Vol 66, No 5 (2016)
Review paper
Published online: 2017-03-29
The pathomorphologist’s role in the era of personalised therapy regarding the case of colorectal tumours
Nowotwory. Journal of Oncology 2016;66(5):386-395.
Abstract
Colorectal cancer is one of the most common epithelial tumours amongst humans. Effective treatment requires a multidisciplinary approach and in some cases target therapy. In order to introduce treatment, both the clinical stage and pathomorphological diagnosis have to be taken into account. An analysis of the microscopic appearance as well as immunohistochemical and molecular tests are the basis of proper diagnosis. Biomarkers for diagnosis of colorectal cancer can be divided into two groups. The first one constitutes diagnostic and prognostic markers which are commonly used by pathologists. They are useful in the recognition of morphological and clinical features of tumours. The second group of biomarkers is used additionally and has predictive value. In an era of personalised therapy, the pathomrothologist’s role is to assess the prognostic and predictive biomarkers, in order to identify patients who will benefit from molecular targeted therapy. In the case of colorectal cancer mutations of genes: KRAS, NRAS and BRAF are clinically significant. A lack of the aforementioned mutations correlates with a better response to anti-EGRF therapy.
Keywords: colorectal cancercarcinogenesis pathwaysprognostic biomarkerspredictive biomarkersCINMSICIMPBRAF mutations
References
- Wojciechowska U, Didkowska J. Nowotwory w Polsce w 2012 roku. Nowotwory. Journal of Oncology. 2013; 63(3): 197–216.
- Kozierkiewicz A, Śliwczyński A, Pakulski M, et al. Wydatki na leczenie raka piersi w Polsce. Nowotwory. Journal of Oncology. 2013; 63(3): 217–226.
- Nasierowska-Guttmejer A. Najczęstsze błędy na linii onkolog – patomorfolog. Onkologia po Dyplomie. 2014; 11: 26–31.
- Nasierowska-Guttmejer A. Zasady postępowania z materiałem operacyjnym u chorych na raka jelita grubego — przygotowanie materiału tkankowego do badania histologicznego. Pol J Pathol. 2014; 65(4 Suppl 1): S37–S39.
- Nasierowska-Guttmejer A. Zasady postępowania z materiałem operacyjnym u chorych na raka jelita grubego — standardowe i wysokospecjalistyczne badania dodatkowe w raku jelita grubego. Pol J Pathol. 2014; 65(4): S40–S50.
- Cree IA, Deans Z, Ligtenberg MJL, et al. European Society of Pathology Task Force on Quality Assurance in Molecular Pathology, Royal College of Pathologists. Guidance for laboratories performing molecular pathology for cancer patients. J Clin Pathol. 2014; 67(11): 923–931.
- van Krieken JH, Jung A, Kirchner T, et al. KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch. 2008; 453(5): 417–431.
- Rosai J. Rosai and Ackerman’s Surgical Pathology. 10th ed. Edinburgh: Mosby Elsewier. ; 2011: 54–55.
- Olsen J, Espersen MLM, Jess P, et al. The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review. Surg Oncol. 2014; 23(3): 167–176.
- Scholl C, Bansal D, Döhner K, et al. The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis. J Clin Invest. 2007; 117(4): 1037–1048.
- Debruyne P, Witek M, Gong Li, et al. Bile Acids Induce Ectopic Expression of Intestinal Guanylyl Cyclase C Through Nuclear Factor-κB and Cdx2 in Human Esophageal Cells. Gastroenterology. 2006; 130(4): 1191–1206.
- Liu Q, Teh M, Ito K, et al. CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer. Mod Pathol. 2007; 20(12): 1286–1297.
- Bressenot A, Cahn V, Danese S, et al. Microscopic features of colorectal neoplasia in inflammatory bowel diseases. World J Gastroenterol. 2014; 20(12): 3164–3172.
- Kołos M, Wasążnik-Jędras A, Nasierowska-Guttmejer A. Can the histological type of colorectal cancer determine the carcinogenesis pathway? Pol J Pathol. 2015; 66(2): 109–120.
- Guzińska-Ustymowicz K, Nasierowska-Guttmejer A. Nowotwory podścieliskowe przewodu pokarmowego. Pol J Pathol. 2013; 64(4 Suppl 2): S47–S54.
- Nasierowska-Guttmejer A. Nowotwory podścieliskowe przewodu pokarmowego (GIST). In: Jeziorski A, Rutkowski P. ed. Mięsaki tkanek miękkich. Via Medica, Gdańsk 2015: 130–134.
- Wrba F, Miettinen M, Lasota J, et al. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol. 2003; 54(1): 3–24.
- Bosman Ft, Yan P, Budinska E, et al. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. J Pathol. 2013; 231(1): 63–76.
- Setaffy L, Langner C. Microsatellite instability in colorectal cancer: clinicopathological significance. Pol J Pathol. 2015; 66(3): 203–218.
- Coppedè F, Lopomo A, Spisni R, et al. Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J Gastroenterol. 2014; 20(4): 943–956.
- Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta. 2003; 1653(1): 1–24.
- Bedeir A, Krasinskas AM. Molecular diagnostics of colorectal cancer. Arch Pathol Lab Med. 2011; 135(5): 578–587.
- Klusek J, Głuszek S. Wybrane mutacje związane z dużym ryzykiem wystąpienia nowotworów jelita grubego. Przegląd Gastroenterol. 2012; 7: 1–6.
- Deptała A. Rak jelita grubego. Termedia Wydawnictwa Medyczne, Poznań 2012.
- Lynch HT, Lanspa SJ, Boman BM, et al. Hereditary nonpolyposis colorectal cancer--Lynch syndromes I and II. Gastroenterol Clin North Am. 1988; 17(4): 679–712.
- Cunningham JM, Christensen ER, Tester DJ, et al. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res. 1998; 58(15): 3455–3460.
- Olszewski WP, Olszewski WT. Rola patomorfologa w doborze terapii ukierunkoweanej na receptor czynnika wzrostu naskórka (EGFR) u chorych na nowotwory. Onkol Prak Klin. 2010; 6: 228–235.
- Berg M, Soreide K. EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways in colorectal cancer: implications for targeted therapy. Discov Med. 2012; 14(76): 207–214.
- Hecht JR, Mitchell E, Neubauer MA, et al. Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer. Clin Cancer Res. 2010; 16(7): 2205–2213.
- Chung KiY, Shia J, Kemeny NE, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005; 23(9): 1803–1810.
- Atkins D, Reiffen KA, Tegtmeier CL, et al. Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem. 2004; 52(7): 893–901.
- National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: colon cancer V2 2015. 2015.
- Dienstmann R, Salazar R, Tabernero J. The evolution of our molecular understanding of colorectal cancer: what we are doing now, what the future holds, and how tumor profiling is just the beginning. Am Soc Clin Oncol Educ Book. 2014: 91–99.
- Domagała P, Kowalik A. Badanie molekularnych markerów wykorzystywanych w leczeniu chorych na raka jelita grubego. Pol J Pathol. 2014; 65(4 Suppl 1): S59–S77.
- Siena S, Sartore-Bianchi A, Di Nicolantonio F, et al. Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst. 2009; 101(19): 1308–1324.
- Clarke CN, Kopetz ES. BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: clinical characteristics, clinical behavior, and response to targeted therapies. J Gastrointest Oncol. 2015; 6(6): 660–667.
- Sinicrope FA, Shi Q, Smyrk TC, et al. Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology. 2015; 148(1): 88–99.
- Capalbo C, Marchetti P, Coppa A, et al. Vemurafenib and panitumumab combination tailored therapy in BRAF-mutated metastatic colorectal cancer: a case report. Cancer Biol Ther. 2014; 15(7): 826–831.
- Tie J, Gibbs P, Lipton L, et al. Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation. Int J Cancer. 2011; 128(9): 2075–2084.
- Richman SD, Seymour MT, Chambers P, et al. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol. 2009; 27(35): 5931–5937.
- Mallinger A, Crumpler S, Pichowicz M, et al. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem. 2015; 58(4): 1717–1735.
- Siedlecki J, Deptała A, Wojtukiewicz MZ. Molekularne czynniki prognostyczne i predykcyjne w raku jelita grubego. In: Rak jelita grubego. Termedia Wydawnictwa Medyczne, Poznań 2012: 34–35.
- Cunningham JM, Kim CY, Christensen ER, et al. The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet. 2001; 69(4): 780–790.
- Vilar E, Scaltriti M, Balmaña J, et al. Microsatellite instability due to hMLH1 deficiency is associated with increased cytotoxicity to irinotecan in human colorectal cancer cell lines. Br J Cancer. 2008; 99(10): 1607–1612.
- Stiegelbauer V, Perakis S, Deutsch A, et al. MicroRNAs as novel predictive biomarkers and therapeutic targets in colorectal cancer. World J Gastroenterol. 2014; 20(33): 11727–11735.
- Cantini L, Isella C, Petti C, et al. MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes. Nat Commun. 2015; 6: 8878.
- Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007; 50(1): 113–130.
- Sadanandam A, Wang X, de Sousa E Melo F, et al. Reconciliation of classification systems defining molecular subtypes of colorectal cancer: interrelationships and clinical implications. Cell Cycle. 2014; 13(3): 353–357.