Brod J M, Demasi Ana Paula Dias, Montalli V A, Teixeira L N, Furuse C, Aguiar M C, Soares A B, Sperandio M, Araujo V C
Department of Oral Pathology, São Leopoldo Mandic Institute and Research Center, Rua José Rocha Junqueira 13, Swift, Campinas, SP, 13045-755, Brazil.
State University of São Paulo, Araçatuba, SP, Brazil.
Virchows Arch. 2017 Dec;471(6):793-798. doi: 10.1007/s00428-017-2218-8. Epub 2017 Aug 28.
Polymorphous adenocarcinoma (PAC) is a malignant epithelial neoplasm that affects almost exclusively the minor salivary glands, generally described as having a relatively good prognosis. Aberrant nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) activation in tumor cells has been associated with induction of antioxidant enzymes, such as peroxiredoxin I (Prx I) and increased matrix metalloproteinase (MMP) expression. In this context, the aim of the present study was to evaluate the expression of Nrf2 and correlate it with Prx I and MMP-2 secretion in PAC. Thirty-one cases of PAC from oral biopsies were selected and immunohistochemically analyzed for Nrf2 and Prx I. MMP-2 quantification was performed on primary cell cultures derived from PAC. Oral squamous cell carcinoma (OSCC) cell cultures were used as control. A high immunoexpression of Nrf2 was observed in both the cytoplasm and the nucleus of neoplastic cells from PAC. Nuclear staining for Nrf2 suggested its activation in the majority of the PAC cells, which was confirmed by the high expression of its target gene, Prx I. Quantification of MMP-2 secretion showed lower levels in PAC cell cultures when compared to OSCC cell cultures (p < 0.05). In conclusion, although Nrf2 overexpression has been frequently associated with high-grade malignancies, such relationship is not infallible and, in fact, the opposite may occur in low-grade tumors, such as PAC of minor salivary glands.
多形性腺癌（PAC）是一种几乎仅累及小唾液腺的恶性上皮性肿瘤，通常被认为预后相对较好。肿瘤细胞中异常的核因子红细胞2（NF-E2）相关因子（Nrf2）激活与抗氧化酶如过氧化物酶I（Prx I）的诱导以及基质金属蛋白酶（MMP）表达增加有关。在此背景下，本研究的目的是评估Nrf2的表达，并将其与PAC中Prx I和MMP-2的分泌相关联。选取31例口腔活检的PAC病例，对其进行Nrf2和Prx I的免疫组织化学分析。对源自PAC的原代细胞培养物进行MMP-2定量分析。使用口腔鳞状细胞癌（OSCC）细胞培养物作为对照。在PAC肿瘤细胞的细胞质和细胞核中均观察到Nrf2的高免疫表达。Nrf2的核染色表明其在大多数PAC细胞中被激活，这通过其靶基因Prx I的高表达得到证实。与OSCC细胞培养物相比，PAC细胞培养物中MMP-2分泌的定量分析显示水平较低（p < 0.05）。总之，尽管Nrf2过表达常与高级别恶性肿瘤相关，但这种关系并非绝对，事实上，在低级别肿瘤如小唾液腺PAC中可能会出现相反的情况。
