High Apoptotic Activity and Low Epithelial Cell Proliferation With Underexpression of p21^WAF1/CIP1and p27^Kip1of Mucinous Carcinomas of the Colorectum

Abstract

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.

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

“…The conventional morphologic criteria of apoptotic cells have also been reported to be more reliable (Ansari et al 1993). In addition, our previous study (Akino et al 2002) showed a significant positive correlation between immunohistochemical analysis of single-stranded DNA that detects early-stage apoptosis (Frankfurt et al 1996) and the conventional morphologic assessment that we used here.…”

HATH1 Expression in Mucinous Cancers of the Colorectum and Related Lesions

“…These differences in Wnt signaling may play a role in HATH1 and therefore MUC2 up-regulation in mucinous cancer. Mucinous cancers as a group have been shown to have slower proliferation rates and higher apoptotic indices than nonmucinous cancers (24). Either diminished Wnt signaling and/or HATH1 expression may account for this difference.…”

Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis

“…Compared with non-mucinous CRC, MAC is associated with increased microsatellite instability (MSI) status,8–10 CpG island methylation phenotype,8 9 11 BRAF mutation8 9 and expression of trefoil factor 1 12. On the other hand, MAC is associated with decreased P53 expression,13 14 APC mutation rate8 and p21 expression 15. Conflicting results were reported regarding K-ras mutation rate8 13 and apoptotic activity13 15 in MAC compared with non-mucinous CRC.…”

“…On the other hand, MAC is associated with decreased P53 expression,13 14 APC mutation rate8 and p21 expression 15. Conflicting results were reported regarding K-ras mutation rate8 13 and apoptotic activity13 15 in MAC compared with non-mucinous CRC.…”