TY - JOUR
T1 - Cea, epcam, αvβ6 and upar expression in rectal cancer patients with a pathological complete response after neoadjuvant therapy
AU - Linders, Daan
AU - Deken, Marion
AU - van der Valk, Maxime
AU - Tummers, Willemieke
AU - Bhairosingh, Shadhvi
AU - Schaap, Dennis
AU - van Lijnschoten, Gesina
AU - Zonoobi, Elham
AU - Kuppen, Peter
AU - van de Velde, Cornelis
AU - Vahrmeijer, Alexander
AU - Sarasqueta, Arantza Farina
AU - Sier, Cornelis
AU - Hilling, Denise
N1 - Funding Information: for this study was obtained by the Bas Mulder Award granted to DH by the Alpe d?HuZes Foundation and Dutch Cancer Society (grant UL2015-7966), and by the Dutch Cancer Society (grant UL2015-8089). Funding was also obtained from the European Commission under two Marie Sk?odowska-Curie Action awards: H2020-MSCA-RISE-2019 (Project number: 872860-PRISAR2) and H2020-MSCA-ITN-2019 (Project number: 857894-CAST). Funding Information: Funding: Funding for this study was obtained by the Bas Mulder Award granted to DH by the Alpe d’HuZes Foundation and Dutch Cancer Society (grant UL2015-7966), and by the Dutch Cancer Society (grant UL2015-8089). Funding was also obtained from the European Commission under two Marie Skłodowska-Curie Action awards: H2020-MSCA-RISE-2019 (Project number: 872860-PRISAR2) and H2020-MSCA-ITN-2019 (Project number: 857894-CAST). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.
AB - Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.
KW - CEA
KW - Complete response
KW - EpCAM
KW - Fluorescence imaging
KW - Preoperative chemo and radiotherapy
KW - Rectal cancer
KW - Response evaluation
KW - Tumor targeted
KW - UPAR
KW - αvβ6
UR - http://www.scopus.com/inward/record.url?scp=85109025176&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/diagnostics11030516
DO - https://doi.org/10.3390/diagnostics11030516
M3 - Article
C2 - 33799475
SN - 2075-4418
VL - 11
JO - Diagnostics
JF - Diagnostics
IS - 3
M1 - 516
ER -