Study of cell proliferation and oncogenesis in pulmonary fibrosis. Kyushu University Research Institute for Diseases of the Chest

据报道，7%至30%的特发性间质性肺炎（IIP）患者与肺癌相关。然而，8%的肺癌患者与IIP相关，35%的肺癌患者存在肺间质改变。这些事实表明，肺纤维化作为肺癌发生的背景具有重要作用。本文对20例伴有肺间质改变的肺癌患者的肺组织进行了细胞增殖和癌变机制的研究，70%的肺癌组织中p53蛋白表达阳性。纤维化区肺泡上皮和细支气管上皮细胞阳性率为45%。在纤维化区，染色强度较低，染色模式分散。PCNA在癌区的阳性率为90%，在纤维化区的阳性率为60%，阳性区呈不均匀分布于支气管上皮周围。癌组织中未见Fas表达。纤维化区TUNEL染色阳性率为50%。结果表明，肺纤维化组织中细胞增殖与细胞损伤（或凋亡）同时发生，且p53与PCNA呈阳性表达。提示肺纤维化组织中存在DNA损伤和修复，导致肺癌的发生。为了明确肺纤维化中p53表达是否代表p53。突变作为癌前病变或表达野生型p53以保持DNA稳定性，这些区域的p53基因分析正在进行中。

It is reported that 7% to 30% of patients with idiopathic interstitial pneumonia (IIP) are associated with lung cancer. Inversely, 8% of patients with lung cancer are associated with IIP,and 35%of patients with lung cancer have pulmonary interstitial changes. These facts indicate that pulmonary fibrosis has an important role as a background of lung carcinogenesis. We haveinvestigated the mechanisms of cell proliferation and carcinogenesis for the lung tissue from 20 patients with lung cancer associated with pulmonary interstitial changes.In cancer tissue immunohistochemical expression of p53 was observed in 70% of the cases. while, in alveolar and bronchiolar epithelium of fibrosis area, it was observed in 45% of the cases. In fibrosis area, the staining intensity was lower, and the staining pattern was scattered. Positive ratio of PCNA was 90% in cancer area, and 60% in fibrosis area in which positive area was distributed unequally around bronchial epithelium. No expression of Fas was seen in cancer area. Positive ratio of TUNEL stain in fibrotic area was 50%. In the cases multiple area was anlyzed by step section for p53 expression, PCNA expression and TUNEL stain, co-expression of p53 and PCNA, and simultaneous DNA damage were foca11y observed.These results indicate that both cell proliferatioh and cell damage (or apoptosis) occur simultaneously in tissue exhibiting pulmonary fibrosis. Thus, it is suggested that DNA damage and repair are seen in the tissue with pulmonary flbrosis, leading to luhg carcinogenesis. In order to clarify whether p53 expression in pulmonary fibrosis represents p53. mutation as precancerous lesion or expression of wild type p53 to preserve DNA stability, p53 gene analysis ln these area are now ongoing.