Histopathological varieties of oral carcinomain situ: Diagnosis aided by immunohistochemistry dealing with the second basal cell layer as the proliferating center of oral mucosal epithelia

Abstract

To make reproducible diagnoses for oral carcinoma in situ (CIS), combined immunohistochemistry directed at the positioning of squamous cell proliferation (Ki-67) and differentiation (keratin (K) 13 and K19) was used, both of which support histological evaluations by providing biological evidence. 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. When the definition was applied, surgical margins in 172 recurrent cases were shown to contain CIS (39.4%) and squamous cell carcinoma (55.8%), indicating that the new diagnostic criteria for CIS reflected clinical behaviors of the cases. The results indicate that oral CIS contain more histological variations, especially those with definite keratinization, than what had been previously defined.

Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections

“…Normal epithelia were also confirmed by the presence of K19 in the first basal cells and Ki-67-positive ( þ ) cells in the second basal layer as described previously (not shown). 5 Mild and moderate epithelial dysplasia (Figure 1d) showed basically similar staining patterns to those of normal epithelia for K13 (Figure 1e) and K16 (Figure 1f). In dysplasia, K19 disappears from the basal cells, and Ki-67 þ cells were expansively located towards the first and third basal and upper layers (not shown).…”

“…In dysplasia, K19 disappears from the basal cells, and Ki-67 þ cells were expansively located towards the first and third basal and upper layers (not shown). 5 Two types of CIS were demonstrated in Figure 1: basaloid type (Figure 1g-i) and differentiated type (Figure 1j-l). 5 CIS is not yet invasive, whereas its immunohistochemical features are the same as those of SCC (Figure 1m-o).…”

“…5 Two types of CIS were demonstrated in Figure 1: basaloid type (Figure 1g-i) and differentiated type (Figure 1j-l). 5 CIS is not yet invasive, whereas its immunohistochemical features are the same as those of SCC (Figure 1m-o). Neither K13 (Figure 1k and n) nor K19 (not shown) were positive, whereas K16 (Figure 1l and o) and K17 (not shown) were reciprocally positive with an expansion of Ki-67 þ cells including the first basal layer (not shown).…”

“…Expansions of the Ki-67-positive ( þ ) cell proliferating center start to replace the first basal cells in the lower direction, as well as the prickle cells in the upper direction, resulting in gradual losses of K19 and K13 in those cells, which should represent such neoplastic conditions as epithelial dysplasia and carcinoma in situ (CIS). 5 In particular, a total loss of K13 in the prickle cell layer should be one of the most important histochemical markers for the diagnosis of differentiated types of oral CIS, because the prickle cells of CIS are unable to be distinguished from the normal prickle cells on HE sections.…”

“…[4][5][6][8][9][10][11][12][13][14] Regarding the disappearance of K13 in laryngeal squamous cell carcinomas (SCCs) with definite keratinization tendencies, masking or modification of K13 antigenic sites due to some dysfunction of the K13 gene has been suggested. 11 However, there has been no investigation on the K13 gene expression levels in the oral squamous epithelial lesions lacking the immunohistochemical expression of the K13 protein.…”