Colorectal Carcinoma: Diagnostic, Prognostic, and Molecular Features

Abstract

Surgical resection is the primary treatment modality for colorectal cancer, and the pathologic assessment of the resection specimen provides data that is essential for patient management, including the estimation of postoperative outcome and the rationale for adjuvant therapy. The essential elements of the pathological assessment of colorectal cancer resection specimens include the pathologic determination of TNM stage, tumor type, histologic grade, status of resection margins, and vascular invasion. The prognostic and/or predictive value of these elements, as well as guidelines for their derivation and interpretation, are reviewed in detail. Other tissue-based prognostic factors that are strongly suggested by existing data to have stageindependent prognostic value or to predict response to adjuvant therapy but that have not yet been validated for routine patient care are also reviewed. These include perineural invasion, tumor border configuration, host immune response to tumor, and molecular features such as microsatellite instability or loss of heterozygosity of chromosome 18. The need for high-quality, reproducible pathologic data in the care of the colorectal cancer patient, and the dependence of that data on standardization of all aspects of pathological assessment, is emphasized. In short, colorectal cancer is by far the most common malignancy of the gastrointestinal tract, and it is, without question, a "surgical disease." An estimated 92% of colon cancer patients and 84% of rectal cancer patients undergo surgical resection as the primary modality of treatment; the procedure is most typically performed with curative intent. The appropriateness of adjuvant therapy and the prediction of outcome for the patient are, to a large extent, based on the pathologic assessment of the local disease and other tissue-based prognostic factors in the resection specimen. The problems and controversies associated with the assessment of the colorectal resection specimen, and the current recommendations for their interpretation and reporting, are reviewed. SPORADIC COLORECTAL CANCER: THE BASICS THAT ARE NOT SO BASICThe pathology report of a colorectal cancer resection specimen typically documents the anatomic site of the malignancy, the histologic type, the parameters that determine the local tumor stage, and the histopathologic confirmation of distant metastasis, if applicable. Other reported features include those having additional prognostic (related to likelihood of survival) or predictive (related to likelihood of response to therapy) value, as well as those that may be important for clinicopathologic correlation or quality control (e.g., actual tumor size versus size measurement by imaging techniques). Although basic to pathologic assessment, the definition and interpretation of many of these key features is controversial. The lack of consensus on and standardization of interpretation of these features is the basis of much of the variation in pathologic assessment of colorectal cancers. Variability in assessment, in tu...

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