Peter Stoemmer
Pathologie Augsburg, Germany
Title: Tumorbudding in Colorectal Carcinoma - Difficulties in Graduation and some Solutions
Biography
Biography: Peter Stoemmer
Abstract
Infiltration of tumorcells into the peritumoral tissue is one of the most outstanding features of malignancy and, in small tumors/ early tumorstages probably of eminent prognostic relevance.
In colorectal carcinomas (CRCs), the graduation of the invasive potential is difficult and shows high interobserver variability, leading to several –not very convincing- attempts of standardization as a result of mixing different morphological and biochemical modes of invasion.
We analysed different morphological patterns of invasion in CRCs in respect of morphogenous features and biological consequences: The expression of proliferation markers, cell adhesion molecules adherins, and regulators catenins, and invadopia- associated markers like matrix metalloproteinases vinculin and the perinfiltrative tumorstroma.
Materials and methods:
20 hot spots of tumorbuds in 20 cases of CRCs (400 POIs) were analysed in FFPE, 5 ym
IHC. Analysis of E-Cadherin, N-Cadherin withMoAbs I5626 M0735- DAKO North America, Carpinteria California); Ki-67, CD44 with MoAb ( IS2541 M0753 DAKO Denmark Glostrup) Vinculin (PoAb E18720, Spring Bioscience, California)
Results
Tumorbudding (TB) in CRCs is part of the much more complex phenomenon of epithelial- mesenchymal transformation (EMT/TEM). Morphologically tumorbuds were classified in 4 different type: monocellular and oligocellular , (2) trabecular, (3) tubular, (4) irregular and sheetlike. They show different IHC results:
E-Cadherin expression and membranous ß.catenin are lost in (1) and (2) and diiminished in (3); it is well-expressed in (4)
N-Cadherin and nuclear ß-catenin are ncreased in (1), (2) and (3)
Vinculin and CD 44, markers of invadopodia , appperently do not play a significant role in tumorbudding.
Ki-67, a marker of mitotic ability is highly diminished in (1) – (3) and low in (4).
Conclusion
TB is not a simple phenomenon of tumor- cellpropagation but the result of a complete change of intracellular organisations with shift of cadherins and catenins; these changes apparently block the mitotic activity of invading cells. Invasion by TB is in strict contrast to proliferation.
Devellopment of new therapies should keep in mind, that one can either block proliferation or propagation of malignant tumors.