Furuya T, Uchiyama T, Murakami T, Adachi A, Kawauchi S, Oga A, Hirano T, Sasaki K
Department of Pathology, Yamaguchi University School of Medicine, Ube, Japan.
Clin Cancer Res. 2000 Jul;6(7):2815-20.
The purpose of this study was to elucidate the relationship between intratumoral regional heterogeneity in DNA ploidy and chromosomal instability (CIN) in primary gastric adenocarcinomas. In 45 sporadic gastric adenocarcinomas, we measured DNA ploidy and numerical aberrations for chromosomes 7, 11, 17, and 18 by laser scanning cytometry and fluorescence in situ hybridization, respectively, in small tissue specimens taken from 2 to 6 (on the average 4) different portions of the same tumor. A total of 231 specimens including 45 normal control specimens were examined. All 98 tumor specimens with DNA aneuploidy (DNA index > or = 1.2) showed large intercellular variations in chromosome copy number, indicating CIN. In contrast, 85 tumor specimens with (near) diploidy (1.0 < or = DNA index < 1.2) exhibited much small intercellular variations in chromosome copy number as compared with aneuploid specimens (P < 0.0001). The relationship between DNA ploidy and intercellular variation in chromosome copy number was true for tumors consisting of a mixture of (near) diploid and aneuploid subpopulations. These data indicate that DNA aneuploidy is associated with CIN but that (near) diploidy is not. Intratumoral regional DNA ploidy heterogeneity was conspicuous in 33 (92%) of 36 tumors with regions of DNA aneuploidy, and all aneuploid specimens showed great intercellular variation in chromosome copy number. Diploid regions were predominant in early stage cancers (intramucosal and submucosal cancers), and five of eight early cancers contained only diploid population. In contrast, all tumors without (near) diploid regions were advanced cancers. These observations suggest that CIN is a necessary prerequisite for developing intratumoral DNA ploidy heterogeneity with DNA aneuploidy.
本研究的目的是阐明原发性胃腺癌中DNA倍体的肿瘤内区域异质性与染色体不稳定性（CIN）之间的关系。在45例散发型胃腺癌中，我们分别通过激光扫描细胞术和荧光原位杂交，对取自同一肿瘤2至6个（平均4个）不同部位的小组织标本进行了DNA倍体以及7号、11号、17号和18号染色体的数目畸变检测。总共检测了包括45个正常对照标本在内的231个标本。所有98例DNA非整倍体（DNA指数≥1.2）的肿瘤标本均显示出染色体拷贝数的巨大细胞间变异，表明存在CIN。相比之下，85例（近）二倍体（1.0≤DNA指数＜1.2）的肿瘤标本与非整倍体标本相比，染色体拷贝数的细胞间变异要小得多（P＜0.0001）。对于由（近）二倍体和非整倍体亚群混合组成的肿瘤，DNA倍体与染色体拷贝数的细胞间变异之间的关系也是成立的。这些数据表明，DNA非整倍体与CIN相关，而（近）二倍体则不然。在36例存在DNA非整倍体区域的肿瘤中，33例（92%）肿瘤内区域DNA倍体异质性明显，所有非整倍体标本均显示出染色体拷贝数的巨大细胞间变异。二倍体区域在早期癌症（黏膜内癌和黏膜下癌）中占主导地位，8例早期癌症中有5例仅包含二倍体细胞群。相反，所有没有（近）二倍体区域的肿瘤均为进展期癌症。这些观察结果表明，CIN是产生具有DNA非整倍体的肿瘤内DNA倍体异质性的必要前提条件。
