肝癌のclonalityの研究は、HBV関連肝細胞癌はHBV遺伝子の組み込みで評価できるがH BV感染を認めない場合はいい方法がないとのことでした。順天堂第一病理の藤井先生 のテクノロジーを用いると、ホルマリン固定標本で、LOH (loss of heterozygosity) を調べることで判定できるようです。彼は乳癌や膵癌でこの研究を行っていますが、 肝細胞癌にも応用可能な方法であり、多中心性肝発癌と肝内転移巣を鑑別する画期的 方法になると予想されます。(柴田）

参考文献です：

Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas.

Kuniyasu H; Yasui W; Yokozaki H; Akagi M; Akama Y; Kitahara K; Fujii K; Tahara E

Department of Pathology, Hiroshima University School of Medicine, Japan.

Int J Cancer, 1994 Dec 1, 59:5, 597-600

Loss of heterozygosity (LOH) on the long arm of chromosome 7 was examined using 5 polymorphic marker probes on 98 gastric carcinomas to elucidate a novel locus for development and progression of the tumors. Twenty-six (32%) of 82 informative cases showed LOH on 7q on at least one locus of 5 loci. Among 5 loci, LOH at D7S95 locus was most frequent, the incidence being 53% in well-differentiated gastric carcinomas and 33% in poorly differentiated and scirrhous gastric carcinomas respectively. At 3 loci, c-met, D7S63 and D7S22, the incidence of LOH was about 30% and 10% in well-differentiated and poorly differentiated gastric carcinoma cases respectively. In contrast, LOH at D7S64 was not detected in any gastric-carcinoma cases. Deletion mapping of 7q revealed that D7S95 locus was the essential region of LOH. Eight (62%) of 13 cases with LOH at D7S95 locus belonged to the most advanced stage grouping. Furthermore, 6 (75%) of 8 cases with abdominal dissemination showed LOH at D7S95. Therefore, cases with LOH at D7S95 showed significantly worse prognosis than the cases without the LOH in the stage-III and stage-IV groups. These findings overall suggest that D7S95 locus on 7q may contain a candidate suppressor gene for the progression of gastric carcinoma.

Genetic progression, histological grade, and allelic loss in ductal carcinoma in situ of the breast.

Fujii H; Szumel R; Marsh C; Zhou W; Gabrielson E

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA.

Cancer Res, 1996 Nov 15, 56:22, 5260-5

To investigate the relationships of specific allelic losses to progression and histological grade of ductal carcinoma in situ (DCIS) of the breast, we studied PCR-amplified microsatellite markers on ten chromosomal arms in 41 cases of DCIS without synchronous invasive cancer. For all chromosomal arms combined, the number of allelic losses was significantly greater in lesions of intermediate or high nuclear grade (5.6 chromosomal arms/case) than in lesions of low nuclear grade (1.2 chromosomal arms/case). Allelic losses of 16q and 17p were commonly found in low nuclear grade DCIS (38 and 34%, respectively) as well as in intermediate and high nuclear grade DCIS (58 and 95%, respectively). Allelic losses of other chromosomal arms examined (1p, 1q, 6q, 9p, 11p, 11q, 13q, and 17q) were uncommonly seen in low-grade DCIS, but were seen at frequencies of greater than 40% in intermediate- and high-grade DCIS. In 10 of the cases (24%), we identified patterns of allelic loss heterogeneity suggestive of intralesional progression, findings that were possible because multiple tumor foci from each lesion were individually microdissected and studied. For these tumors with allelic loss heterogeneity, we reasoned that chromosomal losses common to all tumor foci most likely preceded the chromosomal losses observed only in tumor foci of a more advanced genetic stage. In 9 of these 10 cases, all tumor foci lost 16q, and in 8 of the 10 cases, all tumor foci lost 17p. Together, these observations indicate that chromosomal losses of 16q and 17p occur early in DCIS progression and are common even in low-grade DCIS. Tumors of intermediate and high nuclear grade usually have allelic losses of significantly more chromosomal arms, often including 1p, 1q, 6q, 9p, 11p, 11q, 13q, and 17q. Allelic loss of these chromosomal arms may occur later in DCIS progression.