Colorectal cancer

Colorectal cancer is the second most common cancer in the industrialized world, accounting for almost two million new cases each year. The main risk factors for its development are obesity, use of alcohol and tobacco, and “western diet” (a diet low in fibers, fruits, vegetables, and consumption of red and processed meat). Up to 8% of colorectal cancer develop as part of inherited syndromes, such as familial adenomatous polyposis coli (FAP), MUTYH-associated polyposis (MAP), or hereditary nonpolypous colorectal cancer (HNPCC; also known as Lynch syndrome). In addition, history of inflammatory bowel diseases (Chron’s disease and ulcerative colitis) represent the third highest risk condition for the development of colorectal cancer.

The main symptoms of colorectal cancer are rectal bleeding, iron-deficiency anemia, abdominal pain, change in bowel habit, and unexplained weight loss. The diagnosis of colorectal cancer is often based on biopsy material obtained through colonoscopy.

The vast majority of colorectal cancer are adenocarcinomas, with less than 10% of the cancers being distinguished by abundant secretion of mucin (mucinous adenocarcinoma). The tumors are classified according to the degree of morphological differentiation into well, moderately, and poorly differentiated. About 80% are well or moderately differentiated with a growth pattern consisting of tumor cells that form irregular glandular structures present at different layers of the bowel wall. Poorly differentiated carcinomas show no, or discrete, glandular formation. Overall poor differentiation with a diffuse infiltrative growth pattern is associated with a poor prognosis. In addition to adenocarcinomas, endocrine tumors can also arise within the colorectal mucosa. Squamous and adenosquamous tumors are exceedingly rare.

Colorectal cancer is considered to develop through a multi-step process, originating from normal colon epithelium that develops into precursor lesions termed adenomas. Adenomas can subsequently further progress into invasive carcinomas with metastatic potential. Spread of colorectal cancer occurs by direct growth through the bowel wall and through invasion of lymphatic and venous channels. The most common sites for metastases are regional lymph nodes and the number of lymph node metastases influences prognosis. The liver is the most common distant site for colorectal cancer metastases.

The TNM classification system of tumor stage is based on the extent of tumor growth into the anatomical layers of the colon and spread outside the colon or into regional lymph nodes. The Dukes classification is an older and less complicated staging system that predates the TNM system and can be translated into new classification system.

Diagnosis of colorectal cancer is based on the microscopical examination of a tumor specimen. Immunohistochemistry can be used to determine a colorectal origin of metastasis or to visualize the spread of tumor cells in surrounding tissues. Antibodies that show high sensitivity and specificity for tumors of colorectal origin include Cytokeratin 20, CDX-2, SATB2, and Cadherin-17. Chromogranin-A antibodies can be used to distinguish endocrine tumors in the bowel from common adenocarcinomas. Immunohistochemical evaluation of microsatellite instability (MSI) in colorectal cancer with antibodies against MSH2, MSH6, MLH1, and PMS1 is used for the screening of Lynch syndrome. Molecular investigation of mutations in KRAS, NRAS, and BRAF genes is used for the selection of patients for different therapy treatments.

The surgical stage at diagnosis is the most important factor for predicting patient outcome, with five-year survival rates of more than 90% for stage I disease and less than 10% for stage IV disease. Patients with mucinous and adenocarcinomas with microsatellite instability have a somewhat better prognosis. Treatment decisions in patients with colorectal cancer are based on the tumor stage and its genetic characteristics, mainly mutations in KRAS and NRAS genes. Epidermal growth factor receptor (EGFR) is commonly expressed in colorectal cancer and monoclonal antibodies inhibiting EGFR demonstrate clinical efficacy in patients with tumors that do not harbor downstream activating RAS mutations.

Colorectal cancer 2, mucinous adenocarcinoma

Female, 69 years, mucinous adenocarcinoma

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Colorectal cancer, mucinous adenocarcinoma

Section of a mucinous colorectal adenocarcinoma, stained with hematoxylin and eosin for contrast.