Nuclear PTEN expression and clinicopathologic features in a population-based series of primary cutaneous melanoma
Nuclear PTEN expression and clinicopathologic features in a population-based series of primary cutaneous melanoma
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DOI：
10.1002/ijc.10294
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发表时间：
2002-05-01
影响因子：
6.4
通讯作者：
Eng, C
中科院分区：
文献类型：
--
作者：
Whiteman, DC;Zhou, XP;Eng, C
10q23 上的 PTEN 肿瘤抑制基因的种系突变会导致 Cowden 综合征，这是一种遗传性错构瘤综合征，具有患乳腺癌、甲状腺癌和子宫内膜癌以及（有人认为）黑色素瘤的高风险。迄今为止，大多数强烈暗示 PTEN 与散发性黑色素瘤病因学相关的研究都依赖于细胞系、短期肿瘤培养物和非培养的转移性黑色素瘤。唯一报道黑色素瘤中 PTEN 蛋白表达的研究侧重于细胞质表达，主要是在转移样本中。为了确定 PTEN 如何影响原发性皮肤黑色素瘤的病因或进展，我们在 150 名原发性皮肤黑色素瘤患者的人群样本中对照临床和病理特征检查了细胞质和核 PTEN 表达。在 92 个可评估样本中，30 个细胞质 PTEN 蛋白表达没有或减少，其余 62 个 PTEN 表达正常。相比之下，84 个肿瘤没有核表达或核表达减少，8 个肿瘤的核 PTEN 表达正常。所研究的临床特征（例如 Clark 水平和 Breslow 厚度或阳光照射）均与细胞质 PTEN 表达水平无关。解剖部位 (p = 0.06) 和有丝分裂指数 (p = 0.02) 表明与核 PTEN 表达缺失相关。黑色素瘤不表达核 PTEN 或单独表达 p53，而不是同时表达两者，也存在相关性 (p = 0.02)。与转移性黑色素瘤相反，我们之前已经证明，几乎三分之二的肿瘤具有一定程度的 PTEN 失活，而只有三分之一的原发性黑色素瘤具有 PTEN 沉默。这表明 PTEN 失活是一个晚期事件，可能与黑色素瘤进展相关，而不是与起始相关。结合我们之前在甲状腺和胰岛细胞肿瘤中的观察，我们的数据表明 PTEN 的核质分配也可能在黑色素瘤进展中发挥作用。 (C) 2002 Wiley-Liss, Inc.
Germline mutations of the PTEN tumor-suppressor gene, on 10q23, cause Cowden syndrome, an inherited hamartoma syndrome with a high risk of breast, thyroid and endometrial carcinomas and, some suggest, melanoma. To date, most studies which strongly implicate PTEN in the etiology of sporadic melanomas have depended on cell lines, short-term tumor cultures and noncultured metastatic melanomas. The only study which reports PTEN protein expression in melanoma focuses on cytoplasmic expression, mainly in metastatic samples. To determine how PTEN contributes to the etiology or the progression of primary cutaneous melanoma, we examined cytoplasmic and nuclear PTEN expression against clinical and pathologic features in a population-based sample of 150 individuals with incident primary cutaneous melanoma. Among 92 evaluable samples, 30 had no or decreased cytoplasmic PTEN protein expression and the remaining 62 had normal PTEN expression. In contrast, 84 tumors had no or decreased nuclear expression and 8 had normal nuclear PTEN expression. None of the clinical features studied, such as Clark's level and Breslow thickness or sun exposure, were associated with cytoplasmic PTEN expressional levels. An association with loss of nuclear PTEN expression was indicated for anatomical site (p = 0.06) and mitotic index (p = 0.02). There was also an association for melanomas to either not express nuclear PTEN or to express p53 alone, rather than both simultaneously (p = 0.02). In contrast with metastatic melanoma, where we have shown previously that almost two-thirds of tumors have some PTEN inactivation, only one-third of primary melanomas had PTEN silencing. This suggests that PTEN inactivation is a late event likely related to melanoma progression rather than initiation. Taken together with our previous observations in thyroid and islet cell tumors, our data suggest that nuclear-cytoplasmic partitioning of PTEN might also play a role in melanoma progression. (C) 2002 Wiley-Liss, Inc.