小肠原发性腺癌的黏液表型和CD10表达
Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small intestine.
作者信息
Kumagai Reiko, Kohashi Kenichi, Takahashi Shunsuke, Yamamoto Hidetaka, Hirahashi Minako, Taguchi Kenichi, Nishiyama Kenichi, Oda Yoshinao
机构信息
Reiko Kumagai, Kenichi Kohashi, Shunsuke Takahashi, Hidetaka Yamamoto, Minako Hirahashi, Yoshinao Oda, Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
出版信息
World J Gastroenterol. 2015 Mar 7;21(9):2700-10. doi: 10.3748/wjg.v21.i9.2700.
AIM
To clarify the correlation with phenotypic expression, clinicopathological features, genetic alteration and microsatellite-instability status in small intestinal adenocarcinoma (SIA).
METHODS
The cases of 47 patients diagnosed with primary SIAs that were surgically resected at our institution in 1975-2005 were studied. We reviewed clinicopathological findings (age, gender, tumor size, gross appearance, histological morphologic type, invasion depth, lymphatic permeation, venous invasion, and lymph node metastasis), and the immunohistochemical expression of MUC5AC, MUC6, MUC2, CD10, and mismatch-repair (MMR) proteins (MLH1 and MSH2). We analyzed KRAS and BRAF gene mutations, and the microsatellite instability (MSI) status. The immunohistochemical staining of CD10, MUC2, MUC5AC and MUC6 was considered positive when distinct staining in > 5% of the adenocarcinoma cells was recorded. To evaluate of MMR protein expression, we used adjacent normal tissue including lymphoid follicles, inflammatory cells, and stromal cells as an internal positive control. Sections without nuclear staining in the tumor cells were considered to have lost the expression of the respective MMR protein.
RESULTS
There were 29 males and 18 females patients (mean age 59.9 years, range: 23-87 years). Tumors were located in the duodenum in 14 cases (30%), the jejunum in 21 cases (45%), and the ileum in 12 cases (25%). A phenotypic expression analysis revealed 20 MUC2-positive tumors (42.6%), 11 MUC5AC-positive (23.4%), 4 MUC6-positive (8.5%), and 7 CD10-positive (14.9%). The tumor sizes of the MUC2(+) tumors were significantly larger than those of the MUC2(-) tumors (mean, 5.7 ± 1.4 cm vs 4.7 ± 2.1 cm, P < 0.05). All three tumors with adenomatous component were positive for MUC2 (P < 0.05). Polypoid appearance was seen significantly more frequently in the CD10(+) group than in the CD10(-) group (P < 0.05). The tumor size was significantly larger in the CD10 (+) group than in the CD10(-) group (mean, 5.9 ± 1.4 cm vs 5.0 ± 2.1 cm, P < 0.05). Of 34 SIAs with successfully obtained MSI data, 4 were MSI-high. Of the 4 SIAs positive for both MUC5AC and MUC2, 3 showed MSI-H (75%) and 3 were mucinous adenocarcinoma (75%). KRAS mutations were detected in 4 SIAs. SIAs had KRAS mutation expressed only MUC2, but were negative for MUC5AC, MUC6 and CD10.
CONCLUSION
These findings suggest that the phenotypic expression of SIAs is correlated with their biological behavior, genetic alteration, and MSI status.
目的
阐明小肠腺癌（SIA）的表型表达、临床病理特征、基因改变及微卫星不稳定性状态之间的相关性。
方法
对1975年至2005年在本机构接受手术切除的47例原发性SIA患者的病例进行研究。我们回顾了临床病理结果（年龄、性别、肿瘤大小、大体外观、组织形态学类型、浸润深度、淋巴浸润、静脉浸润及淋巴结转移），以及MUC5AC、MUC6、MUC2、CD10和错配修复（MMR）蛋白（MLH1和MSH2）的免疫组化表达。我们分析了KRAS和BRAF基因突变以及微卫星不稳定性（MSI）状态。当在>5%的腺癌细胞中记录到明显染色时，CD10、MUC2、MUC5AC和MUC6的免疫组化染色被视为阳性。为评估MMR蛋白表达，我们使用包括淋巴滤泡、炎性细胞和基质细胞的相邻正常组织作为内部阳性对照。肿瘤细胞中无核染色的切片被认为相应MMR蛋白表达缺失。
结果
患者中男性29例，女性18例（平均年龄59.9岁，范围：23 - 87岁）。肿瘤位于十二指肠14例（30%），空肠21例（45%），回肠12例（25%）。表型表达分析显示，20例肿瘤MUC2阳性（42.6%），11例MUC5AC阳性（23.4%），4例MUC6阳性（8.5%），7例CD10阳性（14.9%）。MUC2（+）肿瘤的大小显著大于MUC2（ - ）肿瘤（平均5.7±1.4 cm对4.7±2.1 cm，P<0.05）。所有三个具有腺瘤成分的肿瘤MUC2均为阳性（P<0.05）。CD10（+）组中息肉样外观的出现频率显著高于CD10（ - ）组（P<0.05）。CD10（+）组的肿瘤大小显著大于CD10（ - ）组（平均5.9±1.4 cm对5.0±2.1 cm，P<0.05）。在成功获得MSI数据的34例SIA中，4例为MSI高。在4例MUC5AC和MUC2均阳性的SIA中，3例显示MSI-H（75%），3例为黏液腺癌（75%）。在4例SIA中检测到KRAS突变。发生KRAS突变的SIA仅表达MUC2，但MUC5AC、MUC6和CD10均为阴性。
结论
这些发现表明SIA的表型表达与其生物学行为、基因改变及MSI状态相关。
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