Different apoptotic activity and p21(WAF1/CIP1), but not p27(Kip1), expression in serrated adenomas as compared with traditional adenomas and hyperplastic polyps of the colorectum.
OBJECTIVE
Serrated adenomas (SAs), which include a wide spectrum of lesions, can be broadly divided into two subtypes: type I, closely mimicking hyperplastic polyps (HPs), and type II, unequivocal adenomatous tumor. Our preliminary findings showed clinicopathologic differences between them. The present study was conducted to investigate apoptotic activity and expression of the cell cycle regulator proteins p21(WAF1/CIP1) and p27(Kip1) in type I and II SAs, as compared with traditional adenomas (TAs) and HPs.


METHODS
Apoptotic activity was estimated in hematoxylin-eosin stained specimens, and p21(WAF1/CIP1) or p27(Kip1) immunoreactivity was determined in 62 SAs (19 type I and 43 type II), 50 TAs and 19 HPs. The numbers (percentages) of apoptotic or immunoreactive cells were counted per 1,000 epithelial cells in equally separated crypt zones (upper, middle, and lower thirds).


RESULTS
The apoptotic activity in the middle, but not the upper or lower crypt zone was higher in type II SAs (median 0.2%, interquartile range 0.1-0.5%) than in HPs (0.1%, 0.1-0.2%, P<0.01), whereas it was lower in type I SAs (0.2%, 0.1-0.3%) than in TAs (0.5%, 0.2-0.6%, P<0.001). P21(WAF1/CIP1) expression in the lower crypt zone was higher in both type I and type II SAs (19.8%, 7.0-33.2% and 20.4%, 3.9-47.8%, P<0.0001) than in TAs (1.2%, 0.6-5.2%), and a similar tendency was also observed for the middle crypt zone. p27(Kip1) expression did not vary among the groups.


CONCLUSIONS
The differences in apoptotic activity and p21(WAF1/CIP1) expression between SAs and TAs or HPs indicate that SA should be considered as a distinct subtype of colorectal neoplasm. The two subtypes of SA do not differ in these parameters despite specific clinicopathological features.
Mitomi
Hiroyuki
H
Department of Pathology, National Sagamihara Hospital, 18-1 Sakura-dai, 228-8522, Sagamihara, Kanagawa, Japan. h-mitomi@sagamihara-hosp.gr.jp
Sada
Miwa
M
Kobayashi
Kiyonori
K
Igarashi
Masahiro
M
Mori
Akio
A
Kanazawa
Hideki
H
Nishiyama
Yasuhiko
Y
Ihara
Atsushi
A
Otani
Yoshimasa
Y
D000236:Adenoma / Q000737:chemistry / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000032:analysis*; D003111:Colonic Polyps / Q000737:chemistry / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D025521:Tumor Suppressor Proteins / Q000032:analysis*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27