TY - JOUR
T1 - The prognostic impact of the tumour stroma fraction
T2 - A machine learning-based analysis in 16 human solid tumour types
AU - Micke, Patrick
AU - Strell, Carina
AU - Mattsson, Johanna
AU - Martín-Bernabé, Alfonso
AU - Brunnström, Hans
AU - Huvila, Jutta
AU - Sund, Malin
AU - Wärnberg, Fredrik
AU - Ponten, Fredrik
AU - Glimelius, Bengt
AU - Hrynchyk, Ina
AU - Mauchanski, Siarhei
AU - Khelashvili, Salome
AU - Garcia-Vicién, Gemma
AU - Molleví, David G.
AU - Edqvist, Per Henrik
AU - O´Reilly, Aine
AU - Corvigno, Sara
AU - Dahlstrand, Hanna
AU - Botling, Johan
AU - Segersten, Ulrika
AU - Krzyzanowska, Agnieszka
AU - Bjartell, Anders
AU - Elebro, Jacob
AU - Heby, Margareta
AU - Lundgren, Sebastian
AU - Hedner, Charlotta
AU - Borg, David
AU - Brändstedt, Jenny
AU - Sartor, Hanna
AU - Malmström, Per Uno
AU - Johansson, Martin
AU - Nodin, Björn
AU - Backman, Max
AU - Lindskog, Cecilia
AU - Jirström, Karin
AU - Mezheyeuski, Artur
PY - 2021
Y1 - 2021
N2 - Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed. Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns. Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR(95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59(1.49-8.62)) associations of the tumour stroma fraction with survival. Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance. Funding: The Swedish Cancer Society, The Lions Cancer Foundation Uppsala, The Swedish Government Grant for Clinical Research, The Mrs Berta Kamprad Foundation, Sweden, Sellanders foundation, P.O.Zetterling Foundation, and The Sjöberg Foundation, Sweden.
AB - Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed. Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns. Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR(95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59(1.49-8.62)) associations of the tumour stroma fraction with survival. Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance. Funding: The Swedish Cancer Society, The Lions Cancer Foundation Uppsala, The Swedish Government Grant for Clinical Research, The Mrs Berta Kamprad Foundation, Sweden, Sellanders foundation, P.O.Zetterling Foundation, and The Sjöberg Foundation, Sweden.
U2 - 10.1016/j.ebiom.2021.103269
DO - 10.1016/j.ebiom.2021.103269
M3 - Article
C2 - 33706249
AN - SCOPUS:85102125784
SN - 2352-3964
VL - 65
JO - EBioMedicine
JF - EBioMedicine
M1 - 103269
ER -
