Department of Otolaryngology, IUOPA, Hospital Universitario Central de Asturias, Oviedo, 33006 Asturias, Spain.
Hum Pathol. 2012 Nov;43(11):1894-901. doi: 10.1016/j.humpath.2012.01.016. Epub 2012 May 8.
Intestinal-type sinonasal adenocarcinoma represents 8% to 25% of all malignant sinonasal cancer and is etiologically related to occupational exposure to wood dust. Despite its clear etiology, the mechanisms behind the carcinogenic effects of wood dust are unclear. Because it is known that carcinogens can leave specific mutational fingerprints, we aimed to analyze the spectrum of TP53 mutations and to relate the findings to the wood dust etiology of the patients. Forty-four primary tumors were examined for TP53 mutations by direct sequencing. In addition, p53 protein expression was analyzed by immunohistochemistry using a tissue microarray consisting of 92 tumors. We report a frequency of 41% (18/44) TP53 mutations and 72% (66/92) p53 immunopositivity in intestinal-type sinonasal adenocarcinoma, significantly related to wood dust, but not to tobacco etiology. G→A transition (50%, 9/18 cases) was the most common alteration detected, almost exclusively found in nonsmokers, whereas G→T (27%, 5/18 cases) was detected in smokers only. These data point to wood dust exposure as the causal factor in the mutagenesis of TP53, possibly caused by reactive nitrogen species generated through a chronic inflammatory process.
肠型鼻腔鼻窦腺癌占所有恶性鼻腔鼻窦癌的 8%至 25%，其病因与职业性接触木尘有关。尽管病因明确，但木尘致癌作用的机制尚不清楚。因为已知致癌物会留下特定的突变指纹，所以我们旨在分析 TP53 突变的频谱，并将这些发现与患者的木尘病因联系起来。通过直接测序，我们对 44 例原发性肿瘤进行了 TP53 突变检测。此外，我们还使用包含 92 个肿瘤的组织微阵列通过免疫组化分析了 p53 蛋白的表达。我们报告肠型鼻腔鼻窦腺癌的 TP53 突变频率为 41%（18/44），p53 免疫阳性率为 72%（66/92），与木尘显著相关，但与烟草病因无关。我们检测到的最常见的突变是 G→A 转换（50%，18 例中的 9 例），几乎只发生在不吸烟者中，而 G→T（27%，18 例中的 5 例）仅发生在吸烟者中。这些数据表明，木尘暴露是 TP53 突变的因果因素，可能是通过慢性炎症过程产生的活性氮物种引起的。
