RGD Reference Report - High expression levels of p27 correlate with lymph node status in a subset of advanced invasive breast carcinomas: relation to E-cadherin alterations, proliferative activity, and ploidy of the tumors.

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High expression levels of p27 correlate with lymph node status in a subset of advanced invasive breast carcinomas: relation to E-cadherin alterations, proliferative activity, and ploidy of the tumors.
Authors:	Kouvaraki, M Gorgoulis, VG Rassidakis, GZ Liodis, P Markopoulos, C Gogas, J Kittas, C
Citation:	Kouvaraki M, etal., Cancer. 2002 May 1;94(9):2454-65.
RGD ID:	2293607
Pubmed:	PMID:12015771 (View Abstract at PubMed)
DOI:	DOI:10.1002/cncr.10505 (Journal Full-text)
BACKGROUND: The cyclin-dependent kinase inhibitor p27 plays a central role in cell cycle progression and is deregulated in breast carcinomas. Although its levels are inversely associated with tumor proliferation, overexpression of p27 has been reported in a subset of rapidly proliferating breast carcinoma cell lines. METHODS: p27 levels were determined by immunohistochemistry in a series of 52 sporadic invasive breast carcinomas consisting of 47 ductal, 2 lobular, and 3 mixed; most tumors were Grade 2 or 3 (46 of 52) and Tumor Node Metastasis (TNM) Stage II-IV (46 of 52). E-cadherin expression and its gene alterations at 16q22.1 were also studied, because in vitro evidence suggests a biologic association between p27 and E-cadherin-mediated growth suppression. RESULTS: The mean p27 labeling index (LI; percentage of p27 positive tumor cells) was 33.3% +/- 25.3% (range, 0.1-85%). High p27 levels (p27 LI, > 50%) were observed in 14 (26.9%) of 52 carcinomas and were significantly associated with metastatic disease in axillary lymph nodes (14 of 33 vs. 0 of 19; P = 0.0007 by Fisher exact test). In addition, p27 LI was higher in the group of lymph node positive vs. lymph node negative tumors (mean p27 LI, 40.9% vs. 20.1%; P = 0.008 by Mann-Whitney test). Reduced or absent E-cadherin expression was found in 27 of 45 (60%) informative cases. Allelic imbalance of the 16q22.1 locus was found in 14 (27.5%) of 51 cases by using the microsatellite markers D16S503, D16S752, and D16S512. p27 LI and E-cadherin alterations were not statistically related. CONCLUSIONS: In summary, high p27 levels detected in a subset of advanced breast carcinomas correlate with lymph node metastasis, suggesting that other mechanisms may bypass the cell cycle inhibitory role of p27 and provide growth advantage in these tumors.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Lymphatic Metastasis		IEP		2293607	associated with Breast Neoplasms	RGD
Lymphatic Metastasis		ISO	CDKN1B (Homo sapiens)	2293607; 2293607	associated with Breast Neoplasms	RGD

Objects Annotated

Genes (Rattus norvegicus)

Cdkn1b (cyclin-dependent kinase inhibitor 1B)

Genes (Mus musculus)

Cdkn1b (cyclin dependent kinase inhibitor 1B)

Genes (Homo sapiens)

CDKN1B (cyclin dependent kinase inhibitor 1B)

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High expression levels of p27 correlate with lymph node status in a subset of advanced invasive breast carcinomas: relation to E-cadherin alterations, proliferative activity, and ploidy of the tumors.