Krishnamurti Uma, Zarineh Alireza, Atem Folefac D, Silverman Jan F
Department of Pathology, Western Pennsylvania Hospital, University of Pittsburgh, USA.
Appl Immunohistochem Mol Morphol. 2011 Jan;19(1):28-32. doi: 10.1097/PAI.0b013e3181e9bb6f.
p53 functions as a tumor suppressor gene and is frequently mutated and inactivated in several human cancers. Some studies have shown p53 overexpression in breast cancer to be an independent prognostic indicator. A subset of breast cancers have chromosome 17 polysomy. Although p53 immunostaining has been found to correlate with chromosome 17 polysomy in nonsmall cell lung carcinomas, head and neck squamous cell carcinomas, and bladder carcinomas, its expression has not been correlated with chromosome 17 polysomy in breast carcinomas. In this study, we compared p53 expression by immunohistochemistry in cases of invasive breast carcinoma showing unamplified chromosome 17 polysomy (P) with cases showing HER2 amplification (A) and with those showing neither amplification nor polysomy (N). There was a significant overexpression of p53 in both cases with HER2 amplification and unamplified polysomy 17 compared with cases with neither amplification nor polysomy (7% of N, 25% of P, and 37% of A group were p53 positive). We have shown in an earlier study that invasive breast carcinoma with unamplified chromosome 17 polysomy is associated with several adverse prognostic indicators including a higher Nottingham score and greater estrogen receptor (ER) negativity with a trend toward the amplified group, in contrast to patients with neither amplification nor polysomy. In this study, we now show that p53 positivity in unamplified 17 polysomy identifies cases that are associated with an even higher Nottingham score and greater hormone receptor negativity that is similar to cases with HER2 amplification.
p53作为一种肿瘤抑制基因,在多种人类癌症中经常发生突变并失活。一些研究表明,p53在乳腺癌中的过表达是一个独立的预后指标。一部分乳腺癌存在17号染色体多体性。尽管在非小细胞肺癌、头颈部鳞状细胞癌和膀胱癌中,已发现p53免疫染色与17号染色体多体性相关,但其表达在乳腺癌中尚未与17号染色体多体性相关联。在本研究中,我们通过免疫组织化学比较了浸润性乳腺癌中显示未扩增的17号染色体多体性(P)的病例、显示HER2扩增(A)的病例以及既无扩增也无多体性(N)的病例中的p53表达。与既无扩增也无多体性的病例相比,HER2扩增和未扩增的17号染色体多体性的病例中p53均有显著过表达(N组7%、P组25%、A组37%的病例p53呈阳性)。我们在早期研究中表明,具有未扩增的17号染色体多体性的浸润性乳腺癌与包括更高的诺丁汉评分和更高的雌激素受体(ER)阴性在内的几个不良预后指标相关,与既无扩增也无多体性的患者相比,有向扩增组发展的趋势。在本研究中,我们现在表明,未扩增的17号染色体多体性中的p53阳性识别出与更高的诺丁汉评分和更高的激素受体阴性相关的病例,这与HER2扩增的病例相似。