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Prognostic value of proliferation, PD-L1 and nuclear size in patients with superior sulcus tumours treated with chemoradiotherapy and surgery
  1. Hans Blaauwgeers1,
  2. Birgit I Lissenberg-Witte2,
  3. Chris Dickhoff3,
  4. Sylvia Duin4,
  5. Erik Thunnissen4
  1. 1 Department of Pathology, OLVG LAB BV, Amsterdam, The Netherlands
  2. 2 Department of Epidemiology and Data Science, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  3. 3 Department of Surgery and Cardiothoracic Surgery, Amsterdam UMC - Cancer Center Amsterdam, Amsterdam, The Netherlands
  4. 4 Department of Pathology, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Hans Blaauwgeers, Department of Pathology, OLVG Locatie Oost, Amsterdam 1090 HM, The Netherlands; hansblaauwgeers@icloud.com

Abstract

Aims The aim of this study was to determine the relationship between proliferative activity, PD-L1 status and nuclear size changes after preoperative chemoradiotherapy (CRT) and the clinical outcome in patients with superior sulcus tumours.

Methods Proliferative activity (MIB-1) and PD-L1 status were estimated by immunohistochemistry in the tumour cells of resection specimen in a series of 33 patients with residual tumour after trimodality therapy for a sulcus superior tumour between 2005 and 2014. A morphometric analysis of both pretreatment and post-treatment tumour materials was also performed. Results were related to disease-free survival and overall survival.

Results Low proliferative activity (<20% MIB-1) was associated with better overall survival: 2-year overall survival of 73% compared with 43% and 25%, respectively, for moderate (MIB-1 20%–50%) and high (MIB-1 >50%) proliferative activity (p=0.016). A negative PD-L1 status (<1% positive tumour cells) was also associated with better overall survival (p=0.021). The mean nuclear size of normal lung tissue pneumocytes was significantly smaller compared with the mean nuclear size of tumour cells of the resection specimens (median difference −38.1; range −115.2 to 16.0; p<0.001). The mean nuclear size of tumour cells did not differ between pretreatment biopsies and resection specimens (median difference −4.6; range −75.2 to 86.7; p=0.14). Nuclear size was not associated with survival (p=0.82).

Conclusions Low proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.

  • lung cancer
  • morphometry
  • proliferating cell nuclear antigen
  • immunohistochemistry

Data availability statement

Data are available upon reasonable request. Data from all scored item and measurements are available, but at a single case level not relevant to (supplementary) include in the manuscript.

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Data availability statement

Data are available upon reasonable request. Data from all scored item and measurements are available, but at a single case level not relevant to (supplementary) include in the manuscript.

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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors All authors have contributed significantly to the manuscript, either to statistical analyses, retrieving clinical data, performing immunohistochemical staining, or writing and rewriting the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.