Lee Carolyn, Ramirez James A, Guitart Joan, Diaz Leslie K
Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Cutan Pathol. 2008 Nov;35(11):989-94. doi: 10.1111/j.1600-0560.2007.00939.x. Epub 2008 Jun 4.
Cancer chemoprevention using nonsteroidal anti-inflammatory drugs is frequently attributed to cyclooxygenase-2 (COX-2) inhibition, although recent studies suggest that peroxisome proliferator-activated receptor gamma (PPARgamma) may also be involved. While surgical excision remains the treatment mainstay for localized malignant melanoma, certain high-risk patients may benefit from adjunctive chemotherapy. In this study, we compared COX-2 and PPARgamma immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers.
COX-2 and PPARgamma immunohistological staining was performed and reviewed in 99 melanocytic lesions, including 38 benign nevi, 32 primary melanomas and 29 metastatic melanomas.
There was a significant increase in both COX-2 and PPARgamma immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPARgamma-immunopositive cells. They were also more likely to express COX-2 than primary melanomas. Neither COX-2 nor PPARgamma expression was associated with a specific pathologic subtype.
COX-2 and PPARgamma may help modulate the progression of melanocytic precursor lesions to disseminated malignant melanoma. As such, they may serve as candidate substrates for targeted cancer therapies and may be particularly useful as adjuncts to surgery.
使用非甾体抗炎药进行癌症化学预防通常归因于环氧合酶-2(COX-2)抑制作用,尽管最近的研究表明过氧化物酶体增殖物激活受体γ(PPARγ)可能也参与其中。虽然手术切除仍然是局限性恶性黑色素瘤的主要治疗方法,但某些高危患者可能从辅助化疗中获益。在本研究中,我们比较了良性痣、原发性黑色素瘤和转移性黑色素瘤中COX-2和PPARγ的免疫组织化学染色,以帮助预测靶向这些标志物的化合物的有效性。
对99个黑素细胞性病变进行了COX-2和PPARγ免疫组织化学染色并进行分析,其中包括38个良性痣、32个原发性黑色素瘤和29个转移性黑色素瘤。
与良性痣相比,黑色素瘤中COX-2和PPARγ免疫染色均显著增加。转移性黑色素瘤更有可能有更多PPARγ免疫阳性细胞。它们也比原发性黑色素瘤更有可能表达COX-2。COX-2和PPARγ的表达均与特定的病理亚型无关。
COX-2和PPARγ可能有助于调节黑素细胞前体病变向播散性恶性黑色素瘤的进展。因此,它们可能作为靶向癌症治疗的候选底物,并且作为手术辅助手段可能特别有用。