杂合性缺失分析显示，食管癌肉瘤存在单克隆进化，伴有频繁的基因进展和分化。

Loss of heterozygosity analysis shows monoclonal evolution with frequent genetic progression and divergence in esophageal carcinosarcoma.

作者信息

Matsumoto Toshiharu, Fujii Hiroaki, Arakawa Atsushi, Yamasaki Shigetaka, Sonoue Hiroshi, Hattori Kimiaki, Kajiyama Yoshiaki, Hirose Sachiko, Tsurumaru Masahiko

机构信息

First Department of Pathology, Juntendo University, School of Medicine, Tokyo, Japan.

出版信息

Hum Pathol. 2004 Mar;35(3):322-7. doi: 10.1016/j.humpath.2003.02.001.

DOI:10.1016/j.humpath.2003.02.001

PMID:15017588

Abstract

Carcinosarcoma (spindle cell carcinoma) of the esophagus is a rare neoplasm that shows squamous cell carcinoma (SCC) with a variable component of spindle cell sarcoma. Clinical and pathologic features of this neoplasm have been well documented, but the histogenesis has long been a matter of speculation and dispute. In an attempt to clarify the clonality and genetic relationships in the evolution of this neoplasm, we microdissected a total of 36 carcinomatous and sarcomatous foci from six esophageal carcinosarcoma (CS) and analyzed the allelic status with 25 microsatellite markers on chromosomal arms 3p, 5q, 6q, 8p, 9p, 11q, 13q, 17p, and 18q. In all cases, we found multiple and homogenous allelic losses in both the carcinomatous and sarcomatous components, strongly supporting the concept of monoclonal origin for this neoplasm. Homogeneous allelic losses were detected most frequently on 17p (5 cases), a chromosomal arm that included the p53 locus, followed by 3p, 11q, and 13q (3 cases); 9p (2 cases); and 8p and 18q (1 case). Moreover, five of the six cases showed additional or divergent allelic losses at more than one chromosomal locus at some of the microdissected foci, indicating genetic progression (2 cases) or genetic progression and divergence (3 cases). In four cases, the genetic changes indicated that an original clone of a pure SCC apparently acquired carcinosarcomatous or sarcomatous phenotype by successive genetic changes. On the other hand, we saw no evidence for tumors in which a sarcoma appeared to give rise to a carcinosarcomatous or carcinomatous subclone in the examined cases. In conclusion, our data support the concept that esophageal CS is derived from a single clone originating from a SCC. Furthermore, we showed genetic heterogeneity to accompany the phenotypic divergence, with patterns of genetic alterations that are consistent with both progression and divergence within individual tumors.

摘要

食管癌肉瘤（梭形细胞癌）是一种罕见的肿瘤，表现为鳞状细胞癌（SCC）伴有不同比例的梭形细胞肉瘤成分。该肿瘤的临床和病理特征已有充分记录，但组织发生长期以来一直是推测和争议的问题。为了阐明该肿瘤演变过程中的克隆性和遗传关系，我们从6例食管肉瘤样癌（CS）中总共显微切割了36个癌灶和肉瘤灶，并用位于染色体臂3p、5q、6q、8p、9p、11q、13q、17p和18q上的25个微卫星标记分析了等位基因状态。在所有病例中，我们在癌灶和肉瘤灶中均发现了多个且一致的等位基因缺失，有力地支持了该肿瘤单克隆起源的概念。在17p（5例）上最常检测到一致的等位基因缺失，该染色体臂包含p53基因座，其次是3p、11q和13q（3例）；9p（2例）；8p和18q（1例）。此外，6例中的5例在一些显微切割灶的多个染色体位点显示出额外的或不同的等位基因缺失，表明存在基因进展（2例）或基因进展和分化（3例）。在4例中，基因变化表明一个纯SCC的原始克隆显然通过连续的基因变化获得了癌肉瘤或肉瘤样表型。另一方面，在所检查的病例中，我们没有发现肉瘤似乎产生癌肉瘤或癌性子克隆的肿瘤证据。总之，我们的数据支持食管CS起源于源自SCC的单个克隆的概念。此外，我们显示遗传异质性伴随着表型分化，其基因改变模式与单个肿瘤内的进展和分化均一致。