Ibrahim S O, Bertelsen B, Kalvenes M B, Idris A M, Vasstrand E N, Nilsen R, Johannessen A C
Department of Odontology-Oral Pathology and Forensic Odontology, The Gade Institute, University of Bergen, Norway.
APMIS. 1998 Oct;106(10):959-69. doi: 10.1111/j.1699-0463.1998.tb00246.x.
In stratified squamous epithelia, altered expression of keratins (Ks) is one possible marker of malignant potential. In the epithelium of the uterine cervix, presence of human papillomaviruses (HPVs) is increasingly regarded as a marker of risk for cervical cancer. However, a similar role in oral cancer and precancer remains controversial. To address these questions, formalin-fixed, paraffin-embedded oral carcinomas from Sudanese snuff dippers (n=14) and oral carcinomas from Sudanese (n=14), Swedish (n=19) and Norwegian (n=41) non-snuff dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies. HPV infection was searched for in all the carcinomas by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. Carcinomas from Sudanese (snuff dippers/non-snuff dippers) were also examined for HPV infection by polymerase chain reaction (PCR) using the general HPV primers GP5+/GP6+. For the oral carcinomas from snuff dippers, moderate to intense expression of K13 (71%; 10/14), K14 (86%; 12/14) and K19 (93%; 13/14) was found. For the oral carcinomas from non-snuff dippers, weak to moderate expression of K13 (64%; 47/74), K14 (43%; 32/74) and K19 (45%; 33/74) was found. HPV DNA was not detected in any of the carcinomas from three countries when examined by ISH. The Sudanese (from snuff dippers/non-snuff dippers) oral carcinomas were also negative for HPV DNA with the PCR. The present study shows that (i) there is a high level of expression of K13, K14 and K19 in oral carcinomas from snuff dippers compared to those from non-snuff dippers, (ii) this high level of expression may arise from dysregulation of keratinocyte proliferation and maturation caused by damaging effects of snuff, (iii) the HPV genome is not found in Sudanese (snuff dippers/non-snuff dippers), Swedish or Norwegian oral carcinomas, and (iv) this may suggest that these viruses do not play a prominent role in the aetiology of oral carcinomas from these countries.
在复层鳞状上皮中，角蛋白（Ks）表达改变是恶性潜能的一种可能标志物。在子宫颈上皮中，人乳头瘤病毒（HPV）的存在日益被视为宫颈癌风险的标志物。然而，其在口腔癌及癌前病变中的类似作用仍存在争议。为解决这些问题，我们采用单克隆抗体免疫组化法，检测了来自苏丹鼻烟使用者的福尔马林固定、石蜡包埋口腔癌（n = 14）以及来自苏丹（n = 14）、瑞典（n = 19）和挪威（n = 41）非鼻烟使用者的口腔癌中13、14和19型角蛋白的表达。使用HPV OmniProbe混合探针和ViraType探针通过原位杂交（ISH）在所有癌组织中检测HPV感染情况。还使用通用HPV引物GP5+/GP6+通过聚合酶链反应（PCR）检测苏丹（鼻烟使用者/非鼻烟使用者）的口腔癌中的HPV感染情况。对于鼻烟使用者的口腔癌，发现K13（71%；10/14）、K14（86%；12/14）和K19（93%；13/14）呈中度至强表达。对于非鼻烟使用者的口腔癌，发现K13（64%；47/74）、K14（43%；32/74）和K19（45%；33/74）呈弱至中度表达。通过ISH检测时，在来自三个国家的任何癌组织中均未检测到HPV DNA。苏丹（鼻烟使用者/非鼻烟使用者）的口腔癌经PCR检测HPV DNA也为阴性。本研究表明：（i）与非鼻烟使用者的口腔癌相比，鼻烟使用者的口腔癌中K13、K14和K19表达水平较高；（ii）这种高表达水平可能源于鼻烟的损害作用导致角质形成细胞增殖和成熟失调；（iii）在苏丹（鼻烟使用者/非鼻烟使用者）、瑞典或挪威的口腔癌中未发现HPV基因组；（iv）这可能表明这些病毒在这些国家口腔癌的病因学中不发挥突出作用。
