Programmed cell death-ligand 1 (PD-L1) overexpression in ampulla of Vater carcinoma and its pre-invasive lesions

Abstract

Aims

PD-1/PD-L1 checkpoint immunotherapy has recently been proposed as a promising treatment in relapsed/refractory disease, eventually used in combination with the traditional chemotherapy in different cancer settings. No data are still now available about PD-L1 expression in ampulla of Vater carcinoma and its preinvasive lesions.

Methods and results

We assessed the immunohistochemical expression of PD-L1 in a series of 26 ampullary adenocarcinomas, 50 ampullary dysplastic lesions, and 10 normal duodenal mucosa samples. Moreover, in all cases DNA mismatch repair proteins status was investigated. PD-L1 was expressed in 7/26 (26.9%) invasive carcinomas and 3/50 (6.0%) dysplastic samples. Most of the PD-L1 positive tumors (7/10) were intestinal-type and poorly differentiated (G3). The number of PD-L1-positive stromal lymphoid cells was significantly higher in dysplastic and invasive lesions than in the normal samples (p=0.011). Nineteen dysplastic lesions and 8 invasive carcinomas did not show any evident epithelial nor stromal PD-L1 expression. Four of the carcinomas were mismatch-repair-deficient and two of these were PD-L1 positive. Furthermore, mismatch-repair-deficient lesions showed a significant higher average of PD-L1-positive stromal lymphoid cells than those of neoplastic PD-L1-negative samples (62.8 versus 21.6; p< 0.001).

Conclusions

The present results suggest a role of PD-1/PD-L1 axis in ampullary adenocarcinomas and therefore it may prompt to consider checkpoint immunotherapy as a novel promising treatment also for these tumors.

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