OBJECTIVEThe aim of this study was to investigate the characteristics of p16 and PR immunoreactivity and HPV infection in endocervical adenocarcinoma.

METHODSParaffin blocks of 62 patients with endocervical adnocarcinoma treated in the Cancer Institute and Hospital, Chinese Academy of Medical Sciences from year 2005 to year 2010 were collected. p16 and PR immunostaining and HPV detecting by SPF-10 PCR were conducted on all cases.

RESULTSHPV infection rate of the 62 endocervical adnocarcinoma cases was 74.2% with four cases combined with CIN3. Among the 46 HPV-positive cases, there were 22 cases of HPV18 infection (47.8%), 14 cases of HPV16 infection (30.4%), one case of HPV59 infection (2.2%). and nine multiple HPV infection cases (19.6%). The mean age of the 16 HPV-negative cases was (49.6 ± 10.5)year, while the mean age of the 46 HPV-positive cases was (42.8 ± 9.7)year, showing a significant difference between the two subgroups (P = 0.022). The positive rate of p16 infection was 80.6%. Association analysis showed that the results of p16 and HPV test were independent to each other (P = 0.077). The positive rate of PR was 3.2%. Among the 62 cases, there were 24 cases containing normal cervical glands, with 19 cases PR-positive in the normal cervical glands and the positive rate was 79.2%. The difference of PR positivity between neoplastic glands and normal glands was statistically significant by Chi-square test (P < 0.01) .

CONCLUSIONSThe HPV infection rate of endocervical adnocarcinoma is 74.2%, and the major subtypes were HPV16 and HPV18 infection. p16 immunoreactivity in endocervical adenocarcinoma maybe not the proof of high-risk HPV-related neoplasm. PR staining can be used as a reference designator to differentiate between neoplastic and normal cervical glands.

Adenocarcinoma ; metabolism ; pathology ; virology ; Adult ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Female ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; Immunohistochemistry ; Middle Aged ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; virology ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology

OBJECTIVETo investigate the clinicopathological features and prognostic factors of primary clear cell carcinoma of the liver (PCCCL).

METHODSThe clinical data of 41 PCCCL patients who underwent hepatic resection for PCCCL from October 1998 to June 2012 in our department were retrospectively analyzed. There were 31 male and 10 female patients. The median age was 56 years (range, 25 to 80 years), and the diagnosis was confirmed by postoperative pathological examination. The data of 106 well or moderately differentiated non-clear cell hepatocellular carcinoma (HCC) patients and 86 poorly differentiated non-clear cell HCC patients who underwent hepatic resection in the same period in our hospital in the same period were compared. The χ(2) test or Fischer's exact test, as appropriate, was used to compare group frequencies. Survival analysis was estimated by Kaplan-Meier method. Cox proportional hazards model was used in multivariate analysis.

RESULTSThe proportion of fibrous capsule formation in the PCCCL tumors (46%, 19/41) was significantly higher than that of the other two groups (P < 0.05), whereas the PCCCL group had a lower rate of intravascular tumor embolus (2/41) and vascular invasion (1/41) (P < 0.05). The median survival time of PCCCL group was 65 months, the 1-, 3-, 5-year survival rates for PCCCL patients were 90.2%, 67.4% and 42.0%, significantly better than that of poor differentiated NCCHCC group's (82.9%, 33.3%, 7.2%, P < 0.01). However, there were no statistic significant differences between PCCCL group and well or moderately differentiated NCCHCC group (84.7%, 55.7%, 34.4%, P > 0.05). Tumor capsule formation was an independent favorable prognostic factor. In contrast, preoperative serum α-fetoprotein (AFP) level and hepatitis B virus infection were independent unfavorable prognostic factors for PCCCL.

CONCLUSIONSPCCCL is a rare, low degree malignant pathological subtype of HCC. Surgical resection may achieve favorable prognosis and even long-term survival.

Adenocarcinoma, Clear Cell ; blood ; pathology ; surgery ; virology ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; blood ; pathology ; surgery ; virology ; Female ; Follow-Up Studies ; Hepatectomy ; Hepatitis B ; Humans ; Liver Neoplasms ; blood ; pathology ; surgery ; virology ; Male ; Middle Aged ; Neoplastic Cells, Circulating ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; alpha-Fetoproteins ; analysis

PURPOSE: Antimicrobial peptides have an important role in self-protection of the ocular surface. Human cationic antimicrobial protein (hCAP)-18 is a linear, alpha-helical peptide that consists of a conserved pro-sequence called a cathelin-like domain and a C-terminal peptide named LL-37. We investigated the in vitro anti-adenoviral activity of hCAP-18/LL-37 in several adenovirus types, inducing keratoconjunctivitis. METHODS: A549 cells were used for viral cell culture, and human adenovirus (HAdV) types 3 (HAdV3, species B), 4 (species E), 8, 19a, and 37 (species D) were used. The cytotoxicity of LL-37 was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay to obtain 50% cytotoxic concentration. After pretreatment of A549 cells with serial dilutions of LL-37 for 24 hours, adenovirus was cultured for seven days, and adenoviral DNA was quantitatively measured by real-time polymerase chain reaction (PCR). RESULTS: The 50% effective concentration of LL-37 obtained by real-time PCR ranged between 118 and 270 microM. LL-37 showed a significant inhibitory effect on adenoviral proliferation in all adenovirus types except HAdV4 in a dose-dependent manner. CONCLUSIONS: LL-37 has significant inhibitory activity against HAdV3, 8, and 19, which induce keratoconjunctivitis. These results indicate that hCAP-18/LL-37 may be a possible candidate for the treatment of HAdV keratoconjunctivitis.
Adenocarcinoma ; Adenoviridae/*drug effects/*genetics ; Adenoviridae Infections/*drug therapy/virology ; Antimicrobial Cationic Peptides/*pharmacology ; Cell Line, Tumor ; DNA, Viral/genetics ; Humans ; Keratoconjunctivitis/*drug therapy/virology ; Lung Neoplasms ; Reverse Transcriptase Polymerase Chain Reaction/methods

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

OBJECTIVETo evaluate the H. pylori and Epstein-Barr virus infection in cardiac and distal gastric adenocarcinoma tissues in residents in Cixian county, a high risk area of esophageal cancer in Hebei province, and to explore the putative role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of adenocarcinoma at different subsites of stomach.

METHODSH. pylori and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were determined by Elivision(TM) plus immunohistochemical staining in 190 gastric adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein-Barr virus infection and the subsite, Laurén type as well as other clinicopathological features of gastric adenocarcinoma were analyzed.

RESULTSNo significant difference was found between the H. pylori detection rates in cardiac and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate of H. pylori in intestinal type was significantly higher than that in the diffuse type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study.

CONCLUSIONSNo significant differences in H. pylori and EBV-LMP1 infections were found between cardiac and distal gastric adenocarcinomas in Cixian county. H. pylori infection is related with the intestinal type of distal gastric adenocarcinoma.

Adenocarcinoma ; microbiology ; pathology ; virology ; Aged ; Cardia ; China ; Epstein-Barr Virus Infections ; pathology ; Female ; Helicobacter Infections ; pathology ; Helicobacter pylori ; isolation & purification ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; microbiology ; pathology ; virology ; Viral Matrix Proteins ; metabolism

OBJECTIVETo investigate the clinicopathological features, diagnosis, treatment and prognosis of primary clear cell carcinoma of the liver (PCCCL).

METHODSThe clinicopathological data of 24 cases with pathologically proven PCCCL in the First Affiliated Hospital of Guangxi Medical University from May 1996 to December 2003 were collected and analyzed.

RESULTSThere were 21 males and 3 females in this group, with an average age of 46 years (range: 30 approximately 78 years). HBV infection was detected in 83.3%, and AFP expression was found in 75.0% of them. Of the 24 cases, 28 tumors were found with an average size of (6.64 +/- 5.54) cm. Liver cirrhosis was found in 75.0% of the patients. Macroscopic and microscopic tumor thrombi were found in 20.8% and 29.2%, respectively. Lymph node metastasis was found in 4.2% of the patents. The 1-, 3-, and 5-year overall survival rates of the 24 cases were 75.0%, 41.7% and 27.8%, respectively, with a median survival time of 29 months.

CONCLUSIONThe clinical characteristics of primary clear cell carcinoma of the liver are similar to that of common hepatocellular carcinoma. It is difficult to be diagnosed preoperatively and final diagnosis depends on pathological examination. Surgical resection is an effective way to achieve favorable treatment outcome and even long-term survival.

Adenocarcinoma, Clear Cell ; blood ; pathology ; surgery ; virology ; Adult ; Aged ; Female ; Follow-Up Studies ; Hepatectomy ; methods ; Hepatitis B ; Humans ; Liver Neoplasms ; blood ; pathology ; surgery ; virology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Rate ; alpha-Fetoproteins ; analysis

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

OBJECTIVETo study the death mode of human hepatocellular carcinoma Hep-3B cells and human lung adenocarcinoma A549 cells induced by bluetongue virus strain HbC3 (BTV-HbC3) and the mechanism of its action.

METHODSBTV-HbC3 was used to infect the tumor cells, and the cytopathic effects (CPE) was observed. TUNEL staining was used to detect the apoptosis of tumor cells induced by BTV-HbC3. The changes of endoplasmic reticulum and nuclei treated with BTV-HbC3 were further examined by laser scanning confocal microscopy. The activities of caspase-3/7, caspase-8 and caspase-9 were determined by fluorescence analysis.

RESULTSHep-3B cells were sensitive to BTV-HbC3. Lots of early apoptotic cells were found by TUNEL staining. The laser scanning confocal microscopic examination showed characteristics of apoptosis, such as pyknotic nuclei, margination of nuclear chromatin and vacuolization of endoplasmic reticulumin in Hep-3B cells exposed to BTV-HbC3. The activity of caspase-3/7 was increased, but the activity changes of caspase-8 and caspase-9 were not found. A549 cells were sensitive to BTV-HbC3 too. But no apoptotic cells were observed by TUNEL staining. The results of laser scanning confocal microscopy showed marked vacuolization of endoplasmic reticulum, but chromatin margination was not found after A549 cells was exposed to BTV-HbC3. The activity of caspase-3/7 and caspase-9 was increased, but the activity of caspase-8 was not changed.

CONCLUSIONBTV-HbC3 induces apoptosis of Hep-3B tumor cells mainly through endoplasmic reticulum signal transduction pathway, and the features of cell death in A549 cells could be described as paraptosis.

Adenocarcinoma ; metabolism ; pathology ; virology ; Apoptosis ; Bluetongue virus ; pathogenicity ; physiology ; Carcinoma, Hepatocellular ; metabolism ; pathology ; virology ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Nucleus ; pathology ; Endoplasmic Reticulum ; pathology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; virology ; Lung Neoplasms ; metabolism ; pathology ; virology ; Oncolytic Viruses ; pathogenicity ; physiology ; Signal Transduction

OBJECTIVEThe aim of this study was to elucidate the role of EGFR expression and HPV infection and their relationship in the genesis and progression of cervical carcinoma.

METHODSThis analysis included 60 cases of cervical carcinoma, 40 cases of CIN and 30 cases of control group. Patients of cervical carcinoma group were all subjected to radical hysterectomy with bilateral pelvic lymphadenectomy in Tumour Hospital, Zhongshan University from 1997 to 2001. The FIGO stage was I a - II b. EGFR protein was stained by S-P immunohistochemistry, and HPV16/18 DNA was detected by PCR.

RESULTSThe moderate/ strong expression of EGFR was observed in 0, 42.5%, 76.7% of normal cervical epithelium, CIN and cervical tumor tissue, respectively, with a significant difference among them (P < 0.05). The infection of HPV16/18 was observed in 6.7%, 67.5%, 58.3% of normal cervical tissue, CIN and cervical tumors, respectively. The infection rate of CIN or cervical carcinoma was significantly higher than that in normal cervicaltissue (P = 0.000), but no statistically significant difference was observed between cervical carcinoma and CIN. The moderate/strong expression of EGFR demonstrated an association with the cervical invasion depth. The EGFR expression increased significantly as the invasion depth progressed from less than or equal to a half cervical stroma to deeper than that (89.2% vs. 56.5%, P = 0.004). The infection of HPV16/18 demonstrated a correlation with the cervical canal invasion. The infection increased significantly in the cases with cervical invasion than that in the cases without invasion (88.2% vs. 46.5%, P = 0.003). But no significant correlation was observed between EGFR and HPV. Neither EGFR nor HPV had a significant association with carcinoma prognosis.

CONCLUSIONEGFR and HPV demonstrate a significant correlation with genesis and progression of cervical carcinoma. In our study, neither EGFR nor HPV demonstrates a significant association with tumor prognosis, and no significant correlation is observed between EGFR and HPV.

Adenocarcinoma ; metabolism ; surgery ; virology ; Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; surgery ; virology ; Cervical Intraepithelial Neoplasia ; metabolism ; surgery ; virology ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; Middle Aged ; Papillomavirus Infections ; Receptor, Epidermal Growth Factor ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; surgery ; virology ; Young Adult

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