Newer pathologic assessment techniques for colorectal carcinoma.

The pathogenesis of colorectal carcinoma is characterized by progressive genetic abnormalities, which lead to proteomic and cellular changes that determine the cancer malignant phenotype. Phenotypic characteristics seen on histopathologic examination (e.g., tumor stage, histologic grade, and vasoinvasiveness) are essential to planning patient management and should continue to be the major focus of pathologists' efforts. Nonetheless, additional markers that improve the prognostic and predictive power of the pathologic analysis of the primary tumor have been the focus of intense research in recent years. Improved prognostic power may derive from advancements in histopathologic evaluation, more sensitive lymph node staging techniques, and specific molecular analysis methods, such as genetic tests or immunophenotypic profiles. Histopathologic improvements are needed to better standardize histologic grade determination and recognize tumor budding at the invasive front as a marker of aggressive biological behavior and an adverse parameter. Ultrastaging of mesenteric lymph nodes remains a controversial area. Genotypic studies are well developed in the areas of microsatellite instability and chromosome 18q deletion/loss of heterozygosity. Immunophenotypic studies are available in a range of areas including tumor suppressor gene/oncogene expression, proliferation/apoptosis, angiogenesis, and cell adhesion and signaling. Gene expression profiles identified by microarray techniques may help to subtype the large category of microsatellite-stable colorectal carcinoma and define immunophenotypic panels to subclassify tumors into prognostic and therapeutic groups. This brief review discusses the most promising of these approaches and evidence supporting their potential clinical utility.