Tsutsumida Hideaki, Nomoto Mitsuharu, Goto Masamichi, Kitajima Shinichi, Kubota Ichiro, Hirotsu Yasunobu, Wakimoto Joeji, Hollingsworth Michael A, Yonezawa Suguru
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Mod Pathol. 2007 Jun;20(6):638-47. doi: 10.1038/modpathol.3800780. Epub 2007 Apr 13.
A micropapillary pattern is defined as papillary tufts without a fibrovascular core and is known to be a factor that indicates a poor prognosis in numerous cancers. However, their role in lung adenocarcinoma has not been investigated widely. In 185 cases of small-size lung adenocarcinoma (< or =3 cm), cases with a micropapillary pattern ratio of more than 1% (analyzed by NIH image) were defined as micropapillary pattern positive. Correlations between the micropapillary pattern and clinicopathological factors were investigated and immunohistochemical expression of mucin and various antigens was examined in regions with and without micropapillary patterns. Micropapillary pattern-positive tumors (micropapillary pattern ratio > or =1%) were observed in 11.4% of cases (21/185) and the micropapillary pattern ratio correlated with TNM stage (P=0.0002), lymphatic invasion (P=0.0002) and lymph node metastasis (P=0.03). Disease-free interval (P<0.0002) and survival (P=0.027) were significantly shorter for micropapillary pattern-positive patients, and micropapillary pattern-positive stage IA cases also had a significantly shorter disease-free interval (P<0.0001). MUC1 was expressed strongly across the surface of the micropapillary structure, whereas MUC4 tended to show lower expression in the micropapillary pattern. It was noteworthy that the disease-free interval in patients with high surfactant apoprotein A expression was significantly better than in patients with low surfactant apoprotein A expression (P=0.03), and no recurrence or death occurred in patients with high surfactant apoprotein A expression. Our results show that the micropapillary pattern ratio correlates with lymphatic invasion and lymph node metastasis, and that a high micropapillary pattern ratio leads to a poor prognosis. High MUC1 expression on the surface is an important characteristic of a micropapillary pattern, and reduced surfactant apoprotein A expression in the micropapillary pattern may be an excellent indicator for poor prognosis in small-size lung adenocarcinoma.
微乳头模式被定义为没有纤维血管核心的乳头簇，并且已知是多种癌症中提示预后不良的一个因素。然而，它们在肺腺癌中的作用尚未得到广泛研究。在185例小尺寸肺腺癌（≤3 cm）中，微乳头模式比例超过1%（通过美国国立卫生研究院图像分析）的病例被定义为微乳头模式阳性。研究了微乳头模式与临床病理因素之间的相关性，并在有和无微乳头模式的区域检查了黏蛋白和各种抗原的免疫组化表达。11.4%的病例（21/185）观察到微乳头模式阳性肿瘤（微乳头模式比例≥1%），微乳头模式比例与TNM分期（P = 0.0002）、淋巴侵犯（P = 0.0002）和淋巴结转移（P = 0.03）相关。微乳头模式阳性患者的无病生存期（P < 0.0002）和生存期（P = 0.027）显著缩短，微乳头模式阳性的IA期病例无病生存期也显著缩短（P < 0.0001）。MUC1在微乳头结构表面强烈表达，而MUC4在微乳头模式中倾向于显示较低表达。值得注意的是，表面活性物质载脂蛋白A高表达患者的无病生存期明显优于表面活性物质载脂蛋白A低表达患者（P = 0.03），表面活性物质载脂蛋白A高表达患者未发生复发或死亡。我们的结果表明，微乳头模式比例与淋巴侵犯和淋巴结转移相关，高微乳头模式比例导致预后不良。表面高表达MUC1是微乳头模式的一个重要特征，微乳头模式中表面活性物质载脂蛋白A表达降低可能是小尺寸肺腺癌预后不良的一个极佳指标。
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