Relationship Between Type Of HPV And Activity Of Telomerase In Condyloma Acuminatum,Bowenoid Papulosis,Bowen's Disease And Vulvar Squamous Cell Carcinoma

Objectiveto detect and compare the expression of human telomerase reverse transcriptase(hTERT) among normal foreskin, condyloma acuminatum(CA), bowenoid papulosis(BP), Bowen's disease(BD) and vulvar squamous cell carcinoma, and examine the type of HPV in lesions, to explore: 1. the expression of telomerase in normal tissue, benign tumor and malignant carcinoma and its clinical significance, 2. the effect on the activity of telomerase by the type of HPV and possible mechanism of high-risk HPV's inducing tumorigenesis. Methods1. All cases diagnosed as CA, BP, BD or SCC in the last five years in our hospital were collected and the cases of each disease were 40, 30, 16 and 16, respectively. 16 normal foreskin specimens obtained from those whose foreskins were annularly cut off in the clinic operating room were fixed by formaldehyde and embedded by paraffin.2. The expression of hTERT in keratinocytes, representing the activity of telomerase, was detected by immunohistochemistry technique.3. The expression of hTERT was compared among normal skin, CA, BP, BD and SCC.4. HPV16, 18 which were used as the representatives of high-risk HPV were tested by polymerase chain reaction(PCR).5. The expression of hTERT was compared between HPV16, 18-positive group and HPV16, 18-negative group. Also, each group was compared with normal skin.Results1. Location and intensity of immunohistochemical stainPositive expression was located mainly in the plasma and the nuclear, partially on the membrane of keratinocytes. Normal foreskin specimens were all negative; In CA, only a few cells were dyed with light color and most of them were vacuole cells; In BP and BD, more positive cells with deeper color were observed and most of them were atypical cells in every layer of the epidermis; In SCC, positive-dyed cells were skattered around and the color was deeper than that in BP andBD.2. Positive rates of all groupsThe positive rates in normal foreskin, CA, BP, BD and SCC were 0%, 32.5%, 53.3%, 62.5% and 87.5%, respectively.3. Result of comparison of positive expression intensity among all groups There was significant statistic difference in the expression of hTERT betweennormal foreskin and all the other groups. Also, the expression of hTERT was significantly different between CA and all the other groups. There was no significant statistic difference between BP and BD and also between BD and SCC, but hTERT expression of BP was significantly lower than that of SCC.4. Result of HPV 16 ^ 18 examination in the lesionsThe positive rates of HPV 16 in CA and BP were 17.5%(7/40) and 46.7%(14/30). No HPV18 was found in both CA and BP.5. Result of comparison of positive expression intensity betweenHPV16-positive group and HPV16-negative group and also between the two and normal foreskinIn CA, there was significant statistic difference in the expression of hTERT between HPV16-positive group and HPV16-negative group; the same result was found in BP. When considering CA and BP as a whole , the result was still the same. In addition, all the above groups were significantly higher than normal foreskin in the expression of hTERT.6. Result of comparison of positive expression intensity between HPV16-positive BP and HPV16-positive CA and also between HPV16-negative BP and HPV16-positive CA.The expression of hTERT was significantly different between CA and BP both with HPV16 infection. But there was no significant statistic difference between HPV16-positive CA and HPV16-negative BP. Conclusions1. The expression of telomerase in normal skin, benign tumor and malignant carcinoma rise gradually, which suggests that the expression of telomerase plays an important role in both cell proliferation and immortalization. More research is still needed to judge the limit between benign tumor and malignant carcinoma by telomerase detection.2. In the activity of telomerase, BP was significantly higher than CA but lower than SCC, which suggests that BP is situated between benign squamous cell tumor and malignant squamous cell carcinoma and to some extent BP has the tendency to become malignant. Long and close observation should be put on such patients.3. The rate of high-risk HPV infection in BP is higher than that in CA, and in both diseases HPV 16 is the major type.4. Telomerase activity of HPV16-positive group was significantly higher than that of HPV 16-negative group and they both were significantly higher than that of normal foreskin, which suggests that high-risk HPV infection can activate telomerase more greatly and activating telomerase might be one of the early eventsduring high-risk HPV's inducing tumorigenesis.5. The expression of hTERT was significantly different between CA and BP both with HPV16 infection. But there was no significant statistic difference between HPV16-positive CA and HPV16-negative BP. This suggests that in addition to HPV16 infection, other factors which also activate telomerase contribute to the development of BP. They together make BP and CA show different clinical and histopathological manifestations.