2016
DOI: 10.1093/annonc/mdw289
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Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer

Abstract: The tumor microenvironments of paired primary lung cancers and brain metastases are significantly different, such that many of the metastases lose PD-L1 expression, lymphocyte infiltration or both with greater discrepancies over time. The spatial and temporal heterogeneity of PD-L1 expression may limit its use as a tissue-based predictive biomarker in lung cancer.

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Cited by 299 publications
(245 citation statements)
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“…A similar spatial and temporal heterogeneity has been described in other malignancies such as clear cell renal carcinoma, melanoma, and lung cancer. [38][39][40][41] This finding has implications for designing clinical trials and for retesting of metastatic neoplasms, which may be more or less accessible than their primary counterparts. This is particularly relevant for cSCC as the histologic material of the primary site may not be easily available for testing in many metastatic cases.…”
Section: Discussionmentioning
confidence: 99%
“…A similar spatial and temporal heterogeneity has been described in other malignancies such as clear cell renal carcinoma, melanoma, and lung cancer. [38][39][40][41] This finding has implications for designing clinical trials and for retesting of metastatic neoplasms, which may be more or less accessible than their primary counterparts. This is particularly relevant for cSCC as the histologic material of the primary site may not be easily available for testing in many metastatic cases.…”
Section: Discussionmentioning
confidence: 99%
“…A recent analysis has shown a spatial discordance of tumor cell PD-L1 expression in 14% between lung cancers and brain metastasis, and a nonstatistical significant temporal discordance of 11% in samples tested for expression between 6 months apart. 19 Utilizing a categorical cut-off has proven difficult and there is currently no consensus for this. However, the current rationale for choosing cut-off for determining on treatment options remains unclear and may vary depending on type of tumor tissue that is being assessed.…”
Section: F I G U R E 2 Examples Of Pd-l1 Staining In Tumor Tissuesmentioning
confidence: 99%
“…26 Advances in genetics have helped reveal the genetic complexity of melanoma and intratumoral heterogeneity. 27,28 In addition, TCR sequencing has shown that differences in T cell receptor residents within these lesions are greater than the genetic differences between individual metastases.…”
mentioning
confidence: 99%