High apoptotic activity and low epithelial cell proliferation with underexpression of p21(WAF1/CIP1) and p27Kip1 of mucinous carcinomas of the colorectum: comparison with well-differentiated type.
We comparatively assessed 41 mucinous colorectal carcinomas (MUCs) and 620 non-MUC (well-, moderately, and poorly differentiated adenocarcinoma) cases for clinicopathologic findings; and 41 MUCs and 115 randomly selected non-MUCs also were studied for the following: (1) apoptotic activity and Ki-67 immunoreactivity; (2) immunohistochemical expression of p21(WAF1/CIP1), p27Kip1, p53, and bcl-2; and (3) c-Ki-ras mutations. The rates for lymph node involvement and peritoneal dissemination were higher in MUCs than in non-MUCs. Multivariate analysis showed MUCs to have a worse prognosis than well-differentiated adenocarcinomas. The Ki-67 labeling for MUCs was significantly lower than that for non-MUCs, whereas the apoptotic index was significantly higher than for the well-differentiated type. The labeling for p21(WAF1/CIP1) and p27Kip1 was lower in MUCs (2.7% and 35.3%, respectively) than in well-differentiated adenocarcinomas (4.2% and 48.6%, respectively). MUCs can be considered a different tumor from the well-differentiated type, with a poor prognosis owing to frequent lymph node metastasis and peritoneal dissemination, and characterized by high apoptotic and low proliferative activities associated with low p21(WAF1/CIP1) and p27Kip1 expression.
Akino
Fumiyuki
F
Department of Pathology, School of Medicine, Kitasato University, Sagamihara, Japan.
Mitomi
Hiroyuki
H
Nakamura
Takatoshi
T
Ohtani
Yoshimasa
Y
Ichinoe
Masaaki
M
Okayasu
Isao
I
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D015996:Survival Rate
C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D050760:Cyclin-Dependent Kinase Inhibitor p27