Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis

Sönke Detlefsen; Tobias Windedal; Frédéric Bibeau; Lærke Valsøe Bruhn; Norman Carr; Martin Graversen; Katharina Markowski; Michael Bau Mortensen; Daniel Neureiter; Christine Sempoux; Wiebke Solass; Malene Theilmann Thinesen; Claus Fristrup

doi:10.1016/j.humpath.2021.12.005

Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis

Hum Pathol. 2022 Feb:120:77-87. doi: 10.1016/j.humpath.2021.12.005. Epub 2021 Dec 24.

Affiliations

¹ Department of Pathology, Odense University Hospital, Odense, 5000, Denmark; Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, 5000, Denmark; Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, 5000, Denmark. Electronic address: sonke.detlefsen@rsyd.dk.
² Department of Pathology, Odense University Hospital, Odense, 5000, Denmark; Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, 5000, Denmark.
³ Pathology Department, CHU de Besançon, 25000, University de Franche-Comté, France.
⁴ Department of Pathology, Odense University Hospital, Odense, 5000, Denmark.
⁵ Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, RG24 9NA, UK.
⁶ Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, 5000, Denmark; Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, 5000, Denmark.
⁷ Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), Salzburg, 5020, Austria.
⁸ Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, 5000, Denmark; Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, 5000, Denmark; Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, 5000, Denmark.
⁹ Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, 1011, Switzerland.
¹⁰ Institute of Pathology and Neuropathology, Eberhard-Karls-University Tuebingen and National Center for Pleura and Peritoneum, University of Tuebingen, 72076, Germany; Institute of Pathology, University of Bern, 3008, Bern, Switzerland.

PMID: 34954136
DOI: 10.1016/j.humpath.2021.12.005

Abstract

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (α) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&E-stained slides only (H&E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (α = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (α = 0.78, 95% CI = 0.73-0.83) than for H&E-PRGS (α = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (α = 0.61, 95% CI = 0.54-0.68) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (α = 0.66, 95% CI = 0.57-0.75) and moderate for H&E-PRGS (α = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters.

Keywords: Immunohistochemistry; Interobserver agreement; Peritoneal Regression Grading Score (PRGS); Peritoneal metastasis; Pressurized intraperitoneal aerosol chemotherapy (PIPAC); Response assessment.

MeSH terms

Humans
Immunohistochemistry
Observer Variation
Peritoneal Neoplasms* / pathology
Peritoneum / pathology