Abstract
BackgroundInvestigations of genetic alterations and correlations with histology or morphology could provide further insights into colorectal carcinogenesis. Nevertheless, such genetic changes were less investigated in adenoma stage and a comprehensive survey of oncogenic mutations in EGFR signaling pathway according to different morphologic subtypes has not been performed.MethodsA total of 94 neoplasms, including 34 polypoid adenoma, 16 lateral spreading tumors-granular (LST-G), 20 non-granular LST (LST-NG), and 24 depressed tumors, were subjected for mutational analysis of KRAS (exon 2), BRAF (exon 11 and 15), PIK3CA (exon 9 and 20), AKT (exon 4), EGFR (exon 18–24) and HER2 (exon18-24).ResultsKRAS mutation was noted more frequently in LST (13/36, 36.1%) than polypoid neoplasms (5/34, 14.7%, p = 0.041). When comparing with LST-NG, LST-G had a significantly higher frequency of KRAS mutation. (9/16, 56.3% vs. 4/20, 20.0%, p = 0.024). BRAF mutation (V600E) was found in 2 of 36 (5.6%)LSTs and 1 of 34 (2.9%) polypoid lesions. The two LST lesions with BRAF mutation were pathologically proven to be serrated adenoma. PIK3CA mutation (exon 9 E545K) was identified only in LST (5/36, 13.9%). Mutations in KRAS, BRAF or PIK3CA occurred in a mutually exclusive manner. All mutations were absent in the specimens obtained from depressed type neoplasms.ConclusionsThree different macroscopic subtypes of colorectal neoplasms display distinct carcinogenetic pathways in EGFR networking. Further molecular studies of CRCs should take macroscopic subtypes into consideration and highlight the importance of consensus and communication between endoscopic and pathologic diagnosis.
Highlights
Investigations of genetic alterations and correlations with histology or morphology could provide further insights into colorectal carcinogenesis
The classic adenoma-carcinoma sequence of Colorectal cancer (CRC) was defined on histologic grounds and had been the cornerstone of current screening, surveillance and prevention
A substantial portion of CRC was observed to harbor nonoverlapping somatic mutations of KRAS, BRAF, PIK3CA and AKT genes [15,16,17,18,19,20,21,22,23]. Such genetic changes were less investigated in adenoma stage and a comprehensive survey of oncogenic mutations in Epidermal growth factor receptor (EGFR) signaling pathway according to different morphologic subtypes has not been performed
Summary
Investigations of genetic alterations and correlations with histology or morphology could provide further insights into colorectal carcinogenesis Such genetic changes were less investigated in adenoma stage and a comprehensive survey of oncogenic mutations in EGFR signaling pathway according to different morphologic subtypes has not been performed. A better understanding of the molecular mechanisms underlying the development of different CRCs would open the way for patient-specific therapy This is reflected in the current practice that antiepidermal growth factor receptor antibody therapy is no longer offered to CRC patients with mutant KRAS [11]. Elucidation of genetic mechanisms by which these alterations affect colorectal carcinogenesis might have a profound impact on more effective strategies for screening, diagnosis and treatment of CRCs [13,14]
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