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A novel tumor‐based epithelial‐to‐mesenchymal transition score that associates with prognosis and metastasis in patients with Stage II/III colorectal cancer
Author(s) -
Roseweir A.K.,
Kong C.Y.,
Park J.H.,
Bennett Lindsay,
Powell A.G.M.T.,
Quinn J.,
van Wyk H.C.,
Horgan P.G.,
McMillan D.C.,
Edwards Joanne,
Roxburgh C.S.
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31739
Subject(s) - colorectal cancer , medicine , oncology , metastasis , epithelial–mesenchymal transition , tumor microenvironment , tumor budding , cancer , stage (stratigraphy) , stroma , tissue microarray , immunohistochemistry , biology , lymph node metastasis , paleontology
It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial–mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15–3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17–6.86, p < 0.001) were associated with decreased cancer‐specific survival. The combined EMT score was also associated with increased tumor budding ( p = 0.046), and systemic inflammation ( p = 0.007), as well as decreased memory T‐cells within the stroma ( p = 0.030) and at the invasive margin ( p = 0.035). Furthermore, the combined EMT score was associated with cancer‐specific survival independent of TNM‐stage (HR 4.12 95% CI 2.30–7.39, p < 0.001). In conclusion , a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade.