Skip to main content
Erschienen in: Virchows Archiv 1/2020

14.11.2019 | Brief Report

PD-L1 expression in gastroesophageal dysplastic lesions

verfasst von: Matteo Fassan, Stefano Brignola, Gianmaria Pennelli, Giulia Alberti, Valentina Angerilli, Alessandra Bressan, Antonio Pellino, Cristiano Lanza, Roberta Salmaso, Sara Lonardi, Salvatore Pucciarelli, Gaya Spolverato, Marco Scarpa, Stefano Realdon, Fabio Farinati, Claudio Luchini, Massimo Rugge, Fotios Loupakis

Erschienen in: Virchows Archiv | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Abstract

Immunotherapy has been recently approved for gastric (GC) and gastroesophageal-junction adenocarcinomas (GEC), and PD-L1 immunohistochemical evaluation represents a promising predictive biomarker in this oncological setting. A series of 125 gastroesophageal dysplastic lesions (52 low-grade, 73 high-grade) was investigated for PD-L1 and DNA mismatch repair proteins status. PD-L1 was positive (combined positive score (CPS) ≥ 1) in 48 (31.0%) dysplastic lesions. A higher prevalence of PD-L1–positive cases was observed among esophageal specimens compared with gastric ones (p = 0.0003), in high-grade and adenocarcinoma samples in comparison with low-grade dysplasia (p < 0.0001), and in lesions with mismatch repair deficiency (p = 0.028). For 30 dysplastic samples, a synchronous matched invasive lesion (GC = 15, GEC = 15) was available and tested for PD-L1 expression; a discordant PD-L1 status was observed in 12/30 (40%) cases. A relatively high prevalence in PD-L1 positivity was observed among gastroesophageal dysplastic lesions and this should be taken into consideration for future therapeutic strategies based on this biomarker.
Literatur
1.
Zurück zum Zitat Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science 359:1350–1355CrossRef Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science 359:1350–1355CrossRef
2.
Zurück zum Zitat Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, Miller R, Riaz N, Douillard JY, Andre F, Scarpa A (2019) ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol In Press. https://doi.org/10.1093/annonc/mdz116 Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, Miller R, Riaz N, Douillard JY, Andre F, Scarpa A (2019) ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol In Press. https://​doi.​org/​10.​1093/​annonc/​mdz116
3.
Zurück zum Zitat Boger C, Behrens HM, Mathiak M, Kruger S, Kalthoff H, Rocken C (2016) PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget 7:24269–24283CrossRef Boger C, Behrens HM, Mathiak M, Kruger S, Kalthoff H, Rocken C (2016) PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget 7:24269–24283CrossRef
4.
Zurück zum Zitat Kawazoe A, Kuwata T, Kuboki Y, Shitara K, Nagatsuma AK, Aizawa M, Yoshino T, Doi T, Ohtsu A, Ochiai A (2017) Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients. Gastric Cancer 20:407–415CrossRef Kawazoe A, Kuwata T, Kuboki Y, Shitara K, Nagatsuma AK, Aizawa M, Yoshino T, Doi T, Ohtsu A, Ochiai A (2017) Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients. Gastric Cancer 20:407–415CrossRef
5.
Zurück zum Zitat Cancer Genome Atlas Research Network (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209CrossRef Cancer Genome Atlas Research Network (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209CrossRef
6.
Zurück zum Zitat Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH (2018) Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol 4:e180013CrossRef Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH (2018) Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol 4:e180013CrossRef
7.
Zurück zum Zitat Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT (2017) Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390:2461–2471CrossRef Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT (2017) Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390:2461–2471CrossRef
8.
Zurück zum Zitat Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, Liu XQ, Sher X, Jung H, Lee M, Lee S, Park SH, Park JO, Park YS, Lim HY, Lee H, Choi M, Talasaz A, Kang PS, Cheng J, Loboda A, Lee J, Kang WK (2018) Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med 24:1449–1458CrossRef Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, Liu XQ, Sher X, Jung H, Lee M, Lee S, Park SH, Park JO, Park YS, Lim HY, Lee H, Choi M, Talasaz A, Kang PS, Cheng J, Loboda A, Lee J, Kang WK (2018) Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med 24:1449–1458CrossRef
9.
Zurück zum Zitat Shitara K, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS, KEYNOTE-061 investigators (2018) Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 392:123–133CrossRef Shitara K, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS, KEYNOTE-061 investigators (2018) Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 392:123–133CrossRef
10.
Zurück zum Zitat Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC (2019) Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer 22:828–837CrossRef Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC (2019) Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer 22:828–837CrossRef
11.
Zurück zum Zitat Rugge M, Genta RM, Di Mario F, El-Omar EM, El-Serag HB, Fassan M, Hunt RH, Kuipers EJ, Malfertheiner P, Sugano K, Graham DY (2017) Gastric cancer as preventable disease. Clin Gastroenterol Hepatol 15:1833–1843CrossRef Rugge M, Genta RM, Di Mario F, El-Omar EM, El-Serag HB, Fassan M, Hunt RH, Kuipers EJ, Malfertheiner P, Sugano K, Graham DY (2017) Gastric cancer as preventable disease. Clin Gastroenterol Hepatol 15:1833–1843CrossRef
12.
Zurück zum Zitat Saraggi D, Fassan M, Bornschein J, Farinati F, Realdon S, Valeri N, Rugge M (2016) From Barrett metaplasia to esophageal adenocarcinoma: the molecular background. Histol Histopathol 31:25–32PubMed Saraggi D, Fassan M, Bornschein J, Farinati F, Realdon S, Valeri N, Rugge M (2016) From Barrett metaplasia to esophageal adenocarcinoma: the molecular background. Histol Histopathol 31:25–32PubMed
13.
Zurück zum Zitat Saraggi D, Galuppini F, Remo A, Urso EDL, Bacchin D, Salmaso R, Lanza C, Bao RQ, Fanelli GN, Guzzardo V, Luchini C, Scarpa M, Farinati F, Fassan M, Rugge M (2017) PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions. Histopathology 71:470–474CrossRef Saraggi D, Galuppini F, Remo A, Urso EDL, Bacchin D, Salmaso R, Lanza C, Bao RQ, Fanelli GN, Guzzardo V, Luchini C, Scarpa M, Farinati F, Fassan M, Rugge M (2017) PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions. Histopathology 71:470–474CrossRef
14.
Zurück zum Zitat Fassan M (2018) Molecular diagnostics in pathology: time for a next-generation pathologist? Arch Pathol Lab Med 142:313–320CrossRef Fassan M (2018) Molecular diagnostics in pathology: time for a next-generation pathologist? Arch Pathol Lab Med 142:313–320CrossRef
15.
Zurück zum Zitat Acosta-Gonzalez G, Ouseph M, Lombardo K, Lu S, Glickman J, Resnick MB (2019) Immune environment in serrated lesions of the colon: intraepithelial lymphocyte density, PD-1, and PD-L1 expression correlate with serrated neoplasia pathway progression. Hum Pathol 83:115–123CrossRef Acosta-Gonzalez G, Ouseph M, Lombardo K, Lu S, Glickman J, Resnick MB (2019) Immune environment in serrated lesions of the colon: intraepithelial lymphocyte density, PD-1, and PD-L1 expression correlate with serrated neoplasia pathway progression. Hum Pathol 83:115–123CrossRef
16.
Zurück zum Zitat Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L (2016) HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol 22:5879–5887CrossRef Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L (2016) HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol 22:5879–5887CrossRef
17.
Zurück zum Zitat Fassan M, Mastracci L, Grillo F, Zagonel V, Bruno S, Battaglia G, Pitto F, Nitti D, Celiento T, Zaninotto G, Fiocca R, Rugge M (2012) Early HER2 dysregulation in gastric and oesophageal carcinogenesis. Histopathology 61:769–776CrossRef Fassan M, Mastracci L, Grillo F, Zagonel V, Bruno S, Battaglia G, Pitto F, Nitti D, Celiento T, Zaninotto G, Fiocca R, Rugge M (2012) Early HER2 dysregulation in gastric and oesophageal carcinogenesis. Histopathology 61:769–776CrossRef
18.
Zurück zum Zitat Holokai L, Chakrabarti J, Broda T, Chang J, Hawkins JA, Sundaram N, Wroblewski LE, Peek RM Jr, Wang J, Helmrath M, Wells JM, Zavros Y (2019) Increased programmed death-ligand 1 is an early epithelial cell response to helicobacter pylori infection. PLoS Pathog 15:e1007468CrossRef Holokai L, Chakrabarti J, Broda T, Chang J, Hawkins JA, Sundaram N, Wroblewski LE, Peek RM Jr, Wang J, Helmrath M, Wells JM, Zavros Y (2019) Increased programmed death-ligand 1 is an early epithelial cell response to helicobacter pylori infection. PLoS Pathog 15:e1007468CrossRef
Metadaten
Titel
PD-L1 expression in gastroesophageal dysplastic lesions
verfasst von
Matteo Fassan
Stefano Brignola
Gianmaria Pennelli
Giulia Alberti
Valentina Angerilli
Alessandra Bressan
Antonio Pellino
Cristiano Lanza
Roberta Salmaso
Sara Lonardi
Salvatore Pucciarelli
Gaya Spolverato
Marco Scarpa
Stefano Realdon
Fabio Farinati
Claudio Luchini
Massimo Rugge
Fotios Loupakis
Publikationsdatum
14.11.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 1/2020
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-019-02693-8

Weitere Artikel der Ausgabe 1/2020

Virchows Archiv 1/2020 Zur Ausgabe

Neu im Fachgebiet Pathologie

Assistierter Suizid durch Infusion von Thiopental

Thiopental Originalie

Als Folge des Urteils des Bundesverfassungsgerichts zur Sterbehilfe im Jahr 2020 wurde in den Jahren 2021–2023 eine Reihe (n = 23) von assistierten Suiziden im Landesinstitut für gerichtliche und soziale Medizin Berlin mit jeweils identischen …

Molekularpathologische Untersuchungen im Wandel der Zeit

Open Access Biomarker Leitthema

Um auch an kleinen Gewebeproben zuverlässige und reproduzierbare Ergebnisse zu gewährleisten ist eine strenge Qualitätskontrolle in jedem Schritt des Arbeitsablaufs erforderlich. Eine nicht ordnungsgemäße Prüfung oder Behandlung des …

Vergleichende Pathologie in der onkologischen Forschung

Pathologie Leitthema

Die vergleichende experimentelle Pathologie („comparative experimental pathology“) ist ein Fachbereich an der Schnittstelle von Human- und Veterinärmedizin. Sie widmet sich der vergleichenden Erforschung von Gemeinsamkeiten und Unterschieden von …

Gastrointestinale Stromatumoren

Open Access GIST CME-Artikel

Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei …