Histological Alterations, Diagnosis and Therapeutic Approaches of Colorectal Cancer: A Review Article

Abstract

Colorectal cancer (CRC) is one of the most common cancers and a major public health burden leading to cancer-related morbidity and mortality throughout the world. Its induction is a multistaged process which includes genetic and epigenetic mutations, and complicated environmental/lifestyle interactions. Histologically, CRC is mainly adenocarcinoma that develops from dysplastic transformation of the colonic epithelium and has known variants which affect prognosis and response to treatment. The cumulative effect of architectural distortion, cellular irregularities, invasive extension beyond muscularis mucosae and through the surrounding lymphovascular channels to form metastases describes disease progression. Early diagnosis is paramount for survival. Diagnostic work up includes screening tools, including fecal occult blood test and colonoscopy, followed by histo-pathological diagnosis and radiologic staging. Molecular diagnostics for mutation analysis and microsatellite instabilty status have provided additional clarification to categorization and treatment strategy in recent years. Therapies for CRC are dependent on the stage, as local disease is resected surgically and treatment there-after administered. The introduction of adjuvant and neo-adjuvant systemic chemotherapy, radiotherapy (especially for rectal cancer), new targeted biologic agents, and as of late immune therapy have transformed the management of both metastatic and locally advanced disease. Identification of target therapy according to the molecular tumor profile is essential to patients who respond to this treatment. In conclusion, the histopathological features of CRC and early diagnosis options and modern therapeutic opportunities should be combined to best control colorectal cancer as well as additional new research approaches in response to worldwide diseases.

Keywords:

Cerebrospinal Fluid, Chromosomal Instability, Colorectal Cancer

References

Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood-brain barrier. Neurobiology of disease, 37(1), 13–25. https://doi.org/10.1016/j.nbd.2009.07.030

Adam, R., de Gramont, A., Figueras, J., Kokudo, N., Kunstlinger, F., Loyer, E., Poston, G., Rougier, P., Rubbia-Brandt, L., Sobrero, A., Teh, C., Tejpar, S., Van Cutsem, E., Vauthey, J. N., Pهhlman, L., & of the EGOSLIM (Expert Group on OncoSurgery management of LIver Metastases) group (2015). Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus. Cancer treatment reviews, 41(9), 729–741. https://doi.org/10.1016/j.ctrv.2015.06.006

André, T., Meyerhardt, J., Iveson, T., Sobrero, A., Yoshino, T., Souglakos, J., ... & Shi, Q. (2020). Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): Final results from a prospective, pooled analysis of six randomised, phase 3 trials. The Lancet Oncology, 21(12), 1620–1629. https://doi.org/10.1016/S1470-2045(20)30527-1

Beets-Tan, R. G. H., Lambregts, D. M. J., Maas, M., Bipat, S., Barbaro, B., Curvo-Semedo, L., Fenlon, H. M., Gollub, M. J., Gourtsoyianni, S., Halligan, S., Hoeffel, C., Kim, S. H., Laghi, A., Maier, A., Rafaelsen, S. R., Stoker, J., Taylor, S. A., Torkzad, M. R., & Blomqvist, L. (2018). Magnetic resonance imaging for clinical management of rectal cancer: Updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting. European radiology, 28(4), 1465–1475. https://doi.org/10.1007/s00330-017-5026-2

Blennow, K., & Zetterberg, H. (2018). Biomarkers for Alzheimer's disease: current status and prospects for the future. Journal of internal medicine, 284(6), 643–663. https://doi.org/10.1111/joim.12816

Boland, C. R., & Goel, A. (2010). Microsatellite instability in colorectal cancer. Gastroenterology, 138(6), 2073–2087.e3. https://doi.org/10.1053/j.gastro.2009.12.064

Bosman, F. T., Carneiro, F., Hruban, R. H., & Theise, N. D. (2010). WHO classification of tumours of the digestive system (4th ed.). IARC Press.

Chen, K., Collins, G., Wang, H., & Toh, J. W. T. (2021). Pathological Features and Prognostication in Colorectal Cancer. Current oncology (Toronto, Ont.), 28(6), 5356–5383. https://doi.org/10.3390/curroncol28060447

Dekker, E., Tanis, P. J., Vleugels, J. L. A., Kasi, P. M., & Wallace, M. B. (2019). Colorectal cancer. The Lancet, 394(10207), 1467–1480. https://doi.org/10.1016/S0140-6736(19)32319-0

Fearon E. R. (2011). Molecular genetics of colorectal cancer. Annual review of pathology, 6, 479–507. https://doi.org/10.1146/annurev-pathol-011110-130235

Fenoglio-Preiser, C. M., Noffsinger, A. E., Stemmermann, G. N., Lantz, P. E., & Isaacson, P. G. (2008). Gastrointestinal pathology: An atlas and text (3rd ed.). Lippincott Williams & Wilkins.

Galon, J., Costes, A., Sanchez-Cabo, F., Kirilovsky, A., Mlecnik, B., Lagorce-Pagès, C., Tosolini, M., Camus, M., Berger, A., Wind, P., Zinzindohoué, F., Bruneval, P., Cugnenc, P. H., Trajanoski, Z., Fridman, W. H., & Pagès, F. (2006). Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science (New York, N.Y.), 313(5795), 1960–1964. https://doi.org/10.1126/science.1129139

Heald, R. J., Moran, B. J., Ryall, R. D., Sexton, R., & MacFarlane, J. K. (1998). Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997. Archives of surgery (Chicago, Ill. : 1960), 133(8), 894–899. https://doi.org/10.1001/archsurg.133.8.894

Hugen, N., van de Velde, C. J. H., de Wilt, J. H. W., & Nagtegaal, I. D. (2014). Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Annals of oncology : official journal of the European Society for Medical Oncology, 25(3), 651–657. https://doi.org/10.1093/annonc/mdt591

Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Baron, A., Griffing, S., Holmgren, E., Ferrara, N., Fyfe, G., Rogers, B., Ross, R., & Kabbinavar, F. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. The New England journal of medicine, 350(23), 2335–2342. https://doi.org/10.1056/NEJMoa032691

Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., Nagelhus, E. A., & Nedergaard, M. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science translational medicine, 4(147), 147ra111. https://doi.org/10.1126/scitranslmed.3003748

Imperiale, T. F., Ransohoff, D. F., Itzkowitz, S. H., Levin, T. R., Lavin, P., Lidgard, G. P., Ahlquist, D. A., & Berger, B. M. (2014). Multitarget stool DNA testing for colorectal-cancer screening. The New England journal of medicine, 370(14), 1287–1297. https://doi.org/10.1056/NEJMoa1311194

Jack, C. R., Jr, Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., Sperling, R., … Contributors (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association, 14(4), 535–562. https://doi.org/10.1016/j.jalz.2018.02.018

Kumar, V., Abbas, A. K., & Aster, J. C. (2020). Robbins and Cotran pathologic basis of disease (10th ed.). Elsevier.

Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., Biedrzycki, B., Donehower, R. C., Zaheer, A., Fisher, G. A., Crocenzi, T. S., Lee, J. J., Duffy, S. M., Goldberg, R. M., de la Chapelle, A., Koshiji, M., … Diaz, L. A., Jr (2015). PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. The New England journal of medicine, 372(26), 2509–2520. https://doi.org/10.1056/NEJMoa1500596

Lee, J. K., Liles, E. G., Bent, S., Levin, T. R., & Corley, D. A. (2014). Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Annals of internal medicine, 160(3), 171. https://doi.org/10.7326/M13-1484

Lugli, A., Kirsch, R., Ajioka, Y., Bosman, F., Cathomas, G., Dawson, H., El Zimaity, H., Fléjou, J. F., Hansen, T. P., Hartmann, A., Kakar, S., Langner, C., Nagtegaal, I., Puppa, G., Riddell, R., Ristimنki, A., Sheahan, K., Smyrk, T., Sugihara, K., Terris, B., … Quirke, P. (2017). Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 30(9), 1299–1311. https://doi.org/10.1038/modpathol.2017.46

Misawa, M., & Kudo, S. E. (2025). Current Status of Artificial Intelligence Use in Colonoscopy. Digestion, 106(2), 138–145. https://doi.org/10.1159/000543345

Nagtegaal, I. D., Odze, R. D., Klimstra, D., Paradis, V., Rugge, M., Schirmacher, P., Washington, K. M., Carneiro, F., Cree, I. A., & WHO Classification of Tumours Editorial Board (2020). The 2019 WHO classification of tumours of the digestive system. Histopathology, 76(2), 182–188. https://doi.org/10.1111/his.13975

Pardridge W. M. (2016). CSF, blood-brain barrier, and brain drug delivery. Expert opinion on drug delivery, 13(7), 963–975. https://doi.org/10.1517/17425247.2016.1171315

Rex, D. K., Boland, C. R., Dominitz, J. A., Giardiello, F. M., Johnson, D. A., Kaltenbach, T., … Robertson, D. J. (2017). Colorectal cancer screening: Recommendations for physicians and patients. Gastroenterology, 153(1), 307–323. https://doi.org/10.1053/j.gastro.2017.05.013

Sebag-Montefiore, D., Stephens, R. J., Steele, R., Monson, J., Grieve, R., Khanna, S., Quirke, P., Couture, J., de Metz, C., Myint, A. S., Bessell, E., Griffiths, G., Thompson, L. C., & Parmar, M. (2009). Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet (London, England), 373(9666), 811–820. https://doi.org/10.1016/S0140-6736(09)60484-0

Siravegna, G., Marsoni, S., Siena, S., & Bardelli, A. (2017). Integrating liquid biopsies into the management of cancer. Nature Reviews Clinical Oncology, 14(9), 531–548. https://doi.org/10.1038/nrclinonc.2017.14

Spector, R., & Johanson, C. E. (2007). Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E. Journal of neurochemistry, 103(2), 425–438. https://doi.org/10.1111/j.1471-4159.2007.04773.x

Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D., Aranda Aguilar, E., Bardelli, A., Benson, A., Bodoky, G., Ciardiello, F., D'Hoore, A., Diaz-Rubio, E., Douillard, J. Y., Ducreux, M., Falcone, A., Grothey, A., Gruenberger, T., Haustermans, K., Heinemann, V., … Arnold, D. (2016). ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Annals of oncology : official journal of the European Society for Medical Oncology, 27(8), 1386–1422. https://doi.org/10.1093/annonc/mdw235

Veldkamp, R., Kuhry, E., Hop, W. C., Jeekel, J., Kazemier, G., Bonjer, H. J., Haglind, E., Pهhlman, L., Cuesta, M. A., Msika, S., Morino, M., Lacy, A. M., & COlon cancer Laparoscopic or Open Resection Study Group (COLOR) (2005). Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial. The Lancet. Oncology, 6(7), 477–484. https://doi.org/10.1016/S1470-2045(05)70221-7

WHO Classification of Tumours Editorial Board. (2019). Digestive system tumours (5th ed.). IARC.