[Aberrant expression and correlative analysis of P16 in breast cancers].
OBJECTIVE
To evaluate the relationship between the aberrant expression of P16 and the clinic-pathological features in breast cancers.


METHODS
In our study, 72 cases of breast cancer were collected and the expressions of P16, HER-2 (human epidermal growth receptor-2), ER (estrogen receptor), PR (progesterone receptor), P53, Ki-67 were measured by immunohistochemistry. The correlations between the P16 and the clinic-pathological features (menstruation, tumor size, histological grade, lymph node metastasis were statistically analyzed.


RESULTS
Aberrant expression of P16 was detected in 36.1%(26/72)of breast cancers. Not only was the staining of P16 increased,but also the subcellular localization was changed from nuclear to cytoplasm or whole cell staining. In general, the occasional cell staining (+) usually presented in nuclear, as expression increased, P16 showed mainly in cytoplasm or whole cells (+++) even diffusive staining in extracellular, and the moderate staining was multi-focal both in nuclear and cytoplasm. The expression of P16 was significantly increased in ER negative group compared with ER positive group (78.6% vs. 9.1%,P=0.000). Statistical analysis showed a significant correlation of high Ki-67 index with the group of P16 positive (Z =-0.263, P=0.003). In addition, significant difference was calculated between pre- and post-menopause (55.6% vs. 24.4%, P=0.008)and P16 expressions were also more credited to the poor-differentiated group in histological grading: 11.8% (2/17) for highly differentiated group, 27.6% (8/29) for moderately differentiated group and 61.5% (16/26) for poorly differentiated group, respectively (P=0.002).


CONCLUSIONS
The aberrant expression of P16 in breast cancers correlated closely with loss of estrogen receptor, high proliferation index or high histological grade, predisposed to the patients of pre-menopause, implicating that the aberrant expression of P16 should be a predictor of poor response to endocrine therapy or more aggressive behavior.
Department of Pathology, Peking University School of Basic Medical Science, Beijing, China.
Su-ping
SP
Cui
Hua-li
HL
Wang
Wei
W
Peng
Hai-jing
HJ
Liu
Lin
L
Hou
Bo
B
Zhang
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C000614131:CDKN2A protein, human