口腔鳞状上皮癌前病变IHC研究文献报导可以用Ki-67、p53、p63、p73、CK13、CK19来帮助鉴别单纯增生、异型增生、原位癌。形态学诊断异性增生根据上皮结构和细胞学异型，但是在增生和轻度异型增生、轻度与中度异型增生、高度异型增生与原位癌并没有绝对的分界线。IHC可比较客观的揭示细胞增殖和分化的异常和程度。请参考下列文献：
1）Kobayashi T, Maruyama S, Cheng J, et al.
Histopathological varieties of oral carcinoma in situ: Diagnosis aided by immunohistochemistry dealing with the second basal cell layer as the proliferating center of oral mucosal epithelia.
Pathol Int. 2010;60:156-66.

Normal/hyperplastic epithelia was defined by K19+ cells only in the first basal layer, K13+ cells in the third basal and upper layers, and sporadic Ki-67+ cells in the second basal layer. These profiles indicated that a proliferating center of the oral epithelium is located in the parabasal cell layer, and K19 and K13 can be regarded as markers for basal and prickle cells, respectively. Epithelial dysplasia was characterized by irregular stratification of Ki-67+ cells and the absence of K19/K13 in proliferating cells. Irregular emerging of K19+ and K13+cells in proliferating foci with unique stratification of atypical Ki-67+ cells indicated CIS.

2.Angiero F, Berenzi A, Benetti A, et al. Expression of p16, p53 and Ki-67 proteins in the progression of epithelial dysplasia of the oral cavity. Anticancer Res. 2008;28:2535-9.

BACKGROUND: The overexpression of the protein products of genes associated with the cell cycle tumour protein53 (p53), cyclin-dependent kinase inhibitor 2A (p16) and antigen identified by monoclonal antibody Ki-67 (Ki-67) is apparently of great significance. This study evaluated the immunohistochemical expression of these proteins in precancerous lesions and in carcinoma of the oral cavity.

MATERIALS AND METHODS: The nuclear expression of p53 and Ki-67 and nuclear and/or cytoplasmic expression of p16 protein was examined in 54 biopsy specimens from the oral cavity obtained over a period of 3 years. The samples included 18 cases of normal/hyperplastic mucosa, 25 cases of dysplasia and 11 cases of invasive squamous cell carcinoma. The specimens were grouped into three categories: 1 = no or mild dysplasia, 2 = moderate or severe dysplasia, and 3 = invasive carcinoma.

RESULTS:

p16 was negative in all the group 1 specimens, while both p53 and Ki-67,when present, were limited to the cells of the basal layer.

In the group 2 specimens, the number of p16-, p53-, and Ki-67-positive cells increased as the grade of dysplasia progressed.

In group 3 (invasive carcinomas), p53 and p16 expression occurred respectively in 81.8% and 54.5% of cases, while Ki-67 was elevated in all the cases.

CONCLUSION: The expression of the cell-cycle proteins p16 and p53 in the dysplastic epithelium, in association with Ki-67, may represent significant markers to recognize evolution of precancerous disease in the oral cavity and to improve identification of the degree of dysplasia.

 鳞状上皮中-重度异型增生，局灶重度异型增生（符合原位鳞癌)。