Basic-alimentary tractA Transient, EMT-Linked Loss of Basement Membranes Indicates Metastasis and Poor Survival in Colorectal Cancer
Section snippets
Tissue Specimens, Patient Data, and Statistics
Formalin-fixed, paraffin-embedded colorectal adenocarcinomas and corresponding metastases from patients who underwent surgery without additional treatments were retrieved from the archives of the Department of Pathology, University of Erlangen-Nürnberg. For clinical correlation with metachronous distant metastasis and survival, we used a collection of 125 pT3 M0 R0 rectal carcinomas with long-time clinical follow-up (patients’ and tumor characteristics are shown in Table 1). The Kaplan–Meier
Selective Loss of the BM at the Invasive Front Associated With EMT
Loss of the BM is generally thought to be an important hallmark for the transition from benign to malignant tumor growth. However, when analyzing colorectal adenocarcinomas, we found that all well- to moderately differentiated tumors expressed BMs (Figure 1), which is in line with previous observations in differentiated types of gastrointestinal cancers.2 BMs, detected by staining of Lama3, surrounded tubular differentiated tumor glands built up by polarized tumor cells in the main tumor mass (
Discussion
Loss of the BM is considered an important step toward tumor invasion and metastasis. The data presented here show new aspects in BM turnover in colorectal carcinomas with impact on malignant tumor progression: (1) The BM is still expressed in the main tumor mass of most colorectal adenocarcinomas but selectively lost at the invasive front in many cases. This loss is not only due to proteolytic breakdown but to a down-regulated synthesis. (2) Selective loss of the BM at the invasive front has
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Supported by grants from the DFG (BR 1399/4-3; to T.B. and T.K.), the Deutsche Krebshilfe (10-2029 Br I; to T.B.); and the BMBF (NGFN2 project No. 01GS0436; to T.B. and T.K.).
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S.S. and O.S. contributed equally to this paper.