Androgen Receptor and Ki67 Expression and Survival Outcomes in Non-small Cell Lung Cancer

Abstract

Lung cancer is the most common cause of cancer-related deaths worldwide with non-small cell lung cancer (NSCLC) making up most of these cases. Males have poorer overall survival compared to women following a lung cancer diagnosis. Many studies have focused on the effects of estrogen to explain higher survival rates among women, but few have looked at the effects of androgens. We describe the expression of the androgen receptor (AR) and Ki67 in lung cancer specimens in the Manitoba Tumor Bank (MTB) and correlate these factors with patient outcome. Using the MTB, we performed immunohistochemistry on lung cancer tissue to determine expression of the AR and Ki67. These were then correlated with patient outcome. Of the 136 cases, 55% were female and 55% were adenocarcinoma. AR expression was not independently associated with outcome. Ki67 was associated with a significantly higher hazard ratio for death and recurrence (HR 2.19, 95% CI 1.30-3.70; HR 1.92, 95% CI 1.07-3.46, respectively). AR expression modified the effect of Ki67 on outcome, such that when both were expressed, there was no association with recurrence or survival (HR 2.39, 95% CI 1.31-4.36 for AR- Ki67+ vs HR 1.54, 95% CI 0.44-5.37 for AR+ Ki67+). Ki67 was associated with poorer outcomes alone. AR status alone was not associated with outcome. Although the mechanism remains unclear, AR status seems to negate the association of a high Ki67 and poor outcome.

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“…Ki67 is expressed only in the nucleus of proliferating cells and reflects the proliferative activity of tumor cells. 9 Ki67 has been reported to be significantly upregulated in a variety of tumor tissues and cells, such as lung, 10 gastric, 11 colon, 12 ovarian, 13 and OS. 14 Our results are consistent with these reports.…”

A magic drug target: Androgen receptor

“…And such application has not been found at clinical trial for lung cancer. Nevertheless, sex hormones and their receptors including AR showed influence on lung cancer in a mouse model, and AR expression together with Ki67 expression are associated with the survival outcome of non‐small‐cell lung cancer . As for liver cancer, AR is overexpressed in about 37% of hepatocellular carcinoma tumors, and AR overexpression stimulates oncogenic growth .…”

“…Nevertheless, sex hormones and their receptors including AR showed influence on lung cancer in a mouse model, 148 and AR expression together with Ki67 expression are associated with the survival outcome of non-small-cell lung cancer. 149 As for liver cancer, AR is overexpressed in about 37% of hepatocellular carcinoma tumors, and AR overexpression stimulates oncogenic growth. 150 In addition, it is reported that androgen promotes the growth of hepatocellular cancer cells by upregulating the transcription factor activity of ETS-1.…”

Expression of female sex hormone receptors and its relation to clinicopathological characteristics and prognosis of lung adenocarcinoma

“…Berardi et al [35] demonstrated a better OS in female non-small cell carcinoma patients with AR expression in carcinoma cells compared to those with tumors showing no AR expression. In contrast, Grant et al [36] demonstrated that AR expression has no association with recurrence or survival in modification with the Ki-67 labeling index. In the present study, only one case expressed AR receptor positivity and therefore cannot be interpreted because of the small number.…”