Hereditary non-polyposis colorectal cancer associated with disseminated superficial porokeratosis. Microsatellite instability in skin tumours
Hereditary non-polyposis colorectal cancer associated with disseminated superficial porokeratosis. Microsatellite instability in skin tumours
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DOI：
10.1046/j.1365-2133.2000.03789.x
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发表时间：
2000-10-01
影响因子：
10.3
通讯作者：
Takehara, K
中科院分区：
文献类型：
--
作者：
Takata, M;Shirasaki, F;Takehara, K
一位73岁男性，在脸部、躯干及四肢出现典型的播散性浅表汗孔角化症（DSP）及多发性脂溢性角化病，后来在唇部发展为角化棘皮瘤。他属于易患结肠癌、子宫癌和其他内部癌症的癌症易感家系，并且在59岁时有早期胃癌和降结肠晚期腺癌的个人病史，无腺瘤性息肉。聚合酶链反应扩增皮肤样本的7个独立的微卫星多态性显示微卫星不稳定性（MSI）在多个位点的6个脂溢性角化病和角化棘皮瘤，强烈建议潜在的缺陷，DNA错配修复。虽然没有发现两个错配修复基因hMSH2和hMLH1的种系突变，我们的病人被认为是遗传性非息肉病性结直肠癌（HNPCC）的基础上的家族史和皮肤肿瘤的微卫星分析的结果。这证实了在HNPCC家族筛查中检测MSI在普遍和容易获得的皮肤病变中的有用性，包括非皮脂腺非发育不良肿瘤，如脂溢性角化病。虽然DSP也可以作为一种常染色体显性遗传疾病，这种特殊的皮肤病似乎是散发在我们的病人，据我们所知，没有DSP或其他形式的汗孔角化症与HNPCC以前的报告。与脂溢性角化病和角化棘皮瘤相比，在两个DSP病变表皮样本中未观察到MSI。
A 73-year-old man presented with typical lesions of disseminated superficial porokeratosis (DSP) and multiple seborrhoeic keratoses on his face, trunk and extremities, and later developed a keratoacanthoma on his lip. He belonged to a cancer-prone pedigree susceptible to colonic, uterine and other internal cancers, and had a personal history of early gastric cancer and advanced adenocarcinoma of the descending colon without adenomatous polyps at age 59 years. Polymerase chain reaction amplification of skin samples for seven separate microsatellite polymorphisms revealed microsatellite instability (MSI) at multiple loci in five of six seborrhoeic keratoses and the keratoacanthoma, strongly suggesting underlying defects in DNA mismatch repair. Although no germline mutations in two mismatch repair genes hMSH2 and hMLH1 were found, our patient was recognized as having hereditary non-polyposis colorectal cancer (HNPCC) based on the family history and the findings of the microsatellite analysis of skin tumours. This confirmed the usefulness of detection of MSI in prevalent and readily accessible skin lesions, including non-sebaceous non-dysplastic tumours such as seborrhoeic keratosis in the screening of HNPCC families. Although DSP may also be inherited as an autosomal dominant condition, this particular skin disease appeared to be sporadic in our patient and, to our knowledge, no association of DSP or other forms of porokeratosis with HNPCC has previously been reported. In contrast to the seborrhoeic keratoses and keratoacanthoma, no MSI was observed in two samples from DSP lesional epidermis examined.