Erika Egal

Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.

Lipid droplets are involved in the process of high-grade transformation of adenoid cystic carcinoma

these cases, strong expression of PD-L1 by macrophages was a striking feature (Figure 1); three spMSIH tumours among these also showed membranous PD-L1 immunostaining of the tumour cells. By contrast, considerably less macrophage infiltration was seen in the five MSS tumours with moderate or highdegree tumour budding and, notably, in each case membranous PD-L1 immunostaining was observed in at least some tumour buds (Figure 2), although with low frequencies (<1% of the tumour buds). Applying the classification of cancers outlined by Teng et al., our observations suggest ‘adaptive immune resistance’ in microsatellite-unstable and some macrophage-rich microsatellite-stable colorectal carcinomas. This contrasts with ‘immunological ignorance’ in the microsatellite-stable and macrophage-poor colorectal carcinomas that, however, are apparently capable of mounting an ‘intrinsic induction’ of PD-L1 in some tumour buds.