Serrated lesions of the appendix frequently harbor KRAS mutations and not BRAF mutations indicating a distinctly different serrated neoplastic pathway in the appendix.
Appendiceal serrated polyps often morphologically resemble their colorectal counterparts and most pathologists employ colorectal diagnostic terminology when evaluating appendiceal serrated lesions. We analyzed 132 appendiceal lesions for mutations in the RAS/RAF/MAPK pathway in an attempt to (1) determine the frequency of these mutations in appendiceal serrated lesions and (2) correlate the histopathologic features with molecular alterations. The study group of appendiceal serrated lesions (n = 46) was divided into a non-dysplastic group (28/46, subclassified as 7 hyperplastic polyps and 21 sessile serrated adenoma/polyps (SSA/P) using colorectal diagnostic terminology) and dysplastic group (18/46, subclassified as 9 SSA/Ps with cytological dysplasia, 7 traditional serrated adenomas, and 2 adenomas with prominent serrations). Appendiceal non-serrated dysplastic lesions (n = 86) comprised the control group. Of the 123 lesions analyzed, KRAS mutations were identified in 64 (52%) appendiceal lesions. No significant difference in the presence of KRAS mutations were identified between serrated non-dysplastic lesions (13/25, 52%), serrated dysplastic lesions (7/14, 50%) and the control group of non-serrated dysplastic lesions (44/84, 52%) (P = 1.0). Importantly, KRAS mutations were identified in lesions that were histologically identical to colorectal hyperplastic polyps (2/6, 33%), SSA/Ps (11/19, 58%), and SSA/Ps with cytological dysplasia (4/7, 57%). Of the 126 lesions tested, BRAF V600E mutations were identified in only 5 (4%) appendiceal lesions. Our results indicate that serrated lesions of the appendix often harbor KRAS mutations rather than BRAF mutations and suggest that the serrated pathway in the appendix is likely different than in the colon and rectum.
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Rish K
RK
Pai
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Douglas J
DJ
Hartman
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
David H
DH
Gonzalo
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Keith K
KK
Lai
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Erinn
E
Downs-Kelly
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
John R
JR
Goldblum
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Xiuli
X
Liu
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Deepa T
DT
Patil
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Ana E
AE
Bennett
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Thomas P
TP
Plesec
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Shih-Fan
SF
Kuan
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Marina N
MN
Nikiforova
Department of Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Bonnie
B
Shadrach
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. Electronic address: pair@upmc.edu.
Reetesh K
RK
Pai
D001063:Appendiceal Neoplasms / Q000235:genetics* / Q000473:pathology; D001065:Appendix / Q000473:pathology*; D006801:Humans; D007417:Intestinal Polyps / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
Appendix; BRAF; Hyperplastic polyp; KRAS; Serrated polyp; Sessile serrated adenoma