PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions

Histopathology. 2017 Sep;71(3):470-474. doi: 10.1111/his.13254. Epub 2017 Jun 29.

Abstract

Aims: PD-1/PD-L1 checkpoint immunotherapy has been proposed recently as a promising treatment in relapsed/refractory disease, used eventually in combination with traditional chemotherapy in different cancer settings. To date, no data are available concerning PD-L1 expression in ampulla of Vater carcinoma and its pre-invasive 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 seven of 26 (26.9%) invasive carcinomas and three of 50 (6.0%) dysplastic samples. Most of the PD-L1-positive tumours (seven of 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 eight invasive carcinomas did not show any evident epithelial or 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 significantly 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 the PD-1/PD-L1 axis in ampullary adenocarcinomas, and therefore this may also prompt consideration of checkpoint immunotherapy as a novel promising treatment for these tumours.

Keywords: PD-L1; ampulla of Vater; biomarkers; dysplasia.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Ampulla of Vater / immunology
  • Ampulla of Vater / pathology*
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / immunology
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology
  • Common Bile Duct Neoplasms / immunology
  • Common Bile Duct Neoplasms / pathology
  • Duodenal Neoplasms / immunology
  • Duodenal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Precancerous Conditions / immunology
  • Precancerous Conditions / pathology

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human