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The tumor border configuration of colorectal cancer as a histomorphological prognostic indicator.

Koelzer VH, Lugli A - Front Oncol (2014)

Bottom Line: The invasive margin is a central feature for prognostication shaped by the complex processes governing tumor-host interaction.This pattern, termed "infiltrative tumor border configuration" has been consistently associated with poor survival outcome and early disease recurrence of CRC-patients.A pushing border is a feature frequently associated with mismatch-repair deficiency and can be used to identify patients for molecular testing.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pathology Division and Translational Research Unit, Institute of Pathology, University of Bern , Bern , Switzerland.

ABSTRACT
Histomorphological features of colorectal cancers (CRC) represent valuable prognostic indicators for clinical decision making. The invasive margin is a central feature for prognostication shaped by the complex processes governing tumor-host interaction. Assessment of the tumor border can be performed on standard paraffin sections and shows promise for integration into the diagnostic routine of gastrointestinal pathology. In aggressive CRC, an extensive dissection of host tissue is seen with loss of a clear tumor-host interface. This pattern, termed "infiltrative tumor border configuration" has been consistently associated with poor survival outcome and early disease recurrence of CRC-patients. In addition, infiltrative tumor growth is frequently associated with presence of adverse clinicopathological features and molecular alterations related to aggressive tumor behavior including BRAFV600 mutation. In contrast, a well-demarcated "pushing" tumor border is seen frequently in CRC-cases with low risk for nodal and distant metastasis. A pushing border is a feature frequently associated with mismatch-repair deficiency and can be used to identify patients for molecular testing. Consequently, assessment of the tumor border configuration as an additional prognostic factor is recommended by the AJCC/UICC to aid the TNM-classification. To promote the assessment of the tumor border configuration in standard practice, consensus criteria on the defining features and method of assessment need to be developed further and tested for inter-observer reproducibility. The development of a standardized quantitative scoring system may lay the basis for verification of the prognostic associations of the tumor growth pattern in multivariate analyses and clinical trials. This article provides a comprehensive review of the diagnostic features, clinicopathological associations, and molecular alterations associated with the tumor border configuration in early stage and advanced CRC.

No MeSH data available.


Related in: MedlinePlus

High power image (40×) of a pan-cytokeratin (brown)/CD8 (red) double stain illustrating dense tumor budding at the tumor invasive front. Tumor buds (arrow heads) are defined as single cells or small clusters of up to five cells ahead of the tumor invasive front. High-grade tumor budding is a feature of aggressive biological behavior in colorectal cancer. Even though tumor budding is more frequently observed in cases with an infiltrative tumor border configuration, this is an independent feature observed at high power and must not be used to define the quality of the tumor border.
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Figure 3: High power image (40×) of a pan-cytokeratin (brown)/CD8 (red) double stain illustrating dense tumor budding at the tumor invasive front. Tumor buds (arrow heads) are defined as single cells or small clusters of up to five cells ahead of the tumor invasive front. High-grade tumor budding is a feature of aggressive biological behavior in colorectal cancer. Even though tumor budding is more frequently observed in cases with an infiltrative tumor border configuration, this is an independent feature observed at high power and must not be used to define the quality of the tumor border.

Mentions: Tumor budding, defined as the presence of single cells or small clusters of up to five cells ahead of the invasive front, is frequently observed as a superimposed pattern in cases with an infiltrative tumor border configuration (Figure 3) (26). However, tumor budding is a separate, independent feature observed at high magnification and must not be used to differentiate infiltrative from pushing tumor growth (9). The presence of tumor budding is an increasingly important histomorphological prognostic factor in CRC (11, 24, 27). Biologically, tumor budding is likely the visible correlate of the process of epithelial mesenchymal transition, during which cancer cells, epithelial by nature, acquire mesenchymal characteristics with capability for migration, stromal lysis, and vascular invasion (28). In early stage CRC, the presence of tumor budding can be indicative of clinical undetectable micrometastases present already at the time of resection of the primary tumor (29). In locally advanced CRC, the presence of tumor budding is an important prognostic indicator for a reduced 5-year survival outcome with elevated risk for disease relapse (27, 30–34). Consequently, tumor budding has been designated a category IIB prognostic factor by the CAP (20).


The tumor border configuration of colorectal cancer as a histomorphological prognostic indicator.

Koelzer VH, Lugli A - Front Oncol (2014)

High power image (40×) of a pan-cytokeratin (brown)/CD8 (red) double stain illustrating dense tumor budding at the tumor invasive front. Tumor buds (arrow heads) are defined as single cells or small clusters of up to five cells ahead of the tumor invasive front. High-grade tumor budding is a feature of aggressive biological behavior in colorectal cancer. Even though tumor budding is more frequently observed in cases with an infiltrative tumor border configuration, this is an independent feature observed at high power and must not be used to define the quality of the tumor border.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927120&req=5

Figure 3: High power image (40×) of a pan-cytokeratin (brown)/CD8 (red) double stain illustrating dense tumor budding at the tumor invasive front. Tumor buds (arrow heads) are defined as single cells or small clusters of up to five cells ahead of the tumor invasive front. High-grade tumor budding is a feature of aggressive biological behavior in colorectal cancer. Even though tumor budding is more frequently observed in cases with an infiltrative tumor border configuration, this is an independent feature observed at high power and must not be used to define the quality of the tumor border.
Mentions: Tumor budding, defined as the presence of single cells or small clusters of up to five cells ahead of the invasive front, is frequently observed as a superimposed pattern in cases with an infiltrative tumor border configuration (Figure 3) (26). However, tumor budding is a separate, independent feature observed at high magnification and must not be used to differentiate infiltrative from pushing tumor growth (9). The presence of tumor budding is an increasingly important histomorphological prognostic factor in CRC (11, 24, 27). Biologically, tumor budding is likely the visible correlate of the process of epithelial mesenchymal transition, during which cancer cells, epithelial by nature, acquire mesenchymal characteristics with capability for migration, stromal lysis, and vascular invasion (28). In early stage CRC, the presence of tumor budding can be indicative of clinical undetectable micrometastases present already at the time of resection of the primary tumor (29). In locally advanced CRC, the presence of tumor budding is an important prognostic indicator for a reduced 5-year survival outcome with elevated risk for disease relapse (27, 30–34). Consequently, tumor budding has been designated a category IIB prognostic factor by the CAP (20).

Bottom Line: The invasive margin is a central feature for prognostication shaped by the complex processes governing tumor-host interaction.This pattern, termed "infiltrative tumor border configuration" has been consistently associated with poor survival outcome and early disease recurrence of CRC-patients.A pushing border is a feature frequently associated with mismatch-repair deficiency and can be used to identify patients for molecular testing.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pathology Division and Translational Research Unit, Institute of Pathology, University of Bern , Bern , Switzerland.

ABSTRACT
Histomorphological features of colorectal cancers (CRC) represent valuable prognostic indicators for clinical decision making. The invasive margin is a central feature for prognostication shaped by the complex processes governing tumor-host interaction. Assessment of the tumor border can be performed on standard paraffin sections and shows promise for integration into the diagnostic routine of gastrointestinal pathology. In aggressive CRC, an extensive dissection of host tissue is seen with loss of a clear tumor-host interface. This pattern, termed "infiltrative tumor border configuration" has been consistently associated with poor survival outcome and early disease recurrence of CRC-patients. In addition, infiltrative tumor growth is frequently associated with presence of adverse clinicopathological features and molecular alterations related to aggressive tumor behavior including BRAFV600 mutation. In contrast, a well-demarcated "pushing" tumor border is seen frequently in CRC-cases with low risk for nodal and distant metastasis. A pushing border is a feature frequently associated with mismatch-repair deficiency and can be used to identify patients for molecular testing. Consequently, assessment of the tumor border configuration as an additional prognostic factor is recommended by the AJCC/UICC to aid the TNM-classification. To promote the assessment of the tumor border configuration in standard practice, consensus criteria on the defining features and method of assessment need to be developed further and tested for inter-observer reproducibility. The development of a standardized quantitative scoring system may lay the basis for verification of the prognostic associations of the tumor growth pattern in multivariate analyses and clinical trials. This article provides a comprehensive review of the diagnostic features, clinicopathological associations, and molecular alterations associated with the tumor border configuration in early stage and advanced CRC.

No MeSH data available.


Related in: MedlinePlus