{"id":6658,"date":"2021-09-13T21:38:12","date_gmt":"2021-09-13T19:38:12","guid":{"rendered":"https:\/\/meddists.com\/learn\/pre-clinical\/pathology\/gastrointestinal-system\/colorectal-cancer\/"},"modified":"2021-10-11T16:43:57","modified_gmt":"2021-10-11T14:43:57","slug":"colorectal-cancer","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/pre-clinical\/pathology\/gastrointestinal-system\/colorectal-cancer\/","title":{"rendered":"Colorectal cancer"},"content":{"rendered":"\n

There are several types of malignant tumors under this category; the most common one being adenocarcinoma<\/strong>.<\/p>\n\n\n\n

Adenocarcinoma<\/h3>\n<\/span>\n\n\n

Although most colorectal adenomas (polyps) do not develop into adenocarcinomas — most adenocarcinomas develop from adenomas — therefore, they are considered as precursor lesions.<\/p>\n\n\n<\/span>\n

Morphology<\/h4>\n<\/span>\n\n\n
  • Can appear anywhere in the colon
    • In the right colon — appear as polypoid, exophytic masses, rarely causing obstruction<\/strong><\/li>
    • In the left colon — appear as annular lesions resembling a “napkin ring”<\/strong> causing luminal obstruction<\/strong><\/li><\/ul><\/li>
    • Regardless of their growth pattern, adenocarcinomas show ulcerations<\/li><\/ul>\n\n\n<\/span>\n

      Pathogenesis<\/h4>\n<\/span>\n\n\n

      As with other types of cancer, the cause is genetic and epigenetic alterations.<\/p>\n\n\n\n

      The two main genetic pathways<\/strong> that are responsible for the development and progression of colorectal adenocarcinoma are:<\/p>\n\n\n\n

      • APC\/\u03b2-catenin pathway<\/strong>
        • Responsible for the majority of colorectal adenocarcinomas<\/li>
        • APC gene — Adenomatous polyposis coli gene<\/strong>
          • Tumor suppressor gene<\/strong><\/li>
          • Lowers \u03b2-catenin concentration<\/strong><\/li>
          • Mutation of the APC gene will lead to increased levels of \u03b2-catenin, promoting uncontrolled cellular proliferation via WNT signaling<\/li><\/ul><\/li>
          • Tumors originating from this pathway will usually have a pedunculated morphology<\/strong><\/li><\/ul><\/li>
          • Microsatellite instability pathway<\/strong>
            • Associated with defects in DNA mismatch repair (MMR)<\/strong> — most commonly MLH1<\/strong> and MSH2<\/strong><\/li>
            • Leading to an accumulation of mutations in microsatellite repeats — microsatellite instability<\/strong>
              • The mutations can affect pro-apoptotic genes (BAX) and later on proliferation inhibitors (TGF-\u03b2 receptors) and pro-oncogenes (BRAF)<\/li><\/ul><\/li>
              • CpG island hypermethylation phenotype (CIMP)<\/strong>
                • A subset of colon cancers with microsatellite instability where there is no mutation of MLH1\/MSH2, but rather promoter hypermethylation<\/li><\/ul><\/li>
                • Tumors originating from this pathway will usually have a sessile morphology<\/strong>, sometimes mucinous<\/strong>
                  • In mucinous adenocarcinomas, the cells contain high amounts of mucin, and in some cases, seem signet-ring-like<\/li><\/ul><\/li><\/ul><\/li><\/ul>\n\n\n<\/span>\n

                    Adenoma-carcinoma sequence — APC\/\u03b2-catenin pathway<\/strong><\/h4>\n<\/span>\n\n\n
                    1. Germline\/somatic mutations of APC gene — “first hit”<\/li>
                    2. Loss of second copy of APC gene — “second hit”<\/li>
                    3. KRAS mutation (downstream participant of TK pathway) — Pedunculated polyp (adenoma) “stage”<\/li>
                    4. Other affected genes — Adenocarcinoma “stage”
                      1. TP53<\/li>
                      2. SMAD2\/4<\/li>
                      3. Telomerase<\/li>
                      4. Many others<\/li><\/ol><\/li><\/ol>\n\n\n\n

                        The hallmark of the sequence is chromosomal instability<\/strong>.<\/p>\n\n\n<\/span>\n

                        Mismatch repair pathway sequence<\/h4>\n<\/span>\n\n\n
                        1. Germline\/somatic mutations of MLH1\/MSH2 (MMR) genes — “first hit”<\/li>
                        2. Loss of second copy
                          • Mutation or hypermethylation<\/li><\/ul><\/li>
                          • Microsatellite instability — Sessile polyp (adenoma) “stage”<\/li>
                          • Other affected genes — Adenocarcinoma “stage”
                            • TGF-\u03b2 receptor<\/li>
                            • BAX<\/li>
                            • BRAF<\/li>
                            • TOP1<\/li>
                            • Usually, no<\/strong> TP53 and KRAS<\/li><\/ul><\/li><\/ol>\n\n\n<\/span>\n

                              Symptoms<\/h4>\n<\/span>\n\n\n
                              • In case of right colon involvement — Iron deficiency anemia<\/strong>, causing fatigue, mostly in older adults<\/li>
                              • In case of left colon involvement — Colorectal bleeding and regional cramping<\/strong><\/li><\/ul>\n\n\n<\/span>\n

                                Staging<\/h4>\n<\/span>\n\n\n
                                • The two most important factors are the depth of invasion<\/strong>, lymphatic involvement<\/strong>, and metastasis<\/strong><\/li>
                                • Compared to the TMN system we’ve covered before, in colorectal adenocarcinoma, the T (marking tumor size) is replaced with the depth of invasion<\/strong><\/li>
                                • Depth of invasion<\/strong>
                                  • Tumors limited to the mucosa show a very good prognosis (100% 5-year survival rate)<\/li>
                                  • Tumors reaching the submucosa and beyond it show poorer prognosis<\/li><\/ul><\/li>
                                  • Lymphatic involvement<\/strong>
                                    • As with other cancers<\/li><\/ul><\/li>
                                    • Metastasis<\/strong>
                                      • Most often involves the liver (portal system) and lungs
                                        • Rectal adenocarcinomas do not drain to the liver, therefore are an exception of this statement<\/li><\/ul><\/li><\/ul><\/li><\/ul>\n\n\n<\/span>\n

                                          Epidemiology<\/h4>\n<\/span>\n\n\n
                                          • One of the leading causes of malignancy-related deaths<\/li>
                                          • More prevalent in the US, less prevalent in Asia<\/li>
                                          • More common in older adults<\/li><\/ul>\n\n\n<\/span>\n

                                            Risk factors<\/h4>\n<\/span>\n\n\n
                                            • Familial Adenomatous Polyps (FAP)<\/li>
                                            • Western diet<\/li>
                                            • NSAIDs show a protective effect
                                              • Inhibition of COX-2 reduces inflammation and reduces cell turnover<\/li><\/ul><\/li><\/ul>\n<\/span>

                                                Adenocarcinoma<\/h3>

                                                Morphology<\/h4>

                                                Pathogenesis<\/h4>

                                                Adenoma-carcinoma sequence — APC\/\u03b2-catenin pathway<\/strong><\/h4>

                                                Mismatch repair pathway sequence<\/h4>

                                                Symptoms<\/h4>

                                                Staging<\/h4>

                                                Epidemiology<\/h4>

                                                Risk factors<\/h4><\/div>","protected":false},"excerpt":{"rendered":"

                                                There are several types of malignant tumors under this category; the most common one being adenocarcinoma. Adenocarcinoma Although most colorectal adenomas (polyps) do not develop into adenocarcinomas — most adenocarcinomas develop from adenomas — therefore, they are considered as precursor lesions. Morphology Can appear anywhere in the colon In the right colon — appear as […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":404,"menu_order":4,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-6658","page","type-page","status-publish","hentry"],"yoast_head":"\nColorectal cancer – Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/pre-clinical\/pathology\/gastrointestinal-system\/colorectal-cancer\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" 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