Auw-Haedrich Claudia, Sundmacher Rainer, Freudenberg Nikolaus, Spelsberg Helga, Feltgen Nicolas, Maier Philip, Reinhard Thomas
Eye Hospital, Albert-Ludwigs-University, 79106 Freiburg, Germany.
Graefes Arch Clin Exp Ophthalmol. 2006 Jan;244(1):96-103. doi: 10.1007/s00417-005-0025-4. Epub 2005 Jul 15.
p63 is a homologue of the tumour suppressor gene p53, which is expressed in human basal squamous epithelium. Some investigators maintain that p63 plays a role in the development of squamous epithelium and, despite its homology to p53, it is considered to act as an oncogene. This study investigated the expression of p63 in conjunctival intraepithelial neoplasia of different grades, and conjunctival squamous cell carcinoma and its correlation to the proliferation marker MIB-1.
Seventeen conjunctival specimens excised with the suspicion of either conjunctival intraepithelial neoplasia (CIN) or squamous cell carcinoma were diagnosed histologically as follows: 2 squamous cell carcinomas of the conjunctiva, 2 CIN grade I, 3 CIN grade II, 7 CIN grade III, 2 CIN with beginning invasion and 1 normal conjunctiva with no dysplasia. Sixteen microscopically-normal postmortem conjunctival specimens and normal conjunctiva, CIN and carcinoma specimens were stained immunohistochemically with antibodies against p63 and MIB-1. At least 500 cells per specimen were counted and the percentage of positively-stained cells of each antibody was calculated.
A mean of 80% (57-89%) of the dysplastic cells from the CIN specimens stained positively with antibodies against p63, especially in the lower two-thirds of the epithelium, statistically significantly more compared with the normal specimens (9-55%, mean 36%, p<0.001). Nevertheless, we did not find a correlation between the percentage of p63-positive cells and the differentiation grade of the malignant specimens. MIB-1 positivity was shown by 0-1% of the cells in the normal postmortem controls, by 3-30% (mean 12%) of the cells in the basal and occasionally in the middle layer of the CIN specimens, and 16-61% (mean 23%) in the carcinoma specimens.
In conjunctival intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva, p63 is preferentially expressed in the immature dysplastic epithelial cells. Its staining does not correlate with MIB-1-expression, and therefore does not appear to be linked to cell proliferation.
p63是肿瘤抑制基因p53的同源物,在人基底鳞状上皮中表达。一些研究者认为p63在鳞状上皮的发育中起作用,尽管它与p53具有同源性,但它被认为是一种癌基因。本研究调查了不同级别结膜上皮内瘤变、结膜鳞状细胞癌中p63的表达及其与增殖标志物MIB-1的相关性。
17例因怀疑结膜上皮内瘤变(CIN)或鳞状细胞癌而切除的结膜标本经组织学诊断如下:2例结膜鳞状细胞癌、2例I级CIN、3例II级CIN、7例III级CIN、2例伴有早期浸润的CIN和1例无发育异常的正常结膜。16例显微镜下正常的尸检结膜标本以及正常结膜、CIN和癌标本用抗p63和MIB-1抗体进行免疫组织化学染色。每个标本至少计数500个细胞,并计算每种抗体阳性染色细胞的百分比。
CIN标本中发育异常细胞平均80%(57 - 89%)对p63抗体呈阳性染色,尤其在上皮的下三分之二,与正常标本(9 - 55%,平均36%)相比有统计学显著差异(p<0.001)。然而,我们未发现p63阳性细胞百分比与恶性标本的分化程度之间存在相关性。在正常尸检对照中,0 - 1%的细胞呈MIB-1阳性,在CIN标本的基底及偶尔的中层中,3 - 30%(平均12%)的细胞呈MIB-1阳性,在癌标本中为16 - 61%(平均23%)。
在结膜上皮内瘤变和结膜鳞状细胞癌中,p63优先在未成熟的发育异常上皮细胞中表达。其染色与MIB-1表达无关,因此似乎与细胞增殖无关。