title: How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?
abstract: Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control (P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group (P = .009). In the neoadjuvant group, a disagreement pattern of "endoscopic strong operative focal" was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining.
authors.affiliation: The Gastroenterology Department, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Alex
authors.initials: A
authors.lastname: Vilkin
authors.affiliation: The Pathology Department, Hasharon Hospital, Petah Tiqva 49100, Israel.
authors.forename: Marisa
authors.initials: M
authors.lastname: Halpern
authors.affiliation: The Pathology Department, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Morgenstern
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Brazovski
authors.affiliation: The Gastroenterology Department, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Gingold-Belfer
authors.affiliation: The Gastroenterology Department, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Boltin
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Purim
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kundel
authors.affiliation: The Gastroenterology Department, Beilinson Hospital, Petah Tiqva 49100, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Welinsky
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah Tiqva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Brenner
authors.affiliation: The Gastroenterology Department, Beilinson Hospital, Petah Tiqva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Niv
authors.affiliation: The Gastroenterology Department, Beilinson Hospital, Petah Tiqva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: zohar_levi@012.net.il.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Levi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D000251:Adenosine Triphosphatases / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D000368:Aged; D059248:Chemoradiotherapy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000032:analysis* / Q000187:drug effects / Q000528:radiation effects; D009687:Nuclear Proteins / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D015203:Reproducibility of Results
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: Chemoradiation; HNPCC; Immunohistochemical staining; Lynch; Neoadjuvant; Reliability