Molecular pathological analyses of single tumor gland using crypt isolation method in 25 endometrial carcinoma patients

25例子宫内膜癌患者隐窝分离法对单个肿瘤腺体的分子病理分析

• 批准号: 20791158
• 负责人: NAGASAWA Takayuki
• 金额: $ 2.33万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20791158/
• 关键词: 子宮体癌; 腺管分離; 遺伝子解析

We analyzed molecular abnormarityies of single tumor glands using crypt isolation method in 25 endometrial endometrioid adenocarcinoma patients. In addition, we investigated the relation between the form of molecular abnormalities among single tumor gland and the disease prognosis. The frequency of LOH in the pooled gland sample obtained using crypt isolation was higher in many loci than that in the sample obtained using the conventional method, in which crypt isolation was not used. This suggests that by analyzing a pure sample of only tumor glands obtained using crypt isolation, gene abnormalities that cannot be detected in samples obtained by the conventional method can be detected and that the analysis sensitivity is improved. With the exception of local recurrence, progression of cancer during therapy or recurrence after therapy was observed in 4 cases. From the view point of genetic abnormality, the 3 cases had LOH in a plurality of regions and heterogeneity among single tumor glands. Among the other case, although LOH was not found in the pooled gland sample, it was only found in some single tumor gland samples. All 4 cases had LOH in the 5 q loci at least in a single tumor gland. This suggests the possibility that although LOH in the 5 q has a minor role in endometrial carcinogenesis, it is a poor prognostic factor. Heterogeneity of gene abnormality between single tumor glands was confirmed in 16 (64%) of the 25 cases, indicating that endometrial carcinoma consists of various single tumor glands with different molecular abnormalities. In addition, it was suggested that the form of gene abnormalities in individual tumor glands is related to sensitivity and resistance to chemotherapy.

我们在25个子宫内膜子宫内膜类腺癌患者中使用隐窝分离方法分析了单个肿瘤腺的分子异常。此外，我们研究了单个肿瘤腺之间分子异常形式与疾病预后之间的关系。在许多基因座中获得的合并腺样品中LOH的频率高于使用常规方法获得的样品中的LOH，在该方法中，未使用隐窝分离。这表明，通过分析仅使用隐窝分离获得的肿瘤腺的纯样品，可以检测到在通过常规方法获得的样品中无法检测到的基因异常，并提高了分析敏感性。除局部复发外，在4例中观察到治疗期间癌症或治疗后癌症的进展。从遗传异常的角度来看，这3例在多个区域和单个肿瘤腺之间的异质性中有LOH。在另一个情况下，尽管在合并的腺样品中未发现LOH，但仅在某些单个肿瘤腺样品中发现。所有4例在5 Q基因座中至少在单个肿瘤腺中都有LOH。这表明，尽管5 Q中的LOH在子宫内膜癌变中具有较小的作用，但它是一个差的预后因素。在25例25例中，有16例（64％）证实了单个肿瘤腺之间基因异常的异质性，这表明子宫内膜癌由各种分子异常的各种单肿瘤组成。此外，有人提出，个体肿瘤腺体中基因异常的形式与对化学疗法的敏感性和抗性有关。

项目成果

子宮内膜癌における腺管分離法を用いた単一癌腺管の分子病理学的解析永沢崇幸

子宫内膜癌单管癌导管分离的分子病理学分析 Takayuki Nagasawa

• 发表时间: 2008
• 作者: 菅井有;庄子忠宏;杉山徹
• 通讯作者: 杉山徹