Regezi J A, McMillan A, Dekker N, Daniels T E, Silverman S, Schoelch M, Ziober B L
Department of Stomatology, UCSF, USA.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Aug;86(2):196-202. doi: 10.1016/s1079-2104(98)90125-1.
Extranodal oral lymphomas, seen with increasing frequency in HIV infection, may have dysfunctional apoptotic mechanisms that favor tumor progression. The purpose of this study was to evaluate extranodal lymphomas from HIV-positive patients for expression of apoptosis-associated proteins. Correlations were made with 10 histologically comparable extranodal lymphomas from HIV-negative patients and 6 hyperplastic lymph nodes from otherwise healthy young adults. Formalin-fixed tissue sections were immunohistochemically stained for apoptosis-associated proteins (Bcl-2, Bcl-x, Bax, Bak, p53, MDM2, BHRF). In situ hybridization was also done on deparaffinized sections for Epstein-Barr virus EBER mRNA. Eighteen consecutive oral lymphomas were studied in HIV/AIDS-positive patients. Four of 5 intermediate-grade lymphomas expressed Bcl-2 to a greater degree than did high-grade lymphomas (4 of 13). Most lymphomas were positive for Bcl-x and Bax, and few expressed Bak. The staining patterns for these proteins were similar to those seen in HIV-negative patients. Staining patterns were relatively consistent in the hyperplastic lymph nodes, whereas such patterns were irregular in lymphomas. Positive p53 staining was seen in 11 of 18 HIV-positive cases; 9 of these were also MDM2-positive. Double stains suggested that both p53 and MDM2 proteins were expressed in the same cells in these nine cases. Epstein-Barr virus-EBER mRNA was detected in 14 of 18 cases and in 3 of 10 cases from HIV-negative patients. BHRF staining was evident in only a few cells of three HIV-positive lymphomas. The irregular expression of Bcl-2, Bcl-x, Bax, and Bak in oral lymphomas indicates dysfunctional apoptotic mechanisms in these tumors. Bcl-2 staining differs with tumor grade. Positive staining for p53 and MDM2 proteins is a notable feature of lymphomas in HIV-positive patients and may relate to binding of MDM2 to wild-type p53. Epstein-Barr virus is more commonly associated with oral lymphomas in HIV-positive patients, although the Epstein-Barr virus-produced protein BHRF, which has Bcl-2-like activity, is minimally expressed.
结外口腔淋巴瘤在HIV感染中愈发常见，其凋亡机制可能存在功能障碍，这有利于肿瘤进展。本研究旨在评估HIV阳性患者的结外淋巴瘤中凋亡相关蛋白的表达情况。将其与10例组织学上可比的HIV阴性患者的结外淋巴瘤以及6例来自健康年轻成年人的增生性淋巴结进行相关性分析。用福尔马林固定的组织切片进行凋亡相关蛋白（Bcl-2、Bcl-x、Bax、Bak、p53、MDM2、BHRF）的免疫组织化学染色。还对脱石蜡切片进行原位杂交检测爱泼斯坦-巴尔病毒EBER mRNA。对18例连续的HIV/AIDS阳性患者的口腔淋巴瘤进行了研究。5例中等级别淋巴瘤中有4例Bcl-2表达程度高于高等级淋巴瘤（13例中的4例）。大多数淋巴瘤Bcl-x和Bax呈阳性，很少表达Bak。这些蛋白的染色模式与HIV阴性患者中所见相似。增生性淋巴结中的染色模式相对一致，而淋巴瘤中的染色模式不规则。18例HIV阳性病例中有11例p53染色呈阳性；其中9例MDM2也呈阳性。双重染色表明在这9例病例中p53和MDM2蛋白在同一细胞中表达。18例病例中有14例检测到爱泼斯坦-巴尔病毒-EBER mRNA，10例HIV阴性患者的病例中有3例检测到。仅在3例HIV阳性淋巴瘤的少数细胞中可见BHRF染色。口腔淋巴瘤中Bcl-2、Bcl-x、Bax和Bak的不规则表达表明这些肿瘤中凋亡机制存在功能障碍。Bcl-2染色因肿瘤分级而异。p53和MDM2蛋白的阳性染色是HIV阳性患者淋巴瘤的一个显著特征，可能与MDM2与野生型p53的结合有关。爱泼斯坦-巴尔病毒与HIV阳性患者的口腔淋巴瘤更常相关，尽管具有Bcl-2样活性的爱泼斯坦-巴尔病毒产生的蛋白BHRF表达极少。
