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.
Highlights
Prognostication of colorectal cancer (CRC) is based on histopathological staging of the resection specimen according to the AJCC/UICC TNM-classification and guides treatment decisions
Several retrospective correlative studies have addressed the prognostic value of the tumor border configuration in early stage CRC (Table 1) and have reported conflicting evidence: in curatively resected submucosally invasive CRC, both Egashira (n = 140) and Wang (n = 159) failed to identify an association of tumor growth pattern with nodal metastasis [32, 35]
Evaluation of the tumor border configuration by the histopathologist identifies distinct subsets of primary CRC (Table 3) and represents an important histomorphological prognostic indicator. It can be assessed on standard H&E slides and is consistently related to survival outcome of patients with transmurally invasive CRC in statistically robust studies and multivariate analysis
Summary
Prognostication of colorectal cancer (CRC) is based on histopathological staging of the resection specimen according to the AJCC/UICC TNM-classification and guides treatment decisions. Even though the TNMclassification is the gold standard in clinical practice, some patients with lower TNM-stages show a worse prognosis compared to patients with a higher tumor stage. This holds true for selected stage I CRC-patients, some of which paradoxically relapse with nodal metastasis after removal of an early invasive lesion [2]. Identification of these patients for segmental resection is of paramount importance for a risk-adapted treatment approach. From the pathologist’s perspective, the recognition, standardization, and reporting of histomorphological prognostic features are an important basis for identification of patient subgroups with a higher risk www.frontiersin.org
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