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Abstract
BackgroundThe 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.MethodsUsing 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.FindingsThe 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.InterpretationOur 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.FundingThe 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.
Highlights
The malignant transformation of cancer cells is accompanied or even preceded by changes in the surrounding stroma [1]
Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer
Our study provides a quantification of the tumour stroma fraction across the major types of solid cancer in human
Summary
The malignant transformation of cancer cells is accompanied or even preceded by changes in the surrounding stroma [1]. The tumour stroma is histologically an integral part of cancer tissue and represents a complex composition of different cell types, including fibroblasts, immune cells and cells of the vasculature, and extracellular matrix [2]. The development of new image analysis systems [13, 14] provides the opportunity to evaluate the tumour stroma in a hitherto unrevealed resolution and accuracy. 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. 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
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