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.
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.
Kouvaraki
Maria
M
Laboratory of Histology and Embryology, University of Athens School of Medicine, Athens, Greece.
Gorgoulis
Vassilis G
VG
Rassidakis
George Z
GZ
Liodis
Petros
P
Markopoulos
Christos
C
Gogas
John
J
Kittas
Christos
C
D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D015820:Cadherins / Q000032:analysis*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D018275:Carcinoma, Lobular / Q000473:pathology; D002453:Cell Cycle; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology*; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness; D011003:Ploidies; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*
D014408:Biomarkers, Tumor; D015820:Cadherins; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen