The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans.
Acute Disease ; Adenocarcinoma/virology ; Cell Line ; DNA, Viral/*genetics/isolation & purification ; Humans ; Korea ; Leukemia/*virology ; Leukemia Virus, Bovine/*genetics ; Leukemia, Lymphocytic, Acute/virology ; Leukemia, Myeloid/virology ; Leukemia, Myeloid, Chronic/virology ; Lung Neoplasms/*virology ; Polymerase Chain Reaction/methods ; Proviruses/*genetics

OBJECTIVEConducting the gene characterization of the E6 and E7 gene of human papillomavirus 16 (HPV16) isolated from 15 cases of cervical cancer at Beijing.

METHODSOverlapping primers were designed according to the full-length genomes of E6 and E7 from the GenBank and PCR was used to amplify the E6 and E7 fragments. TA clone was used to select a purified clone in order to have better and valuable sequencing results. Nucleotide and amino acid sequence were analyzed by the Sequencer, Bioedit, Mega et al.

RESULTS8 of 15 (8/15) cervical samples contained HPV E6 and E7 gene, and 4 had Asian type like and 4 had Europe prototype like. There were two nucleotide mutation at E6 position 178 (T-->G,D25E) and at E7 position 647 (A-->G, N29S) in 4 Asian type like viruses. There were one nucleotide mutation at E6 position 335 (C-->T, H78Y) in 1 of 4 Europe prototype like virus. In the cervical cancer samples, 8 of 15 contained the HPV16E 6 and E7 gene. HPV16 E6 and E7 can not be detected in denosquamous carcinoma and adenocarcinoma.

CONCLUSIONHPV16 is the main etiology of the cervical carcinoma. The HPV16 infectious ratio of squamous carcinoma is more than the ratio of adenocarcinoma. 178th nucleotide in E6 gene is the very important site to distinguish the Asia and the Europe prototype strain like. 178 nucleotide in E6 and 647 nucleotide in E7 are the frequent mutation site in cervical carcinoma. Analysis based on the E6 and E7 gene sequence of HPV 16 isolates suggests that naturally occurring sequence variants of E6 and E7 gene may have identify the oncogenic properties.

Adenocarcinoma ; virology ; Carcinoma, Squamous Cell ; virology ; China ; Female ; Human papillomavirus 16 ; chemistry ; genetics ; isolation & purification ; Humans ; Mutation ; Oncogene Proteins, Viral ; chemistry ; genetics ; Papillomavirus E7 Proteins ; Papillomavirus Infections ; virology ; Repressor Proteins ; chemistry ; genetics ; Sequence Homology, Amino Acid ; Uterine Cervical Neoplasms ; virology

The pathogenesis of endocervical glandular lesions are not clearly understood. The aims of this study are to evaluate the etiologic role of human papillomavirus (HPV) 16/18 and the relationship of HPV 16/18, p53 and MIB-1 expressions in endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma. The materials included 14 endocervical adenocarcinoma and 5 AIS and 18 high grade EGD and 39 low grade EGD. Immunohistochemistry for p53 and MIB-1, and in situ PCR for HPV 16/18 were done. HPV 16/18 positivity was 84.2%, 16.7% and 17.9% in malignant glandular lesion (adenocarcinoma and AIS), high grade EGD and low grade EGD, respectively. P53 protein expression rates of malignant glandular lesions, high grade EGD and low grade EGD were 31.6%, 11.1%, and 0%, respectively. High MIB-1 labelling index was found in 73.7% of malignant glandular lesions, but in only 5.7% and 3.6% of high and low grade EGD, respectively. There were statistically significant differences in HPV 16/18, p53 and MIB-1 expressions between malignant endocervical glandular lesions and EGD, but no significant difference in p53 and MIB-1 expressions in relation to HPV 16/18 expression. In malignant endocervical glandular lesions, HPV 16/18 infection may be a major causative factor, but not be related to p53 and MIB-1 expressions.
Adenocarcinoma/pathology/physiopathology/*virology ; Carcinoma, Squamous Cell/pathology/physiopathology/virology ; Cervix Neoplasms/pathology/physiopathology/*virology ; Female ; Human ; Nuclear Proteins/analysis/*genetics ; Oncogene Proteins, Viral/genetics ; *Papillomavirus, Human ; Papovaviridae Infections/*pathology/physiopathology ; Protein p53/analysis/*genetics ; Tumor Virus Infections/*pathology/physiopathology

OBJECTIVESTo evaluate the significance of p16(INK4A) protein expression and positivity for HPV DNA in distinguishing between endocervical and endometrial adenocarcinoma.

METHODSExpression of p16(INK4A) protein in 30 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma was assessed by immunohistochemistry. In-situ hybridization for human papillomavirus (HPV) DNA was also performed in 20 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma.

RESULTSThe positive rate for p16(INK4A) in endocervical adenocarcinoma was 70% (21/30), as compared with 30% (3/10) in endometrial adenocarcinoma. The tumor cells in endocervical adenocarcinoma showed diffuse and strong expression of p16(INK4A) protein with both cytoplasmic and nuclear staining. In contrast, the endometrial adenocarcinoma cells showed patchy and weak expression of p16(INK4A). On the other hand, HPV DNA (type 16 or 18) was detected by in-situ hybridization in 9 (45%) of the 20 cases of endocervical adenocarcinoma and none of the 10 cases of endometrial adenocarcinoma.

CONCLUSIONSThe expression of p16(INK4A) protein is significantly higher in endocervical adenocarcinoma than in endometrial adenocarcinoma. This expression pattern can serve as a useful immunohistochemical marker in the differential diagnosis. p16(INK4A) protein immunohistochemistry appears to be more sensitive than HPV DNA testing in distinguishing between endocervical and endometrial adenocarcinoma, especially in biopsy or curettage specimens.

Adenocarcinoma ; diagnosis ; genetics ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; DNA, Viral ; analysis ; Endometrial Neoplasms ; diagnosis ; genetics ; virology ; Female ; Gene Expression Regulation, Neoplastic ; Human papillomavirus 16 ; genetics ; Human papillomavirus 18 ; genetics ; Humans ; In Situ Hybridization ; Uterine Cervical Neoplasms ; diagnosis ; genetics ; virology

OBJECTIVETo investigate the infection of the high risk human papillomavirus (HPV) in the specimen of the clear cell carcinoma of the cervix.

METHODSWe extracted the nucleic acids in the formalin-fixed and paraffin-embedded specimens from a 37-year-old patient with clear cell carcinoma of the cervix and detected the HPV genotype with the nested PCR.

RESULTSWe identified HPV18, a high-risk genotype, in the specimens.

CONCLUSIONThe HPV detection with the nested PCR was available for identification of the HPV genotype(s) in the paraffin-embedded specimens of clear cell carcinoma of the cervix (CCCC) with a high accuracy and sensitivity.

Adenocarcinoma, Clear Cell ; diagnosis ; virology ; Adult ; Female ; Genotype ; Human papillomavirus 18 ; genetics ; isolation & purification ; Humans ; Papillomavirus Infections ; diagnosis ; virology ; Paraffin Embedding ; Polymerase Chain Reaction ; Sensitivity and Specificity ; Uterine Cervical Neoplasms ; diagnosis ; virology

OBJECTIVETo evaluate clinical characteristics, prognosis, prognostic factors, and the ideal treatment of the young patients with cervical malignant tumor.

METHODSWe analyzed retrospectively 52 cervical malignant tumor patients younger than 35 years (study group) and 45 cervical carcinoma patients older than 50 years (control group) who were admitted in Peking Union Medical College Hospital from 1985 to 2002. The data were analyzed statistically by SPSS10.0. The ovarian functions were evaluated by the questionnaire and the serum sex hormone assay.

RESULTSIn study group, the median age was (31.0 +/- 0.6) years old. The most common clinical symptoms were contact bleeding and irregular bleeding; 55.8% of patients had more than one symptom. HPV positive rate was 20.5%, which was higher than control group significantly (P < 0.05). The percentage of advanced stage (stage II b-stage IV b) of disease in study group and control group were 30.8% and 22.2%, respectively, the difference was significant (P < 0.05). The most common histological type was squamous cell carcinoma (71.2%) in study group, while the percentage of non-squamous cell carcinoma (43.8%) in patients younger than 30 years was much higher than control group (P < 0.05). All the histological type was non-squamous cell carcinoma in the patients younger than 25 years. Histological grade showed that G1, G2, and G3 were 21.2%, 54.5%, and 24.2% respectively in study group. The percentage of bulky cervix (tumor diameter > 4 cm) in study group and control group was 27.9% and 2.7% respectively (P < 0.005). The overall 5-year survival rates were 75.7% in study group, lower than control group (P < 0.05). The COX hazards regression model showed histological type (P = 0.003) and bulky cervix (P = 0.001) were of significant prognostic values.

CONCLUSIONSThere are more advanced stage carcinoma and non-squamous cell carcinoma patients with poor prognosis in study group. The treatment to younger patients should be concerned individually, as well as preservation of reproductive and female endocrine function should be considered.

Adenocarcinoma ; diagnosis ; surgery ; virology ; Adult ; Age Factors ; Carcinoma, Squamous Cell ; diagnosis ; surgery ; virology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Ovarian Function Tests ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; Prognosis ; Regression Analysis ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms ; diagnosis ; surgery ; virology

The relationship between Human papillomavirus (HPV) 16 infection and the natural course of colorectal adenocarcinoma has not been fully defined. In this study, the HPV 16 E7 DNA was detected in 82 patients with primary colorectal adenocarcinoma to study the relationship between HPV 16 infection and colorectal carcinoma. Samples were taken from both the tumors and the adjacent normal mucosa in the same patient. Polymerase chain reaction (PCR) was used to amplify the HPV16 E7 DNA fragment. The PCR products were gel-purified and sequenced for HPV genotyping. DNA sequence analysis indicated that PCR product was 297 bp. It was the equivalent of 562-858th pairs in the HPV 16 primitive sequences. Our results showed HPV16 E7 DNA expression was significantly higher in colorectal carcinoma (42/82) than in adjacent normal mucosa (4/82). The correlation was found between HPV16 E7 expression and tumor's location; the positive rate was 18.18% in the ascending colon carcinoma group and 64.10% in the rectal carcinoma group. High HPV16 E7 expression was also associated with lower Dukes stage (P < 0.01). These results indicated that there was correlation between colorectal adenocarcinoma and HPV 16 infection. HPV16 infection was relatively higher in the colorectal carcinoma and rare in the adjacent normal mucosa. Specimens expressing higher levels of HPV 16 E7 DNA were associated with lower Dukes stage and more distal location.
Adenocarcinoma ; metabolism ; virology ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; virology ; DNA, Viral ; analysis ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Oncogene Proteins, Viral ; biosynthesis ; genetics ; Papillomaviridae ; isolation & purification ; Papillomavirus E7 Proteins ; Papillomavirus Infections ; metabolism ; virology

OBJECTIVETo evaluate the correlation of the expression of homeodomain-interacting protein kinase 2 (HIPK2) with human papillomavirus (HPV) infection and apoptosis in cervical cancer.

METHODSFormalin-fixed, paraffin embedded tissue samples from 50 cervical cancers and 15 normal uterine cervix cases were obtained. Apoptosis was quantified by TdT-mediated dUTP nick end labeling (TUNEL) assay and the expression of HIPK2 as well as HPV by immunohistochemical staining.

RESULTSHIPK2 protein expression was detected in 88.0% (44/50) of cervical cancers and 6.7% (1/15) of normal cervical tissues. HPV was found in 78.0% (39/50) of cervical cancers and 20.0% (3/15) of normal cervical tissue samples. The expression of HIPK2 protein was significantly and positively correlated with HPV presence (r=0.467, P<0.01), but negatively with apoptotic index (r=-0.370, P<0.05).

CONCLUSIONHIPK2 protein expression is positively correlated with HPV infection, but negatively with apoptotic index in cervical cancers. Therefore, HIPK2 may be involved in the mechanism of apoptosis in cervical cancer and may play an important role in cervical carcinogenesis.

Adenocarcinoma ; metabolism ; pathology ; virology ; Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Carrier Proteins ; metabolism ; Cervix Uteri ; metabolism ; Female ; Humans ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Proliferating Cell Nuclear Antigen ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology

Adenocarcinoma ; genetics ; pathology ; virology ; Carcinoma in Situ ; genetics ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; genetics ; pathology ; virology ; Cervix Uteri ; pathology ; virology ; Cytological Techniques ; DNA, Viral ; analysis ; Female ; Follow-Up Studies ; Humans ; Neoplasm Grading ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; Uterine Cervical Neoplasms ; genetics ; pathology ; virology

BACKGROUND: Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders and nasopharyngeal carcinoma. Recently, some gastric cancer cells were observed to contain the EBV sequence. We detected EBV in gastric cancer by using PCR to determine the frequency of EBV-associated gastric cancer, and performed immunohistochemical staining for the latent membrane protein (LMP1), p53 and CD44 to investigate the possible mechanism in EBV-associated gastric cancer. METHODS: Eighty-seven formalin-fixed and paraffin-embedded blocks (40 gastric adenocarcinomas, 34 adjacent normal tissues, 13 metastatic lymph nodes) from 40 surgically resected gastric specimens were studied. All patients were diagnosed with gastric cancer at the Kang-Nam St. Mary's Hospital between April 1995 and April 1997. After DNA was extracted from each paraffin block, we performed PCR and immunohistochemical staining for the LMP1, p53 and CD44. RESULTS: EBV was detected in 4 of 40 cases (10%). In 1 of 4 EBV-positive cases, EBV was also detected in a metastatic lymph node. The immunohistochemical staining for the LMP1, p53 and CD44 were negative in all the EBV-positive cancer patients. Of the patients having these cancers, 2 had a poorly differentiated adenocarcinoma with a lymphoepithelioma-like morphology. DISCUSSION: The frequency of EBV-associated gastric cancer is about 10% in Korea. Considering the negative result of the immunohistochemical staining for the LMP1, p53 and CD44, EBV-associated gastric cancer seems to have a different mechanism of tumorigenesis from ordinary gastric cancer or other EBV-associated cancers. This specific mechanism must be determined by further large scale studies.
Adenocarcinoma/metabolism/*virology ; Adult ; Antigens, CD44/metabolism ; Female ; Herpesvirus 4, Human/*isolation & purification ; Human ; Immunohistochemistry ; Male ; Middle Aged ; Polymerase Chain Reaction ; Protein p53/metabolism ; Stomach Neoplasms/metabolism/*virology ; Viral Matrix Proteins/metabolism