Amari Masakazu, Moriya Takuya, Ishida Takanori, Harada Yuko, Ohnuki Koji, Takeda Motohiro, Sasano Hironobu, Horii Akira, Ohuchi Noriaki
Division of Surgical Oncology, Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Jpn J Clin Oncol. 2003 Nov;33(11):556-62. doi: 10.1093/jjco/hyg109.
Ductal carcinoma in situ (DCIS) of the breast is known to possess characteristics of the pre-invasive stage of breast cancer and is the precursor to invasive ductal carcinoma (IDC). However, the natural history of the progression from DCIS to IDC remains unknown at the molecular level.
We investigated the loss of heterozygosities (LOHs) in tumors of seven patients with a history of breast biopsy. The seven specimens were diagnosed as DCIS on histopathological re-examination. These patients were diagnosed with ipsilateral breast cancer a few years after biopsy. We used thirteen selected microsatellite markers that were mapped to and/or very close to the tumor suppressor genes or regions with frequent LOHs in breast cancer. DNA isolated from microdissected formalin-fixed, paraffin-embedded tissues was subjected to a PCR-LOH analysis for these chromosome loci, and the pattern of LOHs was compared between the two asynchronous lesions for the seven cases.
In all patients except one, the LOHs were concordant at 91% as the informative chromosome loci in cases 1 to 6 were 56, and the concordance in LOH pattern between DCIS and IDC was detected at 50 loci. The LOHs had accumulated in accordance with the tumor progression from DCIS to IDC. The recurrent lesion occurred at or near the site of the primary biopsy and had similar or identical histopathologic features.
These recurrences observed were probably residual disease rather than true recurrences. Our results suggest the following: (i) genetic alternations accumulate during cancer progression from DCIS to IDC, (ii) DCIS is a lesion that has a high risk of developing invasive transformation and (iii) after approximately 5 years without treatment, DCIS may develop into IDC.
乳腺导管原位癌（DCIS）具有乳腺癌侵袭前阶段的特征，是浸润性导管癌（IDC）的前驱病变。然而，从DCIS进展到IDC的自然病程在分子水平上仍不清楚。
我们调查了7例有乳腺活检病史患者肿瘤中的杂合性缺失（LOH）情况。这7个标本经组织病理学重新检查诊断为DCIS。这些患者在活检后几年被诊断为同侧乳腺癌。我们使用了13个选定的微卫星标记，这些标记被定位到和/或非常接近肿瘤抑制基因或乳腺癌中频繁出现LOH的区域。从显微切割的福尔马林固定、石蜡包埋组织中分离的DNA对这些染色体位点进行PCR-LOH分析，并比较7例患者两个不同时期病变之间的LOH模式。
除1例患者外，所有患者中，作为信息性染色体位点，1至6例中91%的LOH是一致的，在50个位点检测到DCIS和IDC之间LOH模式的一致性。随着肿瘤从DCIS进展到IDC，LOH逐渐积累。复发病变发生在初次活检部位或其附近，具有相似或相同的组织病理学特征。
观察到的这些复发可能是残留疾病而非真正的复发。我们的结果表明：（i）在癌症从DCIS进展到IDC的过程中，基因改变会逐渐积累；（ii）DCIS是一种具有高侵袭性转化风险的病变；（iii）未经治疗约5年后，DCIS可能发展为IDC。
