Gene Abberation Analysis in Precancerous Lesion of the Lung Adenocarcinoma by Laser Microdissection System

激光显微切割系统对肺腺癌癌前病变的基因畸变分析

• 批准号: 10670165
• 负责人: HASHIMOTO Shuichi
• 金额: $ 1.92万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670165/
• 关键词: Lung Cancer; Atypical Adenomatous Hyperplasia (AAH); SP-A; proSP-C; CC10; p53; Ki-67 (MIB-1); Microdissection; レーザーマイクロディセクション

Totally 65 AAH lesions(low/high grade atypia =45/20) were obtained from 13 of 21 (62%) cases surgically resected for peripheral type lung adenocarcinomas. The mean size of the AAH lesions was 1.7 mm in low grade AAH and 3.7 mm in high grade AAH (p<0.0001). All of the 4 AAH lesions over 5 mm in diameter showed high grade atypia. The means of the nuclear size and area were 7.22μm and 28.23μmィイD12ィエD1 in low grade AAH and 8.20μm and 36.01μmィイD12ィエD1 in high grade AAH(p=0.002 and p<0.0001, respectively). Nuclear size and nuclear area were also positively correlated with the AAH size(p<0.0001, in each). P53 and MIB-1 indexes also trend to increase from low grade AAH, to high grade AAH and to primary adenocarcinoma(p<0.0001, in each). These histopathological findings suggest that there is already a step-up in the atypia, lesion size, p53 and MIB-1 indexes from low grade to high grade AAH, and support the possibility that human AAH with high grade atypia is a precancerous lesion of peripheral lung adenocarcinoma. In addition, atypical cells in both low and high grade AAH lesions were immunohistochemically positive to SP-A and proSP-C(100%, in each), but negative to CC10(0%, in each), which indicates that the atypical cells of AAH lesions share the phenotypical characteristics of type II pneumocytes, and thus offers further support the hypothesis that AAH lesions largely may imply the proliferative lesion of type II pneumocytes of their derivative cells. In the gene abberation analysis, p53 gene abberation in exon 5 was noted in 4 of the 12 primary adenocarcinoma cases in which both AAH and primary adenocarcinoma could be aplied for p53 gene abberation analysis. One low grade AAH involved in one of the previous 4 casese revealed a same band shift with that of the primary adenocarcinoma.

21例周围型肺腺癌手术切除病例中，13例（62%）共获得65个AAH病灶（低度/高度异型性=45/20）。低级别 AAH 中 AAH 病变的平均大小为 1.7 mm，高级别 AAH 中 AAH 病变的平均大小为 3.7 mm (p<0.0001)。 4个直径超过5毫米的AAH病灶均表现出高度异型性。低级别AAH中核大小和面积的平均值为7.22μm和28.23μmィイD12ィエD1，高级别AAH中为8.20μm和36.01μmィイD12ィエD1（分别为p=0.002和p​​<0.0001）。核大小和核面积也与 AAH 大小呈正相关（p<0.0001）。 P53 和 MIB-1 指数也有从低级别 AAH 到高级别 AAH 和原发性腺癌升高的趋势（均 <0.0001）。这些组织病理学结果表明，从低级别到高级别 AAH，异型性、病灶大小、p53 和 MIB-1 指数已经有所提高，并支持具有高级别异型性的人 AAH 是周围型肺腺癌的癌前病变的可能性。此外，低度和高度AAH病变中的非典型细胞免疫组化SP-A和proSP-C均呈阳性（各100%），而CC10阴性（各0%），这表明AAH病变的非典型细胞具有II型肺细胞的表型特征，从而进一步支持了AAH病变很大程度上可能意味着增殖的假设。 II型肺细胞及其衍生细胞的损伤。在基因畸变分析中，在12例原发性腺癌病例中，有4例发现第5外显子的p53基因畸变，其中AAH和原发性腺癌均可用于p53基因畸变分析。前 4 例病例中的 1 例涉及低级别 AAH，显示与原发性腺癌相同的条带偏移。