Investigators at the Mount Sinai School of Medicine, Toronto, Canada, have been working on a potential correlation for aggressiveness and/or disease-free survival in thyroid cancer patients.
Paul G. Walfish, MD, FRCP
Investigators at the Mount Sinai School of Medicine, Toronto, Canada, have been working on determining whether or not PD-L1 expression levels and tissue (sub)localization may correlate with aggressiveness and/or disease-free survival in thyroid cancer. Paul G. Walfish, MD, FRCP presented this research, October 21, 2015, at the 15th Annual International Thyroid Congress, Laek Buena Vista, Florida.
Walfish et al examined PD-L1 expression using formalin-fixed paraffin-embedded tissue sections with antiPD-L1 rabbit polyclonal antibodies. A total of 200 patients with papillary thyroid cancer ranging from benign to aggressive subtypes were analyzed. Two different cytologists independently performed double-blind immunohistochemical scoring on these samples. A score of 1 to 4 was given based on the percentage of cells stained with a value of 4 denoted: >70% of the cells stained. The intensity of staining was tallied with a value ranging from 0 to 3, with 3 represented intense staining. The sum of intensity plus percentage measures was made for all samples. Both cytologists independently observed clear increases in PD-L1 signal in tissues that directly correlated with disease progression.
Coexpression of PD-L1 with thyroid transcription factor-1 proved detection predominately restricted to thyroid tissues, but PD-L1 was also notably detectable in lymphocytes. Accordingly, Walfish cautioned that one must be very careful when interpreting PD-L1 histology if there are signs of Hashimoto’s disease or lymphocytic thyroiditis because, even in the benign nodules, there is a high percentage of PD-L1containing cells.
More detailed analysis of PD-L1 subcellular localization also revealed a significantly greater amount of cytosolic PD-L1 in more aggressive thyroid cancers, with little change in nuclear PD-L1 levels. Kaplan Meier analysis of PD-L1 membrane-positive tumor cells revealed significantly shorter median disease free survival (DFS = 9.75 months) compared with PD-L1negative tumor cells (DFS = 166.5 months;P<.001).
Walfish described high PD-L1 expression associated with PTC aggressiveness and emphasized that this may be useful for identifying patients that will need more aggressive surveillance and therapy. When assessing PD-L1 expression, the coexisting lymphocytic infiltration due to autoimmune thyroid disease can lead to false-positive results.
Walfish stressed that PD-L1 histology suggests a possibility as a prognostic marker of disease aggressiveness, particularly for metastatic disease stages III and IV. Moreover these results justify the administration of antiPD-L1 immunotherapy in patients that are unresponsive to radioiodine or other chemotherapy measures.
In the question and answer that followed, one audience member asked about fine needle aspiration (FNA) biopsy as a means of obtaining tissue for analysis. Walfish elaborated that it would be nice to be able to perform this analysis with FNA biopsy, but it is not so easy because you have to rule out infiltrating lymphocytes. These studies were all done using formalin-fixed paraffin-embedded tissue sections.
Walfish P. G. Programmed death ligand 1 expression correlates with aggressive metastatic papillary thyroid carcinoma. Presented at the 15th International Thyroid Congress: Lake Buena Vista, Florida; October 21, 2015. Abstract #463.