自1982年以來，肺癌分別高居台灣女性和男性癌症主要死因的第一位和第二位。雖然已知抽菸是導致肺癌的主要原因，但是對於非抽菸肺癌患者的致病因子仍尚未清楚。抽菸之外的其他的環境因子和台灣女性肺癌的發生有關。本研究室最近研究發現，人類乳突瘤病毒(human papillomavirus；HPV) 16/18的感染和不抽菸台灣女性肺癌的形成有關。先前研究報導指出，人類子宮頸癌細胞會產生高量的介白質-6 (interleukin-6；IL-6)，且HPV 16/18感染的子宮頸癌腫瘤組織會製造大量的IL-6；而經IL-6處理的子宮頸癌細胞可由PI 3-K/Akt/Mcl-1的路徑而有效地抑制子宮頸癌細胞走向細胞凋亡。我們在本研究試圖探討在肺腫瘤組織中，HPV16/18感染是否會和IL-6及Mcl-1的表現有所關聯。我們利用免疫組織化學染色(immunohistochemistry；IHC)偵測88個肺癌病患的肺腫瘤組織中IL-6及Mcl-1的表現，發現IL-6及Mcl-1的陽性表現率分別是68％及56％。統計分析的結果顯示，IL-6的表現和腫瘤的分期有顯著的相關(p=0.043)。HPV 16/18感染和IL-6及Mcl-1的表現也有顯著的相關性(IL-6：p=0.014；Mcl-1：p=0.004 )。另外，我們也觀察到HPV感染之肺腫瘤組織中IL-6與Mcl-1的表現有顯著的關聯性(p<0.0001)。
綜合以上結果，我們推論在肺腫瘤組織中，HPV16/18的感染可能透過IL-6及抗細胞凋亡蛋白Mcl-1的表現而參與肺腫瘤的形成。
Lung cancer is the leading cause of cancer death in nonsmoking Taiwanese women since 1982. The aetiology of lung cancer nonsmokers remains unknown. Environmental factors other than cigarette smoking were considered to link with lung cancer incidence of Taiwanese women. The association between human papillomavirus (HPV) 16/18 infection with nonsmoking Taiwanese female lung cancer has been reported. Previous report indicated that the anti-apoptotic effect of Mcl-1 is mediated by interleukin 6 (IL-6) expression in human cervical cancer tissues and cell lines that is closely associated with HPV infection. In this study, we attempted to reveal whether HPV infection was associated with the induction of Mcl-1 and IL-6 expression in lung tumor tissue in vivo. Immunohistochemistry data showed that 68% and 56% of IL-6 and Mcl-1 in 88 lung tumors had positively immunostainings, respectively. A significant association between IL-6 expression and tumor stage was observed (p = 0.043). The expression of IL-6 and Mcl-1 was significantly associated with HPV 16/18 infection (p = 0.014 and p = 0.004 respectively). We also observed that the expression of IL-6 was significantly correlated with Mcl-1 expression (p < 0.0001). These results strongly suggested that HPV infection may be involved in lung tumorigenesis through IL-6 and anti-apoptosis protein Mcl-1 concomitant expression.
