고려대학교 안암병원 부인암크리닉을 내원한 환자들중 자궁경부 상피내종양이나 침윤암으로 진단되 수술을 시행하였던 60예를 대상으로 파라핀 포매 조직을 이용하여 HPV 16/18의 E6, E7과 p53, Rb 단백의 발현율을 면역 조직화학법으로 염색하고 광학현미경으로 검색하여 다음과 같은 결과를 얻었다. 1. p53 단백의 발현율은 편평상피암 중 상피내종 양이 29.4%(5/17), 미세침윤암이 75.0%(6/8), 침윤암이 68.0%(17/25) 등으로 암이 진행될수록 발현율이 유의 하게 높음을 알 수 있었다(p＝0.007). 선암은 50% (2/ 4), 편평상피선암은 40%(2/5)의 발현율을 보였다. 2. Rb단백의 발현율은 편평상피암의 경우 상피내 종양이 70.6%(12/17), 미세침윤암 50%(4/8), 침윤암 20%(5/25) 등으로 종양이 진행될수록 발현율이 감소 하였다(p＝0.003). 선암의 경우는 발현율이 25%(1/4), 편평상피선암은 침윤암의 경우 40%(2/5)의 발현율을 보였다. 3. HPV 16/18의 E6 단백의 발현율은 편평암 상피 내종양이 35.3%(6/17), 미세침윤암은 50%(4/8), 침윤 암은 60%(15/25) 등으로 암이 진행될수록 발현율이 높음을 알 수 있었으나 통계학적인 유의성은 없었다 (p＝0.136). 선암은 25%(1/4), 침윤암은 60.0%(3/5)의 발현율을 보였다. 4. HPV 16/18 E7 단백의 발현율은 편평상피내 종 양인 경우 70.6%(12/17), 미세침윤암은 87.5%(7/8), 침 윤암은 92%(23/25)로 암이 진행될수록 증가됨을 알 수 있었으나 서로간에 통계적인 유의성은 없었다(p ＝0.063). 선암에서는 25%(1/4), 편평상피선암은 60% (3/5)의 발현율을 보였다. 5. HPV 16/18 E6 단백과 p53 단백 발현율은 서로 간에 통계적인 유의성을 관찰할 수 없었다(p＝0.07). 6. HPV 16/18 E7 단백과 Rb 단백 발현율에서도 서로간에 통계적인 상관관계를 관찰할 수 없었다(p ＝0.19). 이상의 결과로 미루어 종양억제유전자인 p53과 Rb 유전자가 자궁경부암의 발암화 현상이 진행되며 이와 더불어 HPV 16/18의 E6와 E7 단백도 자궁경부 암의 진행에 관여할 것으로 추축된다.

Human papillomavirus (HPV) infection in women is known to be a causative factor in the initiation and progression of uterine cervical cancer by producing proteins in host cells to effect transformation and immortalization at the cellular level resulting in cancerous tumor growth. Among the types of the HPV, type 16 and type 18 are classified as high risk types because they are frequently found in cervical lesions with high grade dysplasias and invasive carcinomas. However, it is impossible to ascertain by host histologic or cellular changes which type of HPV is infected. The HPV genome is composed of six open reading frames (ORF`s) named as E1, E2, E4, E5, E6, and E7 in the early region, of which the E6 and E7 ORF`s interact with tumor suppressor proteins p53 and retinoblastoma (Rb) gene products repectively, and stimulate the cell cycle. In this study, immunohistochemical staining of E6, E7, p53, and Rb proteins was conducted to determine the rate of expression of HPV oncoproteins, correlation with the tumor supressor proteins, and relationship in dysplasia and invasive uterine cervical cancer. Sixty cases of carcinoma in situ (CIS) and invasive cacinoma were immunohistochemically stained, and the results obtained were as follows: 1) p53 was positive in 5 of 17 cases (29.4%) of CIS, in 6 of 8 cases of microinvasive carcinoma (75.0%), and in 17 of 25 cases of invasive carcinoma (68.0%), showing significantly different p53 protein expression between the dysplasia and invasive cancer groups (p＝0.007). 2) Rb protein was positive in 12 of 17 cases (70.6%) of CIS, in 4 of 8 cases of microinvasive carcinoma (50.0%), and in only 5 of 25 cases of invasive carcinoma (20.0%), showing that there was significantly different Rb protein expression between the CIS and invasive cancer groups (p＝0.003). 3) E6 protein of HPV type 16/18 was expressed in 6 of 17 cases (35.3%) of CIS, in 4 of 8 cases of microinvasive carcinoma (50.0%), and in 15 of 25 cases of invasive carcinoma (60.0%), but there was no significant difference in expression between the CIS and invasive cancer groups (p＝0.136). 4) E7 protein of HPV type 16/18 was expressed in 12 of 17 cases (70.6%) of CIS, in 7 of 8 cases of microinvasive carcinoma (87.5%), and in 23 of 25 cases of invasive carcinoma (92.0%), but there was no significant difference in expression between the CIS and invasive cancer groups (p＝0.063). 5) There was no statistical significance between HPV type 16/18 E6 protein and p53 protein expression (p＝0.07). 6) There was also no statistical significance between HPV type 16/18 E7 protein and Rb protein expression (p＝0.19). The above results suggest that limited action by mutation of the tumor suppressor genes p53 and Rb seems to play a role in the progression of uterine cervical cancer, and E6 and E7 proteins may also play a role. However, this study was unable to reveal a significant role of p53 and Rb protiens in adenocarcinoma of the uterine cervix, and it is recommended that further studies should be undertaken.