Multivariate analyses of Ki‐67, cytokeratin 13 and cytokeratin 17 in diagnosis and prognosis of oral precancerous lesions

Abstract

BACKGROUND: Ki-67, cytokeratin 13, and/or cytokeratin 17 detection by immunohistochemistry has been reported to be useful for the diagnosis of oral precancerous lesions. However, the use of these markers remains controversial because of the lack of appropriately designed statistical studies. We assessed the hypothesis that Ki-67, cytokeratin 13, or cytokeratin 17 immunohistochemistry could facilitate the diagnosis of oral precancerous lesions and/or predict prognosis. METHODS: Epithelial dysplasia was classified as low grade (none or mild dysplasia) or high grade (moderate dysplasia, severe dysplasia, or carcinoma in situ). This study included 58 low-grade and 36 high-grade dysplasia cases. We used logistic regression to assess the diagnostic values of Ki-67, cytokeratin 13, and cytokeratin 17 for high-grade dysplasia. Correlations between these markers and the prognosis of oral atypical epithelium were assessed using the Cox proportional hazards model. RESULTS: Ki-67 overexpression and cytokeratin 13 loss were independent diagnostic markers for high-grade dysplasia (odds ratios, 1.92 and 2.53; 95% confidence intervals, 1.03-3.58, and 1.19-5.38, respectively). The area under the curve of Ki-67 was 0.73 and that of cytokeratin 13 was 0.72. However, the combination of Ki-67 and cytokeratin 13 yielded the area under the curve of 0.78. Ki-67 overexpression was significantly associated with recurrence and/or malignant transformation of oral atypical epithelium (hazard ratio, 7.25; 95% confidence interval, 1.07-48.92).CONCLUSIONS: Ki-67 overexpression and cytokeratin 13 loss may be useful for distinguishing oral precancerous lesions from reactive atypical epithelium. Moreover, Ki-67 overexpression may be a risk factor for recurrence and/or malignant transformation of oral atypical epithelium.

A study of Ki-67 expression and its clinicopathological determinants in nondysplastic oral leukoplakia

“…[71019] The previous literature on Ki-67 expression demonstrated the range of positivity for oral dysplastic epithelia from 13.5% to 51.2% and for oral SCC from 25% to 74.6%. [67891115] On the other end, many earlier studies and also this presently discussed study of ours have revealed that the lesions lacking any histopathological evidence of dysplasia may immunohistochemically express high and abnormal proliferative activity. [911] These OLs carry a significant potential to develop into SCC and should be managed in the same way as the corresponding grades of dysplasia.…”

“…[26] Yagyuu et al . [7] examined the OL patches from 94 Japanese patients and correlated the subepithelial lymphocytic infiltration with various grades of epithelial dysplasia as well as Ki-67 expression. They noticed that although there is an apparent tendency of higher subepithelial lymphocyte infiltration with increasing grades of dysplasia, such association did not manage any statistical significance.…”

“…Even these individual immunomarkers can be utilized as independent predictors for the dysplasia. [67]…”

“…[9] However, the earlier studies emphasizing on the diagnostic/prognostic competency as well as on scoring/labeling indices (LIs) of Ki-67 were mostly attributed to the comparative evaluation through various grades of dysplasia up to squamous cell carcinoma (SCC). [67891011] In this context, the present study aimed at evaluating the Ki-67 expression in the OL cases, which specifically did not feature any evidence of dysplasia on routine histopathology. Furthermore, an attempt was made to correlate various clinicopathological factors with the LI of Ki-67 in these cases.…”

Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17

“…Loss of CK13 along with expression of CK17 has been reported in (high-grade) oral epithelial dysplasia [15–17]. Increased expression of CK17 has been reported for dVIN [14], but CK13 has not yet been explored for this lesion.…”