Expression of PD-1 in Non-Small Cell Carcinoma of the Lung
Anna P Matynia, Michelle L Wallander, Sheryl Tripp, Wallace L Akerley, Michael B Cohen. University of Utah, Salt Lake City, UT; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT
Background: Despite advances in treatment, lung cancer remains a leading cause of cancer related mortality in the United States. Advances in cancer immunotherapy, which attempts to stimulate the host immune system to reject tumors, have the potential to improve outcomes. Blockade of immune checkpoints, including the programmed cell death protein 1 (PD-1) pathway, is a new target for cancer immunotherapy. Interaction of the PD-1 receptor on peripheral T-lymphocytes with its ligands (PD-L1 and PD-L2), which are expressed in peripheral tissues and some cancers, inhibits T-cell function and subsequently leads to immune system evasion. Preliminary trials of anti-PD1 and anti-PD-L1 antibodies showed promising results in patients with non-small cell carcinoma of the lung (NSCLC). An objective response was observed in 18% and 10% of heavily pretreated NSCLC patients, following anti-PD1 and anti-PD-L1 antibody therapy, respectively. Patients with squamous cell carcinoma (SCC) had slightly better response rates. It is essential to identify suitable immunotherapy biomarkers in order to identify patients likely to respond to such therapies.
Design: We examined 45 cases of adenocarcinoma (AC) (excision and biopsy specimens) and 19 cases of SCC (excision specimens) with available formalin-fixed, paraffin-embedded tissue blocks. All cases were stained for PD-1 (polyclonal, R&D Systems) using standard immunohistochemical techniques. Staining in the carcinoma cells and infiltrating lymphocytes were scored separately. Carcinoma cells were scored as: 0 (negative) to 3+ (strongly positive); and PD-1 positive lymphocytes as: 0 (absent), 1 (rare), and 2 (easily identifiable).
Results: All ACs were negative for PD-1 staining in the tumor cells. The number of infiltrating PD-1 positive lymphocytes varied from absent in 15 cases, rare in 19 cases, to easily identifiable in 12 cases. Only one case of SCC (∼5%) showed 1+ staining for PD-1 in the tumor cells and also had easily identifiable PD-1 positive infiltrating lymphocytes. Of the remaining SCCs, infiltrating PD-1 positive lymphocytes were absent in 7 cases, rare in 3 cases, and easily identifiable in 8 cases.
Conclusions: In NSCLC, PD-1 expression on tumor cells is rare, 5% in SCC. PD-1 positive infiltrating lymphocytes are present in 67% and 63% of AC and SCC of the lung, respectively. PD-L1 and PD-L2 expression needs to be evaluated and correlated with PD-1 expression, and is being evaluated.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 292, Monday Morning