Mutational profiles of different macroscopic subtypes of colorectal adenoma reveal distinct pathogenetic roles for KRAS, BRAF and PIK3CA

BMC Gastroenterology

Ming-Shiang Wu³  Yi-Chia Lee³  Chien-Chuan Chen³  Jaw-Town Lin³  Jin-Tung Liang¹  Chia-Tung Shun²  Han-Mo Chiu³  Li-Chun Chang⁴ 

[1] Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan;Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan;Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

关键词: EGFR;    Non-polypoid colorectal neoplasm;    Gene mutation;   

Others  :  1121718
DOI  :  10.1186/s12876-014-0221-y

 received in 2014-09-11, accepted in 2014-12-12,  发布年份 2014

【 摘 要 】

Background

Investigations 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.

Methods

A 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).

Results

KRAS 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.

Conclusions

Three 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.

【 授权许可】

   
2014 Chang et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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