The Determination of Immunomodulation and Its Impact on
Survival of Rectal Cancer Patients Depends on the Area
Comprising a Tissue Microarray

J 2020

The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray

GRUBER, E.S.; G. OBERHUBER; D. PILS; T. STORK; K. SINN et al.

Základní údaje

Originální název

The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray

Autoři

GRUBER, E.S.; G. OBERHUBER; D. PILS; T. STORK; K. SINN; S. GRUBER; R. NICA; D. KOLMER; Suzanne Dawn TURNER; M. SCHLEDERER; J. WIDDER; W. DOERR; B. TELEKY a L. KENNER

Vydání

Cancers, BASEL, MDPI, 2020, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.639

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/20:00118357

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

Irradiated rectal cancer; Immunoscore; virtual microscopy; digital pathology; tissue microarray (TMA)

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 3. 2021 19:32, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Background: T cell density in colorectal cancer (CRC) has proven to be of high prognostic importance. Here, we evaluated the influence of a hyperfractionated preoperative short-term radiation protocol (25 Gy) on immune cell density in tumor samples of rectal cancer (RC) patients and on patient survival. In addition, we assessed spatial tumor heterogeneity by comparison of analogue T cell quantification on full tissue sections with digital T cell quantification on a virtually established tissue microarray (TMA). Methods: A total of 75 RC patients (60 irradiated, 15 treatment-naive) were defined for retrospective analysis. RC samples were processed for immunohistochemistry (CD3, CD8, PD-1, PD-L1). Analogue (score 0-3) as well as digital quantification (TMA: 2 cores vs. 6 cores, mean T cell count) of marker expression in 2 areas (central tumor, CT; invasive margin, IM) was performed. Survival was estimated on the basis of analogue as well as digital marker densities calculated from 2 cores (Immunoscore: CD3/CD8 ratio) and 6 cores per tumor area. Results: Irradiated RC samples showed a significant decrease in CD3 and CD8 positive T cells, independent of quantification mode. T cell densities of 6 virtual cores approximated to T cell densities of full tissue sections, independent of individual core density or location. Survival analysis based on full tissue section quantification demonstrated that CD3 and CD8 positive T cells as well as PD-1 positive tumor infiltrating leucocytes (TILs) in the CT and the IM had a significant impact on disease-free survival (DFS) as well as overall survival (OS). In addition, CD3 and CD8 positive T cells as well as PD-1 positive TILs in the IM proved as independent prognostic factors for DFS and OS; in the CT, PD-1 positive TILs predicted DFS and CD3 and CD8 positive T cells as well as PD-1 positive TILs predicted OS. Survival analysis based on virtual TMA showed no impact on DFS or OS. Conclusion: Spatial tumor heterogeneity might result in inadequate quantification of immune marker expression; however, if using a TMA, 6 cores per tumor area and patient sample represent comparable amounts of T cell densities to those quantified on full tissue sections. Consistently, the tissue area used for immune marker quantification represents a crucial factor for the evaluation of prognostic and predictive biomarker potential.

Citovat

GRUBER, E.S.; G. OBERHUBER; D. PILS; T. STORK; K. SINN; S. GRUBER; R. NICA; D. KOLMER; Suzanne Dawn TURNER; M. SCHLEDERER; J. WIDDER; W. DOERR; B. TELEKY a L. KENNER. The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray. Cancers. BASEL: MDPI, 2020, roč. 12, č. 3, s. 563-586. ISSN 2072-6694. Dostupné z: https://doi.org/10.3390/cancers12030563.

@article{1750757,
   author = {Gruber, E.S. and Oberhuber, G. and Pils, D. and Stork, T. and Sinn, K. and Gruber, S. and Nica, R. and Kolmer, D. and Turner, Suzanne Dawn and Schlederer, M. and Widder, J. and Doerr, W. and Teleky, B. and Kenner, L.},
   article_location = {BASEL},
   article_number = {3},
   doi = {https://doi.org/10.3390/cancers12030563},
   keywords = {Irradiated rectal cancer; Immunoscore; virtual microscopy; digital pathology; tissue microarray (TMA)},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray},
   url = {https://www.mdpi.com/2072-6694/12/3/563},
   volume = {12},
   year = {2020}
}

TY  - JOUR
ID  - 1750757
AU  - Gruber, E.S. - Oberhuber, G. - Pils, D. - Stork, T. - Sinn, K. - Gruber, S. - Nica, R. - Kolmer, D. - Turner, Suzanne Dawn - Schlederer, M. - Widder, J. - Doerr, W. - Teleky, B. - Kenner, L.
PY  - 2020
TI  - The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray
JF  - Cancers
VL  - 12
IS  - 3
SP  - 563
EP  - 563
PB  - MDPI
SN  - 20726694
KW  - Irradiated rectal cancer
KW  - Immunoscore
KW  - virtual microscopy
KW  - digital pathology
KW  - tissue microarray (TMA)
UR  - https://www.mdpi.com/2072-6694/12/3/563
N2  - Background: T cell density in colorectal cancer (CRC) has proven to be of high prognostic importance. Here, we evaluated the influence of a hyperfractionated preoperative short-term radiation protocol (25 Gy) on immune cell density in tumor samples of rectal cancer (RC) patients and on patient survival. In addition, we assessed spatial tumor heterogeneity by comparison of analogue T cell quantification on full tissue sections with digital T cell quantification on a virtually established tissue microarray (TMA). Methods: A total of 75 RC patients (60 irradiated, 15 treatment-naive) were defined for retrospective analysis. RC samples were processed for immunohistochemistry (CD3, CD8, PD-1, PD-L1). Analogue (score 0-3) as well as digital quantification (TMA: 2 cores vs. 6 cores, mean T cell count) of marker expression in 2 areas (central tumor, CT; invasive margin, IM) was performed. Survival was estimated on the basis of analogue as well as digital marker densities calculated from 2 cores (Immunoscore: CD3/CD8 ratio) and 6 cores per tumor area. Results: Irradiated RC samples showed a significant decrease in CD3 and CD8 positive T cells, independent of quantification mode. T cell densities of 6 virtual cores approximated to T cell densities of full tissue sections, independent of individual core density or location. Survival analysis based on full tissue section quantification demonstrated that CD3 and CD8 positive T cells as well as PD-1 positive tumor infiltrating leucocytes (TILs) in the CT and the IM had a significant impact on disease-free survival (DFS) as well as overall survival (OS). In addition, CD3 and CD8 positive T cells as well as PD-1 positive TILs in the IM proved as independent prognostic factors for DFS and OS; in the CT, PD-1 positive TILs predicted DFS and CD3 and CD8 positive T cells as well as PD-1 positive TILs predicted OS. Survival analysis based on virtual TMA showed no impact on DFS or OS. Conclusion: Spatial tumor heterogeneity might result in inadequate quantification of immune marker expression; however, if using a TMA, 6 cores per tumor area and patient sample represent comparable amounts of T cell densities to those quantified on full tissue sections. Consistently, the tissue area used for immune marker quantification represents a crucial factor for the evaluation of prognostic and predictive biomarker potential.
ER  -

GRUBER, E.S.; G. OBERHUBER; D. PILS; T. STORK; K. SINN; S. GRUBER; R. NICA; D. KOLMER; Suzanne Dawn TURNER; M. SCHLEDERER; J. WIDDER; W. DOERR; B. TELEKY a L. KENNER. The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray. \textit{Cancers}. BASEL: MDPI, 2020, roč.~12, č.~3, s.~563-586. ISSN~2072-6694. Dostupné z: https://doi.org/10.3390/cancers12030563.

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