PD-L1 Expression in Anal Intraepithelial Neoplasia Versus. Invasive Squamous Cell Carcinoma

Abstract Introduction/Objective Upregulation of programmed death-ligand 1 (PD-L1), an immunoregulatory protein is associated with adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in anal lesions. In this study we compare PD-L1 expression in anal squamous intraepithelial lesions (SIL/AIN) with that in invasive squamous cell carcinoma (ISCC) Methods After IRB approval, formalin-fixed paraffin embedded sections from 84 patients (51 with ISCC and 32 without ISCC), from 2010–2018, were immunostained for PD-L1 (Dako 22C3 monoclonal antibody). These included 15 cases with normal mucosa, 60 cases with low grade squamous intraepithelial lesion (LSIL/AIN 1), 52 cases with high grade intraepithelial lesion (HSIL/AIN2-3), and 51 cases of ISCC. Overall tumor proportion score of > 1% tumor cells with partial or complete membrane staining was interpreted as PD-L1 positive (PD-L1 +). Results PD-L1 was positive in 18/51 (35%) and negative in 33/51 (65%) cases of ISCC. Staining was heterogenous in all PD-L1 positive cases, with invasive foci that were negative to 100% positive. Tumor proportion score ranged from 1% to 50%. No PD-L1 membrane positivity was seen in any of the normal mucosa, LSIL/AIN 1, and HSIL/AIN 2-3. Even in cases of microinvasive or invasive carcinoma, PD-L1 positivity was seen only in the invading malignant cells and not in the overlying or adjacent HSIL. One case showed aberrant nuclear staining in 10% of cells in LSIL and HSIL. About 25% of cases showed non-specific basal granular cytoplasmic staining in normal mucosa, LSIL, and HSIL, that correlated with the presence of melanin. Cases with normal mucosa, LSIL/AIN 1, and HSIL/AIN 2-3, were equally distributed between cases with no invasive carcinoma, PD-L1 positive ISCC, and PD-L1 negative ISCC. Conclusion No PD-L1 positivity (membrane staining) was present in normal mucosa or anal squamous intraepithelial lesion/anal intraepithelial neoplasia in our study. Any nuclear staining or granular cytoplasmic staining should not be interpreted as PD-L1 positivity. PD-L1 was only positive in a subset (35%) of invasive squamous cell carcinoma. The expression of PD-L1 is likely to be associated with an invasive malignant process and is a potential target for therapy with PD-L1 inhibitors.