Takashima Yasutoshi, Murakami Teppei, Inoue Takao, Hagiyama Man, Yoneshige Azusa, Nishimura Syunji, Akagi Masao, Ito Akihiko
1 Department of Pathology, Faculty of Medicine, Kindai University, Osaka, Japan.
2 Department of Orthopaedic Surgery, Faculty of Medicine, Kindai University, Osaka, Japan.
Tumour Biol. 2017 Jun;39(6):1010428317704365. doi: 10.1177/1010428317704365.
Epithelial carcinomas occasionally have sarcomatous components that consist primarily of spindle and cuboidal cells, which often resemble osteoblasts. Sarcomatoid carcinomas consist of similar cells. Recent studies have characterized these phenomena as a manifestation of epithelial-mesenchymal transition in carcinoma cells, but the mesenchymal phenotypes that manifest in sarcomatous cells of epithelial carcinomas are not well understood. Here, we examined the expression profiles of four osteoblastic differentiation biomarkers in the sarcomatous components of multiple carcinoma types, including five renal clear cell, four breast invasive ductal, two esophageal, one maxillary squamous cell, three larynx, three lung, one liver, and one skin sarcomatoid carcinoma. Expression was analyzed by immunohistochemistry using antibodies against cell adhesion molecule 1, a member of the IgCAM superfamily, osterix transcription factor (Osterix), cluster of differentiation 151, a transmembrane 4 superfamily member, and alkaline phosphatase. Immunostaining intensity was rated in scale 0 (negative), 0.5 (weak), and 1 (strong) for each marker, and the four scale values were summed to calculate osteoblastic scores. In all, 10 cases had a osteoblastic score ≥3, and all of these 10 cases were cell adhesion molecule 1- and Osterix-positive. Eight and five of the nine samples with a osteoblastic score <3 were negative for cell adhesion molecule 1 ( p < 0.0001) and Osterix ( p = 0.006), respectively. The other markers showed no statistical significance. These results indicate that osteoblastic differentiation can occur in carcinoma cells and that cell adhesion molecule 1 could be a useful marker for identifying this phenomenon in carcinoma tissues.
上皮癌偶尔会有肉瘤样成分，主要由梭形细胞和立方形细胞组成，这些细胞常类似于成骨细胞。肉瘤样癌也由类似的细胞组成。最近的研究将这些现象表征为癌细胞上皮-间质转化的一种表现，但上皮癌肉瘤样细胞中表现出的间质表型尚未得到充分了解。在此，我们检测了多种癌类型的肉瘤样成分中四种成骨细胞分化生物标志物的表达谱，包括五例肾透明细胞癌、四例乳腺浸润性导管癌、两例食管癌、一例上颌鳞状细胞癌、三例喉癌、三例肺癌、一例肝癌和一例皮肤肉瘤样癌。使用针对免疫球蛋白细胞粘附分子超家族成员细胞粘附分子1、osterix转录因子（Osterix）、跨膜4超家族成员分化簇151和碱性磷酸酶的抗体，通过免疫组织化学分析表达情况。对每个标志物的免疫染色强度按0（阴性）、0.5（弱阳性）和1（强阳性）进行评分，并将四个评分值相加计算成骨细胞评分。总共10例成骨细胞评分≥3，这10例均为细胞粘附分子1和Osterix阳性。成骨细胞评分<3的九个样本中，分别有八个和五个样本细胞粘附分子1（p<0.0001）和Osterix（p = 0.006）呈阴性。其他标志物无统计学意义。这些结果表明癌细胞可发生成骨细胞分化，细胞粘附分子1可能是识别癌组织中这种现象的有用标志物。
