation (p = 0.034), positive resection margins (p = 0.011), and absence of bile production (p = 0.008). Higher tumor MIB1 scores were seen in tumors that had poorer cellular differentiation (p = 0.002) and no tumor capsules (p = 0.042). However, both tumor PCNA and MIB1 scores did not differ significantly between female and male patients. ERs were detected in the tumor cells in 23.9% of tumors, and PRS were detected in 14.3%. Expression of both ER and PR was not influenced by gender. Conclusions: Women with HCC had significantly better survival and lower tumor recurrence rates. However, significant differences in cellular proliferation indices and expression of ER and PR were not observed between men and women to explain the difference in survival rate.