Purpose: Identifying rectal cancer patients at risk for local recurrence would allow for refinement in the selection of patients who would benefit from preoperative radiotherapy. PIK3CA, KRAS, and BRAF mutations are commonly found in colon cancers, but their prevalence has not been clearly assessed in rectal cancer. In this study, we aim to determine the mutation frequencies of PIK3CA, KRAS, and BRAF and to investigate whether a mutation may be used as a prognostic parameter in rectal cancer patients. Experimental Design: We evaluated DNA mutations in PIK3CA, KRAS, and BRAF in 240 stage I to III rectal tumors obtained from nonirradiated patients from the Dutch Total Mesorectal Excision trial. Results: PIK3CA, KRAS, and BRAF mutations were identified in 19 (7.9%), 81 (33.9%), and 5 (2.1%) rectal cancers. Patients with PIK3CA mutations developed more local recurrences (5-year risks, 27.8% versus 9.4%; P = 0.006) and tended to develop these recurrences more rapidly after surgery (median local recurrence-free interval since surgery: 7.9 versus 19.6 months; P = 0.07) than patients without PIK3CA mutations. In multivariate analysis, PIK3CA mutations remained as an independent predictor for the development of local recurrences (hazard ratio, 3.4; 95% confidence interval, 1.2-9.2; P = 0.017), next to tumor-node-metastasis stage. Conclusion: PIK3CA mutations can be used as a biomarker in identifying rectal cancer patients with an increased risk for local recurrences. Currently, our findings suggest that prospective evaluation of PIK3CA mutation status could reduce overtreatment by preoperative radiotherapy for the low-risk patients who might otherwise only experience the side effects. (Clin Cancer Res 2009;15(22):6956-62) Colorectal cancer is the third most common cancer and the fourth most frequent cause of cancer deaths worldwide. WHO estimates that 945,000 new cases occur yearly, with 492,000 deaths (1). Approximately 25% of these cases are rectal cancer. In the treatment of rectal cancer patients, local and distant recurrences are a major problem because they are associated with both high morbidity and mortality. The introduction of total mesorectal excision (TME) surgery (2) in combination with preoperative radiotherapy resulted in a reduction of local recurrences (3) and has been recently accepted as standard treatment for rectal cancer in many countries. Although preoperative radiotherapy can prevent local recurrences in certain patients, the majority of patients will not develop a local recurrence without radiotherapy; furthermore, still more than 25% of the patients will develop distant metastases within 5 years of surgery, irrespective of preoperative radiotherapy (3, 4). Moreover, radiotherapy has several substantial negative side effects (5, 6). Therefore, identifying prognostic markers for refinement of personalized treatment is clinically relevant.Recently, Samuels et al. (7) identified somatic mutations in the PIK3CA gene in various human tumors, including colorectal cancer. PIK3CA mutations ha...
Background:Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases.Methods:Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n=39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n=46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n=48).Results:All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified chromosome 20q (P=0.003), significantly fewer mutations in the PI(3)K signalling pathway (P=0.003) and fewer CIMP high tumours (P=0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations.Conclusion:The development of CRC liver metastases is associated with amplification of chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.
<div>Abstract<p><b>Purpose:</b> Identifying rectal cancer patients at risk for local recurrence would allow for refinement in the selection of patients who would benefit from preoperative radiotherapy. <i>PIK3CA, KRAS</i>, and <i>BRAF</i> mutations are commonly found in colon cancers, but their prevalence has not been clearly assessed in rectal cancer. In this study, we aim to determine the mutation frequencies of <i>PIK3CA, KRAS</i>, and <i>BRAF</i> and to investigate whether a mutation may be used as a prognostic parameter in rectal cancer patients.</p><p><b>Experimental Design:</b> We evaluated DNA mutations in <i>PIK3CA, KRAS</i>, and <i>BRAF</i> in 240 stage I to III rectal tumors obtained from nonirradiated patients from the Dutch Total Mesorectal Excision trial.</p><p><b>Results:</b><i>PIK3CA, KRAS</i>, and <i>BRAF</i> mutations were identified in 19 (7.9), 81 (33.9), and 5 (2.1) rectal cancers. Patients with <i>PIK3CA</i> mutations developed more local recurrences (5-year risks, 27.8 versus 9.4; <i>P</i> = 0.006) and tended to develop these recurrences more rapidly after surgery (median local recurrence-free interval since surgery: 7.9 versus 19.6 months; <i>P</i> = 0.07) than patients without <i>PIK3CA</i> mutations. In multivariate analysis, <i>PIK3CA</i> mutations remained as an independent predictor for the development of local recurrences (hazard ratio, 3.4; 95 confidence interval, 1.2-9.2; <i>P</i> = 0.017), next to tumor-node-metastasis stage.</p><p><b>Conclusion:</b><i>PIK3CA</i> mutations can be used as a biomarker in identifying rectal cancer patients with an increased risk for local recurrences. Currently, our findings suggest that prospective evaluation of <i>PIK3CA</i> mutation status could reduce overtreatment by preoperative radiotherapy for the low-risk patients who might otherwise only experience the side effects. (Clin Cancer Res 2009;15(22):695662)</p></div>
<div>Abstract<p><b>Purpose:</b> Identifying rectal cancer patients at risk for local recurrence would allow for refinement in the selection of patients who would benefit from preoperative radiotherapy. <i>PIK3CA, KRAS</i>, and <i>BRAF</i> mutations are commonly found in colon cancers, but their prevalence has not been clearly assessed in rectal cancer. In this study, we aim to determine the mutation frequencies of <i>PIK3CA, KRAS</i>, and <i>BRAF</i> and to investigate whether a mutation may be used as a prognostic parameter in rectal cancer patients.</p><p><b>Experimental Design:</b> We evaluated DNA mutations in <i>PIK3CA, KRAS</i>, and <i>BRAF</i> in 240 stage I to III rectal tumors obtained from nonirradiated patients from the Dutch Total Mesorectal Excision trial.</p><p><b>Results:</b><i>PIK3CA, KRAS</i>, and <i>BRAF</i> mutations were identified in 19 (7.9), 81 (33.9), and 5 (2.1) rectal cancers. Patients with <i>PIK3CA</i> mutations developed more local recurrences (5-year risks, 27.8 versus 9.4; <i>P</i> = 0.006) and tended to develop these recurrences more rapidly after surgery (median local recurrence-free interval since surgery: 7.9 versus 19.6 months; <i>P</i> = 0.07) than patients without <i>PIK3CA</i> mutations. In multivariate analysis, <i>PIK3CA</i> mutations remained as an independent predictor for the development of local recurrences (hazard ratio, 3.4; 95 confidence interval, 1.2-9.2; <i>P</i> = 0.017), next to tumor-node-metastasis stage.</p><p><b>Conclusion:</b><i>PIK3CA</i> mutations can be used as a biomarker in identifying rectal cancer patients with an increased risk for local recurrences. Currently, our findings suggest that prospective evaluation of <i>PIK3CA</i> mutation status could reduce overtreatment by preoperative radiotherapy for the low-risk patients who might otherwise only experience the side effects. (Clin Cancer Res 2009;15(22):695662)</p></div>
Supplementary Data from <i>PIK3CA</i> Mutations Predict Local Recurrences in Rectal Cancer Patients
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.