Ramachandran S, Fryer A A, Strange R C
Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, North Staffordshire Hospital, Keele University, Staffordshire, England, UK.
Med Pediatr Oncol. 2001 May;36(5):559-63. doi: 10.1002/mpo.1130.
Basal cell carcinoma (BCC) patients demonstrate considerable phenotypic diversity. The basis of this heterogeneity is poorly understood. We have shown that presentational phenotypes are associated with BCC numbers. Thus, patients with a cluster of new BCC at any presentation comprise a subgroup, termed MPP, that is at increased risk of developing numerous lesions. Patients with more than one cluster (multiple cluster MPP) are at particular risk.
We determined in a cohort of BCC cases, whether: (i) tumor accrual was altered after clustering; and (ii) multiple cluster MPP is associated with characteristics linked with sensitivity to UV or, GSTT1, GSTM1, GSTM3, GSTP1, MC1R, CYP2D6, TNF-alpha, and VDR genotypes previously associated with BCC presentational phenotypes.
(i) After clustering BCC accrual increased; and (ii) exposure to UV in single and multiple cluster MPP cases were similar. In multiple cluster cases, mean age at first presentation with a single tumor occurred earlier and, the frequencies of CYP2D6 EM (94.4%) and GSTT1 null (41.2%) were significantly greater (P = 0.028 and P = 0.004) than in single cluster cases (67.1 and 14.3%). The odds ratios for these associations with the multiple cluster MPP were large; 15.5 and 7.39, respectively.
The finding of clusters of new, primary BCC is a critical event that is followed by markedly increased accrual of further tumors. Clustering occurs at a relatively late age and may be associated with a failure in immune surveillance. We propose the MPP is not the consequence of excessive UV exposure but reflects the presence of a distinct BCC subgroup defined by a combination of risk genes.
基底细胞癌（BCC）患者表现出相当大的表型多样性。这种异质性的基础尚不清楚。我们已经表明，呈现的表型与BCC数量有关。因此，在任何一次就诊时出现一群新发BCC的患者构成一个亚组，称为多原发性皮损（MPP），该亚组发生大量皮损的风险增加。有多个皮损群（多群MPP）的患者风险尤其高。
我们在一组BCC病例中确定：（i）皮损聚集后肿瘤累积是否改变；以及（ii）多群MPP是否与先前与BCC呈现表型相关的紫外线敏感性或谷胱甘肽S-转移酶T1（GSTT1）、谷胱甘肽S-转移酶M1（GSTM1）、谷胱甘肽S-转移酶M3（GSTM3）、谷胱甘肽S-转移酶P1（GSTP1）、黑素皮质素受体1（MC1R）、细胞色素P450 2D6（CYP2D6）、肿瘤坏死因子-α（TNF-α）和维生素D受体（VDR）基因型相关的特征有关。
（i）皮损聚集后BCC累积增加；（ii）单群和多群MPP病例的紫外线暴露情况相似。在多群病例中，首次出现单个肿瘤时的平均年龄较早，细胞色素P450 2D6快代谢型（EM）（94.4%）和谷胱甘肽S-转移酶T1缺失型（41.2%）的频率显著高于单群病例（67.1%和14.3%）（P = 0.028和P = 0.004）。这些与多群MPP的关联的优势比很大；分别为15.5和7.39。
新发原发性BCC皮损群的发现是一个关键事件，随后进一步肿瘤的累积明显增加。皮损聚集发生在相对较晚的年龄，可能与免疫监视失败有关。我们提出，MPP不是过度紫外线暴露的结果，而是反映了由一组风险基因定义的一个独特的BCC亚组的存在。
