MIXED TUMOR, POLYMORPHOUS LOW-GRADE ADENOCARCINOMA AND ADENOID CYSTICCARCINOMA OF THE SALIVARY-GLAND - PATHOGENIC IMPLICATIONS AND DIFFERENTIAL-DIAGNOSIS BY KI-67 (MIB1), BCL2, AND S-100 IMMUNOHISTOCHEMISTRY

The morphologic distinction between salivary gland mixed tumor (MT), p olymorphous low-grade adenocarcinoma (PLGA), and adenoid cystic carcin oma (ACC) can be difficult, espe cially on small amounts of material. To determine whether immunohistochemical features might help in this d ifferential, we characterized the staining pattern for these three tum ors using antibodies to Ki-67 (MIB1), BCL2, p53, and S-100 proteins. W e immunostained 34 MTs, 30 PLGAs, and 35 ACCs. The ACCs had significan tly more tumor cells positive for Ki-67 (MIB1) (medians 20-50%) than b oth PLGAs (median, 1.0%) and MTs (median, 1.0%) (each p value < 0.0001 ). Within the group of ACCS, the percentage of positive staining corre lated with increasing histologic grade (grade 1 = 20% and grade 2 = 30 % compared with grade 3 = 50%; each p < 0.01). S-100 immunostaining wa s strongly positive in both MTs (median, 75% tumor cells positive) and PLGAs (median, 82.5%), but it was relatively low in ACC relative to M T and PLGA (medians, 1-5.5%; p values from 0.015-<0.000001). BCL2 was positive in all tumors, although staining intensity was significantly greater in the ACCs (p values from 0.065-<0.000001). p53 immunostainin g was absent to low (<2% of tumor cells) in MTs and PLGAs, a value sig nificantly less than the immunostaining found in ACCs (p values from 0 .048-0.00013). Within the ACCS, p53-positive cells appeared to increas e significantly with increasing histologic grade (for grade 1 vs. grad e 2 ACC, p = 0.018). In conclusion, MT and PLGA showed low Ki-67 (MIB1 ) and p53 immunostaining but frequent and strong S100 protein immunore activity. ACC showed relatively high Ki-67 (MIB1) and more intense BCL 2 immunoreactivity, and the percentage of p53 immunostaining increased with increasing ACC histograde. S100 was less intense and less freque nt in ACC compared with MT and PLGA. These findings suggest that Ki-67 (MIB1), S100, and BCL2 immunohistochemical stains are useful for sepa rating ACC from PLGA and MT. Also, deregulation of proliferation and p ossible mutations in p53 may contribute to the greater malignancy of A CC compared with MT and PLGA.