KRAS Mutant Status May Be Associated with Distant Recurrence in Early-stage Rectal Cancer

Sideris, Michail; Moorhead, Jane; Díaz‐Cano, Salvador; Haji, Amyn; Papagrigoriadis, Savvas

doi:10.21873/anticanres.11454

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…Hence, our findings confirm previous evidence that mutations at codons 12 and 13 (G13D, G12D, and G12V) of the KRAS gene are the most frequent mutations in stage I CRC [ 6 – 8 , 17 , 18 ], while NRAS , BRAF , and PIK3CA mutations are rare in this subgroup of CRC [ 6 – 8 , 17 ].…”

Section: Discussionsupporting

confidence: 91%

“…In this study, we investigated the molecular profile of a cohort of stage I CRCs and assessed its association with patient's prognosis and various clinicopathological variables. While the molecular profile of advanced CRC has been largely investigated to predict response to biological drugs [ 14 – 16 ], the mutational status of early CRC (stage I) has been rarely analyzed [ 6 – 8 , 17 , 18 ] and only in studies including stage I CRCs in heterogeneous cohorts of tumors at different pTNM stages [ 6 – 8 , 17 , 18 ]. Therefore, to the best of our knowledge, this represents the first study focused on the molecular profile of stage I CRC.…”

Section: Discussionmentioning

confidence: 99%

“…The prognostic role of KRAS mutations in stage I CRC was previously investigated in two studies that showed that mutations in this gene are associated with shorter overall survival and recurrence-free survival [ 6 , 18 ], while the specific prognostic role of PIK3CA mutations in stage I CRC had not been analyzed thus far. Our findings showed a significant association between KRAS or PIK3CA mutations and shorter CSS.…”

Section: Discussionmentioning

confidence: 99%

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Clinical Impact and Prognostic Role of KRAS/BRAF/PIK3CA Mutations in Stage I Colorectal Cancer

et al. 2018

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Stage I colorectal carcinoma has excellent prognosis, with 5-year survival rate up to 95%. The occurrence of lymphovascular invasion, tumor budding, high number of PDC, or lymph node micrometastases is associated with tumor progression. The aim of this study was to evaluate the mutational status of 62 stage I colorectal carcinomas (CRC) (taken from 37 patients surviving more than five years since the initial diagnosis and from 25 patients who died of disease) and to correlate it with histopathological features and the clinical outcome. Mutations of KRAS, NRAS, BRAF, and PIK3CA genes were analyzed through Myriapod Colon Status Kit, using the high-throughput genotyping platform Sequenom MassARRAY System. Mutations in those genes were found in 31 cases (50%) and mainly in those with poor prognosis. The most frequent mutations occurred at codons 12 and 13 of the KRAS gene (40% of cases). We found concomitant PIK3CA mutations in 5 cases (8%). The presence of PIK3CA mutations was mainly observed in tumors with poor prognosis and with unfavorable histopathological prognostic features. High PDC grade (P = 0.0112), the presence of tumor budding (P = 0.0334), LVI (P < 0.0001), KRAS mutations (P = 0.0228), PIK3CA mutations (P = 0.0214), multiple genetic mutations in KRAS and PIK3CA genes (P = 0.039), and nodal micrometastases (P < 0.0001) were significant prognostic variables for CSS. The presence of LVI was the only independent and statistically significant prognostic variable for CSS in our cohort of pTNM stage I CRCs. The analysis of KRAS/PIK3CA mutational status may be used to identify patients with stage I CRC at high risk of bad outcome and who may need additional treatments, including biological therapies.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Clinical Impact and Prognostic Role of KRAS/BRAF/PIK3CA Mutations in Stage I Colorectal Cancer

et al. 2018

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“…Xiong et al ( 65 ) noticed that the KRAS status in the neoplastic lesion presented on the surface of the endometrium was different from that in the benign metaplastic areas, while Van der Putten et al ( 66 ) found that KRAS mutation appeared both in the hyperplastic lesions and the adjacent benign endometrial tissues. Other studies ( 46 , 62 ) also supported that KRAS mutation occurred in the early stages of type I EC (endometrioid) before clonal expansion, which is similar to the role of KRAS mutation in colorectal cancer ( 67 , 68 ). Endometrial atypical hyperplasia (EAH) is now believed to be the precancerous lesion of EEC, in which KRAS was also a highly mutated gene ( 63 , 64 , 69 ).…”

Section: Kras Mutations In Ec and Its Potential Value In The Fertility-spared Treatmentmentioning

confidence: 55%

The Advance and Correlation of KRAS Mutation With the Fertility-Preservation Treatment of Endometrial Cancer in the Background of Molecular Classification Application

Yu¹,

Wang²

2021

Pathol. Oncol. Res.

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The annually increasing incidence of endometrial cancer in younger women has created a growing demand for fertility preservation. However, the diverse therapeutic efficacy among patients under the same histological subtype and the same tumor grade suggests the potential interference of the innate molecular characteristics. The molecular classification has now been applied in clinical practice and might help to stratify the endometrial cancer patients and individualize the therapy, but the candidates for the fertility-spared treatment are most likely to be subdivided in the subgroup lacking the specific signature. KRAS mutation has been linked to the malignant transition of the endometrium, while its role in molecular classification and fertility preservation is vague. Here, we mainly review the advance of molecular classification and the role of KRAS in endometrial cancer, as well as their correlation with fertility-preservation treatment.

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“…However, the role of MGMT promoter methylation status as an early biomarker of colorectal cancer has not yet been established, despite several studies in colorectal adenoma and adenocarcinoma (14,15). In fact, Sideris et al (16) showed recently that there was no association between the status of MGMT expression and pathological features, including response to neo-adjuvant therapy. Future research will be needed to elucidate the relationship between these biomarkers and rectal cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

MGMT Promoter Methylation in Patients with Rectal Adenocarcinoma After Chemoradiotherapy Treatment: Clinical Implications

et al. 2019

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Aims: To analyze the clinical relevance of O6-methylguanine-DNA methyltransferase in rectal adenocarcinoma treated with chemoradiotherapy followed by surgery. Methods: Tissue samples from 29 rectal adenocarcinoma patients were obtained after chemoradiotherapy. O6-methylguanine-DNA methyltransferase promoter methylation status was established by methylation-specific polymerase chain reaction. O6-methylguanine-DNA methyltransferase protein levels were determined by immunohistochemistry. Clinicopathologic variables, including treatment regression grade, recurrence, lymph node invasion, and stage and differentiation grade of the tumor, were determined. Results: The O6-methylguanine-DNA methyltransferase gene promoter was methylated in 81.5% of samples. Most patients (88.9%) showed low O6-methylguanine-DNA methyltransferase protein expression. O6-methylguanine-DNA methyltransferase methylation status was not correlated with any of the clinicopathological variables determined in rectal adenocarcinomas selected for chemoradiotherapy. Conclusion: O6-methylguanine-DNA methyltransferase methylation status is not correlated with clinicopathologic variables examined in rectal adenocarcinoma selected for chemoradiotherapy, although its role as a biomarker awaits further investigation.

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KRAS Mutant Status May Be Associated with Distant Recurrence in Early-stage Rectal Cancer

Abstract: Abstract. Background

Cited by 11 publications

References 33 publications

Clinical Impact and Prognostic Role of KRAS/BRAF/PIK3CA Mutations in Stage I Colorectal Cancer

Clinical Impact and Prognostic Role of KRAS/BRAF/PIK3CA Mutations in Stage I Colorectal Cancer

The Advance and Correlation of KRAS Mutation With the Fertility-Preservation Treatment of Endometrial Cancer in the Background of Molecular Classification Application

MGMT Promoter Methylation in Patients with Rectal Adenocarcinoma After Chemoradiotherapy Treatment: Clinical Implications

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