Qunn Lei, Takemura Tamiko, Ikushima Soichiro, Ando Tsunehiro, Yanagawa Takashi, Akiyama Osamu, Oritsu Masaru, Tanaka Noboru, Kuroki Toshio
Department of Pathology, Japanese Red Cross Medical Center, 4-1-22, Hiroo, Shibuya-ku, Tokyo 150-8935, Japan.
Virchows Arch. 2002 Sep;441(3):271-8. doi: 10.1007/s00428-002-0618-9. Epub 2002 Mar 21.
Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.
对1973年至1996年东京日本红十字会医疗中心连续2856例尸检病例中的72例特发性肺纤维化（IPF）进行了检查。72例IPF患者中有31例（43%）发生了原发性肺癌，显著高于无IPF患者（8.1%）和非IPF慢性肺病患者（11.9%）的发病率。IPF病例蜂窝状病变中的增生性上皮灶在下叶比上叶更明显，无论有无肺癌，且在伴有肺癌的IPF下叶比无癌的更明显。IPF病例下叶增生性上皮灶的长度比与胶原血管病相关的间质性肺炎中的更长。IPF病例增生性上皮灶的增殖细胞核抗原（PCNA）标记指数高于与胶原血管病相关的间质性肺炎病例。吸烟者和非吸烟者IPF的PCNA标记指数几乎相同。在IPF蜂窝状病变的增生性上皮灶中观察到p53的过表达。对12例IPF病例石蜡切片中的增生性上皮灶进行DNA倍体分析，8例显示非整倍体模式。这些结果强烈表明，IPF的蜂窝状病变中发生了加速的细胞增殖，并且除吸烟影响外，再生上皮对致癌剂变得易感。
