Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a sur
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ORIGINAL ARTICLE
Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement Phillip M. Kemp Bohan1 · Robert C. Chick1 · Annelies T. Hickerson1 · Lynn M. Messersmith2 · Grant M. Williams2 · Jessica L. Cindass1 · Jamie Lombardo2 · Ryan Collins2 · Robert O. Brady2 · Diane F. Hale1 · George E. Peoples3 · Timothy J. Vreeland1 · Guy T. Clifton1 Received: 3 March 2020 / Accepted: 26 October 2020 © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract Background Colorectal cancer (CRC) tumor microenvironment (TME) characteristics, such as tumor infiltrating lymphocyte (TIL) densities and PD-L1 status, are predictive of recurrence, disease-free survival, and overall survival. In many malignancies, TME characteristics are also predictive of response to immunotherapy. As window of opportunity studies using neoadjuvant immunotherapy become more common and treatment guidelines incorporate TME features, accurate assessment of the pre-treatment TME using the biopsy specimen is critical. However, no study has thoroughly evaluated the correlation between the TMEs of the biopsy and resection specimens. Methods We conducted a retrospective analysis of patients with stage I–III CRC with matched biopsy and resection specimens. CD3+, CD4+, CD8+, and FoxP3+ lymphocyte populations at the center of tumor (CT) and invasive margin (IM) and tumor PD-L1 status in the biopsy and resection specimens were evaluated. TIL populations were compared using Mann– Whitney U tests or Student’s t tests and correlated using Pearson r. Results CD3+ and CD4+ densities were significantly higher in the CT of the biopsy relative to the resection specimen Comparing biopsy and resection specimens, no TIL population at either the CT or IM had a correlation coefficient > 0.5. Determining PD-L1 status based on biopsy tissue resulted in a sensitivity of 37.1%, specificity of 81.4%, and accuracy of 61.5%. Conclusions These findings demonstrate significant discordance between the TME of the biopsy and resection specimens. Caution should be used when basing treatment decisions on pre-treatment endoscopic biopsy findings and when interpreting changes in the TME between pre-treatment biopsy and resection specimens after neoadjuvant therapy. Keywords Tumor microenvironment · Tumor infiltrating lymphocytes · Colorectal cancer · Biopsy
Introduction Disclaimers: The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the Department of the Army, the Department of the Air Force, the Department of Defense, or the U.S. Government. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02784-5) contains supplementary material, which is available to authorized users. * Phillip M. Kemp Bohan [email protected] 1
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