Lee C S, Gad J
Department of Anatomical Pathology, The Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Pathol Int. 1998 Oct;48(10):806-11. doi: 10.1111/j.1440-1827.1998.tb03841.x.
Differences in the immunohistochemical expression of the 17 kDa protein encoded by the human nm23-H1 gene were studied in premalignant lesions and invasive squamous cell carcinoma (SCC) (N = 8) of the cervix using routine streptavidin-biotin immunohistochemistry and a polyclonal antibody to the nm23-H1 protein. The premalignant lesions were koilocytic atypia due to wart virus infection (N = 5), low-grade cervical intraepithelial neoplasia (CIN) (N = 7) and high-grade CIN (N = 7). The carcinomas were either moderately (N = 3) or poorly differentiated (N = 5). The non-neoplastic controls were normal squamous epithelium from cases with uterine prolapse (N = 7) and normal squamous epithelium not affected by the infective or neoplastic areas of some of the cases with wart virus infection (N = 2) and carcinoma (N = 2). Moderate to strong cytoplasmic and, occasionally, nuclear immunostaining for the nm23-H1 protein was seen in all cells above the basal layer of the normal squamous epithelium. However, most of the cervical SCC show a relative reduction in nm23-H1 immunoreactivity (7/8 cases; 88%). This difference in nm23-H1 expression was statistically significant (P = 0.0006; Chi-squared test with continuity correction). All of the cases with wart virus infection (N = 5; 100%) displayed moderately strong nm23-H1 immunostaining throughout the squamous epithelium except for the basal layer where no staining was observed. The cases that had low-grade squamous dysplasia of the cervix (CIN I-II) (N = 7; 100%) also displayed moderate to strong nm23-H1 immunoreactivity in the epithelium except for the basal layer (CIN I) or the lower two-thirds of the epithelium (CIN II). nm23-H1 Immunoreactivity was either absent or was significantly reduced in all of the high-grade CIN (CIN III) cases (N = 7; 100%) in which only the non-dysplastic superficial third of the squamous epithelium displayed nm23-H1 immunolabeling. The difference in nm23-H1 expression between low-grade and high-grade CIN cases was statistically significant (P = 0.0013; Chi-squared test with continuity correction). Similarly, the difference between low-grade CIN and SCC cases in the expression of nm23-H1 was also significant (P = 0.0041; Chi-squared test with continuity correction). However, no statistically significant difference in nm23-H1 immunoreactivity was found between cases of high-grade CIN and SCC. In conclusion, nm23-H1 protein immunoreactivity is reduced in high-grade CIN and cervical SCC but not in low-grade CIN. These findings suggest that reduced expression of the protein may be important early in the sequential development of cervical squamous neoplasia.
利用常规链霉亲和素-生物素免疫组织化学方法以及针对nm23-H1蛋白的多克隆抗体，研究人nm23-H1基因编码的17kDa蛋白在子宫颈癌前病变和浸润性鳞状细胞癌（SCC）（N = 8）中的免疫组织化学表达差异。癌前病变包括因疣病毒感染导致的挖空细胞异型增生（N = 5）、低度宫颈上皮内瘤变（CIN）（N = 7）和高度CIN（N = 7）。这些癌组织分化程度中等（N = 3）或较差（N = 5）。非肿瘤对照为子宫脱垂病例的正常鳞状上皮（N = 7）、部分疣病毒感染病例及癌病例中未受感染或肿瘤区域影响的正常鳞状上皮（疣病毒感染病例N = 2，癌病例N = 2）。在正常鳞状上皮基底层以上的所有细胞中均可见到nm23-H1蛋白呈中度至强阳性的胞质染色，偶尔也有核染色。然而，大多数宫颈SCC显示nm23-H1免疫反应性相对降低（7/8例；88%）。nm23-H1表达的这种差异具有统计学意义（P = 0.0006；连续性校正卡方检验）。所有疣病毒感染病例（N = 5；100%）在整个鳞状上皮中均显示中度至强nm23-H1免疫染色，但基底层未观察到染色。宫颈低度鳞状上皮发育异常（CIN I-II）病例（N = 7；100%）除基底层（CIN I）或上皮下三分之二（CIN II）外，上皮中也显示中度至强nm23-H1免疫反应性。在所有高度CIN（CIN III）病例（N = 7；100%）中，nm23-H1免疫反应性要么缺失，要么显著降低，其中只有鳞状上皮无发育异常的浅表三分之一显示nm23-H1免疫标记。低度和高度CIN病例之间nm23-H1表达的差异具有统计学意义（P = 0.0013；连续性校正卡方检验）。同样，低度CIN和SCC病例之间nm23-H1表达的差异也具有统计学意义（P = 0.0041；连续性校正卡方检验）。然而，高度CIN和SCC病例之间在nm23-H1免疫反应性方面未发现统计学上的显著差异。总之，nm23-H1蛋白免疫反应性在高度CIN和宫颈SCC中降低，但在低度CIN中未降低。这些发现表明，该蛋白表达的降低可能在宫颈鳞状肿瘤的连续发展早期具有重要意义。
