Lo Muzio Lorenzo, Campisi Giuseppina, Giovannelli Lucia, Ammatuna Pietro, Greco Immacolata, Staibano Stefania, Pannone Giuseppe, De Rosa Gaetano, Di Liberto Chiara, D'Angelo Matteo
Institute of Dental Sciences, University of Ancona, Via Toti 4, 60100, Italy.
Oral Oncol. 2004 Aug;40(7):736-41. doi: 10.1016/j.oraloncology.2003.11.011.
HPV has been thought to be involved in the development of several oral diseases, such as premalignant mucosal lesions and oral carcinoma. Survivin is a recently characterized IAP protein, which is abundantly expressed in most solid and haematological malignancies, but undetectable in normal adult tissues. Aim of this study was to investigate survivin expression and HPV presence in oral premalignant lesions and oral carcinoma. 47 samples of oral tissue including 11 squamous cell carcinomas (OSCC), 16 oral leukoplakias (OL) and 20 normal oral mucosa specimens, after investigation of HPV presence by nested PCR (consensus MY/GP primers) and viral genotype identification by direct sequencing were investigated by immunohistochemistry to detect survivin expression. Survivin expression was evident in 4/7 (57.1%) HPV+ and 4/4 (100%) HPV- OSCC, 6/7 (85.7%) HPV+ and 5/9 (55.5%) HPV- OL and in 0/20 (0%) control samples. Data showed high levels of survivin expression in HPV-positive SCCs, even if mean values were lower than HPV-negative ones, which in particular showed survivin expression in 100% of cases. Conversely, survivin expression was greater in HPV+ precancerous lesions than in HPV- ones. Our findings suggest that survivin may be involved in HPV- mediated deregulation during maturation of squamous epithelium through modulation of the apoptotic processes and, conversely, HPV may have a direct or indirect effect on the regulation of the survivin expression level. In particular, the results of this study suggest distinguishing between cancerous and precancerous oral lesions with respect to survivin expression when HPV infection is present. The most unfavourable behaviour is likely to be for the HPV- OSCC.
人乳头瘤病毒(HPV)被认为与多种口腔疾病的发生有关,如癌前黏膜病变和口腔癌。生存素是一种最近被鉴定的凋亡抑制蛋白(IAP),在大多数实体瘤和血液系统恶性肿瘤中大量表达,但在正常成人组织中无法检测到。本研究的目的是调查生存素在口腔癌前病变和口腔癌中的表达以及HPV的存在情况。通过巢式聚合酶链反应(共识MY/GP引物)检测HPV的存在,并通过直接测序鉴定病毒基因型后,对47份口腔组织样本进行免疫组织化学检测,以检测生存素的表达,其中包括11例鳞状细胞癌(OSCC)、16例口腔白斑(OL)和20例正常口腔黏膜标本。生存素表达在4/7(57.1%)HPV阳性和4/4(100%)HPV阴性的OSCC中明显,在6/7(85.7%)HPV阳性和5/9(55.5%)HPV阴性的OL中明显,而在0/20(0%)的对照样本中未检测到。数据显示,HPV阳性的鳞状细胞癌中生存素表达水平较高,即使平均值低于HPV阴性的病例,后者在100%的病例中均显示有生存素表达。相反,HPV阳性的癌前病变中生存素表达高于HPV阴性的病变。我们的研究结果表明,生存素可能通过调节凋亡过程参与HPV介导的鳞状上皮成熟过程中的失调,相反,HPV可能对生存素表达水平的调节有直接或间接影响。特别是,本研究结果表明,当存在HPV感染时,在生存素表达方面区分癌性和癌前口腔病变。最不利的情况可能是HPV阴性的OSCC。