Nouman G S, Anderson J J, Crosier S, Shrimankar J, Lunec J, Angus B
Pathology Department, Faculty of Medicine and Medical Science, Umm Alqura University, PO Box 6707, Makkah, Saudi Arabia.
J Clin Pathol. 2003 Jul;56(7):507-11. doi: 10.1136/jcp.56.7.507.
BACKGROUND/AIMS: The inhibitor of growth gene 1 (ING1) is a modulator of cell cycle checkpoints, apoptosis, and cellular senescence. The most widely expressed ING1 isoform is p33(ING1b), which can modulate p53, a molecule that is frequently altered in breast cancer. Reduced ING1 mRNA expression has been observed in primary breast cancer expressing wild-type p53.
p33(ING1b), p53, oestrogen receptor (ER), and progesterone receptor (PgR) expression was studied in 86 primary invasive breast cancers using immunohistochemistry.
Reduced nuclear expression of p33(ING1b) was found in cancer cells, both in intensity and the proportion of cells staining. This was associated with enhanced cytoplasmic p33(ING1b) expression in a proportion of cases. Analysis of several known biological factors indicated that high grade tumours were of larger size and more often negative for ER and PgR expression. However, larger tumours were more frequently p53 negative. These results provide evidence that p33(ING1b) alterations are associated with more poorly differentiated tumours. Positive correlations were found between nuclear p33(ING1b) expression and both ER and PgR expression.
Optimum function of p53 is dependent on p33(ING1b) so that a reduction of nuclear p33(ING1b) expression, as seen in this series, would be predicted to compromise p53 function. This study showed that p33(ING1b) alterations were associated with more poorly differentiated tumours. Therefore, p33(ING1b) expression could be used as a marker of differentiation in invasive breast cancer. These results support the view that loss of p33(ING1b) may be an important molecular event in the differentiation and pathogenesis of invasive breast cancer.
背景/目的：生长抑制基因1（ING1）是细胞周期检查点、细胞凋亡和细胞衰老的调节因子。ING1最广泛表达的异构体是p33（ING1b），它可以调节p53，而p53在乳腺癌中经常发生改变。在表达野生型p53的原发性乳腺癌中观察到ING1 mRNA表达降低。
采用免疫组织化学方法研究了86例原发性浸润性乳腺癌中p33（ING1b）、p53、雌激素受体（ER）和孕激素受体（PgR）的表达。
在癌细胞中发现p33（ING1b）的核表达降低，包括染色强度和染色细胞比例。在一部分病例中，这与细胞质p33（ING1b）表达增强有关。对几种已知生物学因素的分析表明，高级别肿瘤体积更大，ER和PgR表达阴性更为常见。然而，较大的肿瘤更常为p53阴性。这些结果证明p33（ING1b）改变与分化较差的肿瘤有关。核p33（ING1b）表达与ER和PgR表达之间均呈正相关。
p53的最佳功能依赖于p33（ING1b），因此，如本系列研究中所见，核p33（ING1b）表达降低预计会损害p53功能。本研究表明p33（ING1b）改变与分化较差的肿瘤有关。因此，p33（ING1b）表达可作为浸润性乳腺癌分化的标志物。这些结果支持以下观点：p33（ING1b）缺失可能是浸润性乳腺癌分化和发病机制中的一个重要分子事件。
