Early progression stage of malignancy of uterine cervical dysplasia as revealed by immunohistochemical demonstration of increased DNA-instability

The degree of DNA-instability as revealed by the immunohistochemical staini ng with anti-single-stranded DNA antibody after acid hydrolysis (DNA-instab ility test) was used as a marker of malignancy. This was applied to mild dy splasia (42 cases), moderate dysplasia (43 cases), severe dysplasia (27 cas es), squamous cell carcinoma in situ (CIS) (21 cases), invasive squamous ce ll carcinoma (SCC) (31 cases) and normal (7 cases) human uterine cervix. Th e expression of tumour suppressor gene p53 and oncogene bcl-2 was detected immunohistochemically. Proliferative activity was evaluated by PCNA immumoh istochemistry and the quantitative analysis of the number, mean area, the l argest area and maximum shape irregularities of AgNOR in a nucleus were per formed for all these cases. The distribution of numeric chromosomal aberrat ions of chromosome 17 was also investigated in some of these cases. The res ults showed that 31 SCC (100%), 21 CIS (100%), 21 severe dysplasia (77.77%) , 28 moderate dysplasia (65.11%), and 14 mild dysplasia (33.33%) were posit ively stained by the DNA-instability test diffusely or sporadically, indica ting their malignancy. Reflecting the malignant character, these cases show ed a remarkable increase in the PCNA-index with the loss of polarity of PCN A positive cell distribution and also an increase in number, mean and large st sizes and maximum shape irregularity of AgNOR dots. The mean chromosome index for chromosome 17, p53 and bcl-2 immunostaining positivity were also found to be significantly increased in moderate and severe dysplasia and in cancerous cases in comparison to normal and mild dysplasia cases. Moreover , the DNA-instability-test positive dysplasia cases showed statistically si gnificant increased values of PCNA-index, AgNOR parameters, mean chromosome index, p53 and bcl-2 expression in comparison to those of DNA-instability- test negative dysplasia cases. In conclusion, some mild dysplasia (33.33%) and most of the moderate (65.11 %) and severe dysplsia (77.77%) were regarded as malignant in nature, exist ing at an early stage of progression of malignancy.