Abstract
Invasive primary squamous cell carcinomas involving the anorectal region are challenging to manage. Microsatellite instability has been shown to impact clinical courses and outcomes of patients affected by many types of carcinomas. To the best of our knowledge, there are no reports on microsatellite instability in anorectal squamous cell carcinomas. Here, we report a HPV-negative anorectal squamous cell carcinoma which, despite cisplatin-based chemoradiation therapy, showed progression. Interestingly, after identification of its mismatch repair-deficiency (MLH1/PMS2-absent, MSH2/MSH6-intact), pembrolizumab-based immunotherapy was initiated, leading to a marked clinical response. This unique case illustrates that microsatellite instability testing and immunotherapy targeting immune checkpoint blockade should be considered for managing anorectal squamous cell carcinomas that fail conventional chemoradiation therapies or when patients are non-surgical candidates. This report provides the first evidence of microsatellite instability in anorectal squamous cell carcinomas and supports the role for microsatellite instability testing in this cancer type to optimize patient management.
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References
Shia J (2010) An update on tumors of the anal canal. Arch Pathol Lab Med 134(11):1601–1611. https://doi.org/10.1043/2009-0668-RAR.1
Mai S, Welzel G, Ottstadt M, Lohr F, Severa S, Prigge ES, Wentzensen N, Trunk MJ, Wenz F, von Knebel-Doeberitz M, Reuschenbach M (2015) Prognostic relevance of HPV infection and p16 overexpression in squamous cell anal cancer. Int J Radiat Oncol Biol Phys 93(4):819–827. https://doi.org/10.1016/j.ijrobp.2015.08.004
Martin D, Rodel F, Balermpas P, Rodel C, Fokas E (2017) The immune microenvironment and HPV in anal cancer: rationale to complement chemoradiation with immunotherapy. Biochim Biophys Acta 1868(1):221–230. https://doi.org/10.1016/j.bbcan.2017.05.001
Martin D, Balermpas P, Winkelmann R, Rodel F, Rodel C, Fokas E (2018) Anal squamous cell carcinoma - state of the art management and future perspectives. Cancer Treat Rev 65:11–21. https://doi.org/10.1016/j.ctrv.2018.02.001
Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen H-Z, Reeser JW, Yu L, Roychowdhury S (2017) Landscape of microsatellite instability across 39 cancer types. JCO Precision Oncology (1):1–15. https://doi.org/10.1200/po.17.00073
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357(6349):409–413. https://doi.org/10.1126/science.aan6733
Ruemmele P, Dietmaier W, Terracciano L, Tornillo L, Bataille F, Kaiser A, Wuensch PH, Heinmoeller E, Homayounfar K, Luettges J, Kloeppel G, Sessa F, Edmonston TB, Schneider-Stock R, Klinkhammer-Schalke M, Pauer A, Schick S, Hofstaedter F, Baumhoer D, Hartmann A (2009) Histopathologic features and microsatellite instability of cancers of the papilla of vater and their precursor lesions. Am J Surg Pathol 33(5):691–704. https://doi.org/10.1097/PAS.0b013e3181983ef7
Sinicrope FA (2010) DNA mismatch repair and adjuvant chemotherapy in sporadic colon cancer. Nat Rev Clin Oncol 7(3):174–177. https://doi.org/10.1038/nrclinonc.2009.235
Ryan E, Sheahan K, Creavin B, Mohan HM, Winter DC (2017) The current value of determining the mismatch repair status of colorectal cancer: a rationale for routine testing. Crit Rev Oncol Hematol 116:38–57. https://doi.org/10.1016/j.critrevonc.2017.05.006
He EY, Hawkins NJ, Mak G, Roncolato F, Goldstein D, Liauw W, Clingan P, Chin M, Ward RL (2016) The impact of mismatch repair status in colorectal cancer on the decision to treat with adjuvant chemotherapy: an Australian population-based multicenter study. Oncologist 21(5):618–625. https://doi.org/10.1634/theoncologist.2015-0530
Seya T, Tanaka N, Shinji S, Yokoi K, Oguro T, Oaki Y, Ishiwata T, Naito Z, Tajiri T (2007) Squamous cell carcinoma arising from recurrent anal fistula. J Nippon Med Sch 74(4):319–324
Field JK, Kiaris H, Howard P, Vaughan ED, Spandidos DA, Jones AS (1995) Microsatellite instability in squamous cell carcinoma of the head and neck. Br J Cancer 71(5):1065–1069
Tardy MP, Di Mauro I, Ebran N, Refae S, Bozec A, Benezery K, Peyrade F, Guigay J, Sudaka-Bahadoran A, Badoual C, Pedeutour F, Saada-Bouzid E (2018) Microsatellite instability associated with durable complete response to PD-L1 inhibitor in head and neck squamous cell carcinoma. Oral Oncol 80:104–107. https://doi.org/10.1016/j.oraloncology.2018.04.001
Feng YC, Ji WL, Yue N, Huang YC, Ma XM (2018) The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance. Cancer Manag Res 10:105–113. https://doi.org/10.2147/CMAR.S152232
Acknowledgements
We sincerely thank Dr. Bruce Wenig at Moffitt Cancer Center Pathology department for his expertise opinion and suggestions during the preparation of this manuscript.
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Dr. Jiang conceived and designed the study, and wrote, edited, and reviewed the manuscript. Drs. Martens, Meyer, Truong, and Lauwers researched the data and edited and reviewed the manuscript. All authors gave the final approval for publication. Dr. Jiang takes full responsibility for the work, including the study design, access to data, and the decision to submit and publish the manuscript.
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This is a brief report on a novel and unique case of diagnostic interest; it is not a research project; there is no Human or Animal participant(s). Informed consent was acquired although no confidential personal information was cited or disclosed in this brief report.
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Jiang, K., Martens, B., Meyer, L. et al. A mismatch repair-deficient and HPV-negative anorectal squamous cell carcinoma. Virchows Arch 474, 769–773 (2019). https://doi.org/10.1007/s00428-019-02530-y
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DOI: https://doi.org/10.1007/s00428-019-02530-y