{"id":487,"date":"2023-06-30T08:35:45","date_gmt":"2023-06-30T06:35:45","guid":{"rendered":"https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/?p=487"},"modified":"2025-10-29T21:38:56","modified_gmt":"2025-10-29T20:38:56","slug":"prognostic-factors-in-colorectal-cancer","status":"publish","type":"post","link":"https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/prognostic-factors-in-colorectal-cancer\/","title":{"rendered":"Prognostic factors in Colorectal Cancer"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">Cancer staging<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The outcome in patients with cancer is determined by a combination of numerous factors. The personalized treatment of a cancer patient depends on the site of origin of the cancer, the morphologic type, and prognostic factors specific to the particular patient and cancer. While this blog post focuses on prognostic factors in colorectal cancer, it&#8217;s helpful to know about the immense influence prognostic factors have on cancer outcome in general (<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/epdf\/10.1002\/ssu.10016\">Gospodarowicz &amp; O\u2019sullivan, 2003<\/a>). According to the <strong>TNM<\/strong> project committee, prognostic factors are classified into three groups. <\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Tumor-related prognostic factors<\/strong> that directly relate to the tumor itself <\/li>\n\n\n\n<li><strong>Host-related prognostic factors<\/strong> include inherent demographic characteristics such as age, gender, race, performance status, comorbidity, and immune status<\/li>\n\n\n\n<li><strong>Environment-related prognostic factors<\/strong> such as choice of treatment, quality of treatment, access to care, or health-care policy (<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/epdf\/10.1002\/ssu.10016\">Gospodarowicz &amp; O\u2019sullivan, 2003<\/a>)<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Colorectal cancer<\/strong> accounts for nearly 1 mio deaths in 2020<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Colorectal cancer<\/strong> (CRC) is one of the most commonly diagnosed cancers worldwide. Although the overall survival has risen due to new treatments and drugs, CRC is still one of the leading causes of cancer-related death (<a href=\"https:\/\/www.frontiersin.org\/journals\/oncology\/articles\/10.3389\/fonc.2019.01284\/full\">Martins et al., 2019<\/a>; <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4223238\/\">Divitiis et al., 2014<\/a>). According to GLOBOCAN data, in 2020, there were an estimated 19.3 million new cases and 10 million cancer deaths worldwide, of which CRC contributed about <strong>1.93 million (10 %) further incidences and 0.94 million (9.4 %) deaths<\/strong> (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8996939\/\">Hossain et al., 2022<\/a>). As early diagnosis of CRC is entirely treatable, accurate determination of tumor-related prognostic factors is of infinite importance.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">TNM classification<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The development of CRC is related to non-modifiable host- and environmental factors, such as age, gender, race, family history, or rare inherited conditions (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8996939\/\">Hossain et al., 2022<\/a>). However, to plan the treatment of an individual CRC patient, tumor-related prognostic factors like growth, invasion, and metastasis are fundamental (<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/epdf\/10.1002\/ssu.10016\">Gospodarowicz &amp; O\u2019sullivan, 2003<\/a>). For this reason, the stage of the cancer is determined via the internationally accepted TNM classification. <\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The <strong>T(umor)<\/strong> category describes the primary tumor site and size, <\/li>\n\n\n\n<li>The <strong>N(node)<\/strong> category describes the regional lymph node involvement <\/li>\n\n\n\n<li>The <strong>M(etastasis)<\/strong> category describes the metastatic spread. <\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1812\" height=\"1305\" src=\"https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2.png\" alt=\"\" class=\"wp-image-512\" srcset=\"https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2.png 1812w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-300x216.png 300w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-1024x737.png 1024w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-768x553.png 768w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-1536x1106.png 1536w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-370x266.png 370w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-270x194.png 270w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-570x411.png 570w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild3-2-740x533.png 740w\" sizes=\"auto, (max-width: 1812px) 100vw, 1812px\" \/><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\"><a href=\"https:\/\/www.cancer.net\/cancer-types\/colorectal-cancer\/stages#tnm-staging\">AJCC Cancer Staging Manual, 8th Edition (2017)<em>, published by Springer International Publishing.<\/em><\/a><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In addition, numbers describe in more detail if and how much cancer is in the body. The earliest stage CRC can have is stage 0, then range from stages I (1) through IV (4). Altogether, combined T, N, and M categories provide detailed information about the stage groups for CRC summarized in the above figure and described in more detail in the following table.<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td>Stage<\/td><td><\/td><\/tr><tr><td>0<\/td><td>&#8220;Cancer in situ&#8221;. The cancer cells are only in the mucosa, or the inner lining, of the<br> colon or rectum.<\/td><\/tr><tr><td>I<\/td><td>The cancer has grown through the mucosa and has invaded the muscular layer of <br>the colon or rectum. It has not spread into nearby tissue or lymph nodes (T1 or T2,<br> N0, M0).<\/td><\/tr><tr><td>IIA<\/td><td>The cancer has grown through the wall of the colon or rectum but has not spread <br>to nearby tissue or to the nearby lymph nodes (T3, N0, M0).<\/td><\/tr><tr><td>IIB<\/td><td>The cancer has grown through the layers of the muscle to the lining of the <br>abdomen, called the visceral peritoneum. It has not spread to the nearby lymph<br> nodes or elsewhere (T4a, N0, M0).<\/td><\/tr><tr><td>IIC<\/td><td>The cancer has spread through the wall of the colon or rectum and has grown into <br>nearby structures. It has not spread to the nearby lymph nodes or elsewhere (T4b, <br>N0, M0).<\/td><\/tr><tr><td>IIIA<\/td><td>The cancer has grown through the inner lining or into the muscle layers of the <br>intestine. It has spread to 1 to 3 lymph nodes or to a nodule of tumor cells in <br>tissues around the colon or rectum that do not appear to be lymph nodes, but has <br>not spread to other parts of the body (T1 or T2, N1 or N1c, M0; or T1, N2a, M0).<\/td><\/tr><tr><td>IIIB<\/td><td>The cancer has grown through the bowel wall or to surrounding organs and into 1 <br>to 3 lymph nodes or to a nodule of tumor in tissues around the colon or rectum <br>that do not appear to be lymph nodes. It has not spread to other parts of the <br>body (T3 or T4a, N1 or N1c, M0; T2 or T3, N2a, M0; or T1 or T2, N2b, M0).<\/td><\/tr><tr><td>IIIC<\/td><td>The cancer of the colon, regardless of how deep it has grown, has spread to 4 or <br>more lymph nodes but not to other distant parts of the body (T4a, N2a, M0; T3 or<br> T4a, N2b, M0; or T4b, N1 or N2, M0).<\/td><\/tr><tr><td>IVA<\/td><td>The cancer has spread to a single distant part of the body, such as the liver or <br>lungs (any T, any N, M1a).<\/td><\/tr><tr><td>IVB<\/td><td>The cancer has spread to more than 1 part of the body (any T, any N, M1b).<\/td><\/tr><tr><td>IVC<\/td><td>The cancer has spread to the peritoneum. It may also have spread to other sites or<br> organs (any T, any N, M1c).<\/td><\/tr><\/tbody><\/table><figcaption class=\"wp-element-caption\"><a href=\"https:\/\/www.cancer.net\/cancer-types\/colorectal-cancer\/stages#tnm-staging\">Overview of CRC stages<\/a><\/figcaption><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\">Biomarkers<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Apart from tumor growth, invasion, and metastasis, biological markers (biomarkers) also reveal significant information about a person\u2019s cancer. <strong>Biomarkers are genes, proteins, or other substances that can be measured in blood, tissue, or other fluids<\/strong> functioning as indicators of pathogenic processes, or pharmacologic responses to a therapeutic intervention. The most common prognostic biomarkers in CRC used for diagnosis, progression, prognosis, and treatment are summarized in the following figure.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"606\" height=\"507\" src=\"https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild5-1.png\" alt=\"\" class=\"wp-image-515\" srcset=\"https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild5-1.png 606w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild5-1-300x251.png 300w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild5-1-370x310.png 370w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild5-1-270x226.png 270w, https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/wp-content\/uploads\/2023\/06\/Bild5-1-570x477.png 570w\" sizes=\"auto, (max-width: 606px) 100vw, 606px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>Biomarker<\/strong><\/td><td><strong>Prevalence<\/strong><\/td><td><strong>Function<\/strong><\/td><td><strong>Mutation<\/strong><\/td><td><strong>Heritability<\/strong><\/td><td><strong>Treatment option<\/strong><\/td><\/tr><tr><td><strong>BRAF<\/strong><\/td><td>10-15 % of patients<\/td><td>Stimulates growth and division of cells<\/td><td>Mutation causes uncontrolled growth of cells, which cannot be <br>turned off<\/td><td>Not hereditary<br>(not a germline mutation) \u2192<br>will not pass from one generation to another.<\/td><td>The BRAF V600E mutation is a prognostic biomarker of aggressive <br>tumor growth. Patients need aggressive treatment with chemotherapy. <br>Patients can receive BRAF inhibitors given together with additional <br>inhibitors as a second or third line therapy<\/td><\/tr><tr><td><strong>KRAS<\/strong><\/td><td>40-45 % of patients<\/td><td>Acts as an&nbsp;\u201con\/off\u201d switch that instructs cells to grow and divide or mature<\/td><td>The KRAS gene is an oncogene \u2192<br>mutations cause normal cells to become cancerous.<\/td><td>Not <br>hereditary<\/td><td>Patients with mutated or unknown KRAS status should receive <br>chemotherapy including FOLFOX, CAPOX, or FOLFIRI with <br>or without bevacizumab. <br>Patients  should not receive EGFR-inhibitors like cetuximab<br> or panitumumab alone or in combination with chemotherapy<\/td><\/tr><tr><td><strong>NRAS<\/strong><\/td><td>5 % of patients<\/td><td>Acts as an \u201con\/off\u201d switch to monitor cell growth, division, and movement<\/td><td>Mutation causes the protein to be locked in the \u201con\u201d position <br>driving constant and uncontrolled cell division<\/td><td>Not <br>hereditary<\/td><td>Patients should receive chemotherapy (some examples are FOLFOX,<br> CAPOX, and FOLFIRI), with or without Bevacizumab<\/td><\/tr><tr><td><strong>HER2<\/strong><\/td><td>3-4 % of patients<\/td><td>Receptor on the surface of almost all the cells in our body. <br>It is responsible for the communication between the cells <br>to promote their growth, division, repair, and survival<\/td><td>Mutation causes overexpression resulting in too many <br>HER2 receptors       \u2192 uncontrolled growth and division of cells<\/td><td>Not <br>hereditary<\/td><td>Treatment with dual-targeted therapy against HER2 \u2192<br>combination of trastuzumab with either pertuzumab <br>or lapatinib alone or with chemotherapy<\/td><\/tr><tr><td><strong>NTRK<\/strong><\/td><td>&lt; 1 % of patients<\/td><td>TRK proteins are receptors mostly found on the surface of cells <br>of the nervous system receiving signals from neighboring <br>neurons to instruct cells to grow and divide<\/td><td>NTRK genes can fuse with other non-related genes producing new<br> NTRK fusion proteins that promote uncontrolled cell growth <br>and division in cancer cells<\/td><td>Not <br>hereditary<\/td><td>Treatment with one of two FDA-approved NTRK inhibitors: <br>larotrectinib or entrectinib<\/td><\/tr><tr><td><strong>MSI-H<\/strong><\/td><td>15 % of patients<\/td><td>Microsatellites (MS) are short repetitive DNA sequences providing <br>instructions for our cells on how to grow, carry out specific activities, <br>divide, or die  \u2192 number of microsatellite repeats has to remain <br>the same in all cells guaranteed by the DNA mismatch repair (MMR) process<\/td><td>cancer cells are &#8220;deficient&#8221; in mismatch repair (MMR)&nbsp; <br>\u2192 tumor cells end up with too many microsatellite DNA repeats<br> \u2192 high microsatellite instability (MSI-H)<\/td><td>Not <br>hereditary<\/td><td>Treatment with immune checkpoint inhibitors <br>(Pembrolizumab and\/or Nivolumab)<\/td><\/tr><tr><td><strong>UGT1A1<\/strong><\/td><td>45 % of African patients<br>&nbsp;<br>31 % of European patients<\/td><td>The protein UDP glucuronosyltransferases is an enzyme <br>that is most active in the liver and converts toxic irinotecan (chemotherapy drug) <br>to a non-toxic form<\/td><td>Patients with a UGT1A1 mutation cannot convert toxic irinotecan\u2019s <br>leading to severe toxicity (especially liver toxicity)<\/td><td>Germline mutation \u2192<br>will pass from one generation to another<\/td><td>Irinotecan is a chemotherapy drug commonly used to treat <br>metastatic CRC \u2192 Patients experience severe toxicity <br>during treatment with FOLFIRI, FOLFIRINOX, or irinotecan alone<\/td><\/tr><tr><td><strong>PIK3CA<\/strong><\/td><td>10-20 % of patients<\/td><td>Protein is part of an enzyme called phosphatidylinositol 3-kinase (PI3K) <br>\u2192 PI3K promotes and regulates cell proliferation, migration or movement, <br>apoptosis and survival<\/td><td>Mutation drives the growth of cells.<\/td><td>Not <br>hereditary<\/td><td>Patients should receive standard chemotherapy such as: <br>FOLFOX, CAPOX, or FOLFIRI with or without bevacizumab<\/td><\/tr><tr><td><strong>DPYD<\/strong><\/td><td>5-18 % of patients<\/td><td>Protein converts toxic fluorouracil-based (chemotherapy drugs <br>used in colorectal cancer treatment) to a non-toxic molecule which <br>can be removed from the body.<\/td><td>Patients with a gene mutation either have a less efficient enzyme <br>or complete&nbsp;loss of the enzyme <br>\u2192 no metabolization of chemotherapy drugs possible<\/td><td>Germline mutation \u2192<br>will pass from one generation to another<\/td><td>Patients cannot metabolize fluoropyrimidine-based chemotherapies <br>(FOLFOX, FOLFIRI, FOLFIRINOX, capecitabine, and TAS-102). <br>Patients with less-efficient enzyme activity  experience severe <br>side effects like neutropenia, diarrhea, and mucositis.<br>Patients with no enzyme activity at all may experience<br>life-threatening complications.<\/td><\/tr><tr><td><strong>PTCH1<\/strong><\/td><td>4-5 % of patients<\/td><td>Tumor suppressor gene that is part of the hedgehog signaling pathway<\/td><td>Mutations cause loss of protein function <br>\u2192 hedgehog signaling pathway leads to cancerous cells <br>and tumor growth.<\/td><td>Not <br>hereditary<\/td><td>No FDA approved therapies targeting PTCH1 mutations to date<\/td><\/tr><\/tbody><\/table><figcaption class=\"wp-element-caption\">CRC biomarkers by the <a href=\"https:\/\/www.ccalliance.org\/colorectal-cancer-information\/biomarkers\">Colorectal Cancer Alliance<\/a><\/figcaption><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\">Digital pathology<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Digital pathology plays a key role in the diagnosis of prognostic factors in oncological diseases. Pathologists have to evaluate a large amount of histological data with steadily growing case numbers. Here, <strong>Artificial Intelligence (AI) <\/strong>offers the possibility to compensate the increasing challenges by supporting the pathologist in their daily routines. For instance, AI could be used to perform repetitive tasks such as the analysis of multiple slides of lymph node biopsies to detect (micro) metastases. In addition, it could already been shown that tumor grading and characterization of an invasive tumor front is more precise and reliable if AI was used. Other works have displayed that even genetic mutations, in particular MSI, can be predicted directly from the HE slide. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The transfer of AI solutions to pathology can enable a reduction in workload as it analyzes more data in less time without producing biases. Our <strong><a href=\"http:\/\/www.mikaia.ai\">MIKAIA<\/a>\u00ae <\/strong>pathology software offers the ideal computational support to address your individual image analysis tasks. Use the preinstalled AI-based apps to view, annotate, process and analyze your single or whole-slide images in brightfield or fluorescence. If you are missing a feature or require an individual analysis services, we will help you to achieve your research goals.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Copyright: Adobe Stock \u2013 stock.adobe.com<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cancer staging The outcome in patients with cancer is determined by a combination of numerous factors. The personalized treatment of a cancer patient depends on the site of origin of the cancer, the morphologic type, and prognostic factors specific to the particular patient and cancer. While this blog post focuses on prognostic factors in colorectal [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":2623,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,35],"tags":[7],"coauthors":[54],"class_list":["post-487","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-digital-pathology","category-life-science","tag-mikaia"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Prognostic factors in Colorectal Cancer - SMART SENSING insights<\/title>\n<meta name=\"description\" content=\"Meta description: Explore crucial prognostic factors for evaluating colorectal Cancer and the role digital pathology plays in the diagnosis.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/websites.fraunhofer.de\/smart-sensing-insights\/prognostic-factors-in-colorectal-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Prognostic factors in Colorectal Cancer - 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