THE INFECTION OF EBV FOR CERVICAL EPITHELIUM-A NEW CAUSITIVE AGENT IN THE DEVELOPMENT OF CERVICAL CARCINOMAS?

Epstein-Barr virus was considered as a caustive agent for Burrkitt' s lymphoma and non-malignant B lymphocytes proliferation. The recent studies revealed the striking association of the Infection of EBV with the development of human epithelial tumors. 43 specimens of normal exfoliated cervical epithelial cells, 47 biopsies of chronic cervlcitis and 80 tissue samples of cervical carcinomas were tested for the presences of EBV W fragments by using dot blot hybridization method. The results showed that the detectable rates of EBV DNA sequences In the normal exfoliated epithelium, the chronic cervlcitis and cervical carcinomas were 44.16%, 12.77% and 13.75%, respectively. Eleven EBV positive DNA samples from cervical cancers were also examined for the presence of HPV DNA. The result showed 9 out of 11 were HPV DNA positive, the cultanious infectious rate of both viruses was about 81.81%.In this paper, the EBV genomes existed In the part of biopsies of cervical carcinomas were first reported. The results Implied that the development of cervical cancer might be associated with asymptomatic EBV Infection In early stage and might be the result from the synergistic carcinogenesis of EBV with other cervical oncovinises, especially with HPV.

A PRELIMINARY STUDY ON SURVIVIN AND BCL-2 EXPRESSION IN CERVICAL CARCINOMAS

Objective To study the expression of a novel inhibitor of apptosis and survivin in cervical carcinoma and its relationship to the expression of Bcl-2.Methods Using SP immunohistochemical technique, we examined the expression of survivin and Bcl 2 in 59 cervical invasive squamous cell carcinomas.Results Survivin was expressed in 41 of 59 cases(69.5%) of cervical carcinomas. In contrast, no expression of survivin in normal cervical tissues was observed. Overexpression of survivin was related to the tumor grade and clinical stage. Survivin positive cases were strongly associated with Bcl 2 expression(80% versus 35.7%; P <0.005).Conclusion Apoptosis inhibition by survivin abnormal expression, alone or in cooperation with Bcl 2, may participate in the onset and progression of cervical carcinoma. Survivin is a new diagnostic/therapeutic target in cervical cancer.

Detection of Human Papillomavirus Type 16 DNA in Cervical Carcinomas

Accurate typing of the different human papillomavirus types is csscntial in view of the differ-ent pathological potential of the common virus types of human papillomavirus （HPV） present in thecervix. We have developed hybridization, washing and autoradiography conditions that minimize thecross-hybridization among different specific types of HPV so as to allow clear - cut type assignmentthrough practical dot blot hybridization technique using nylon membrane and 35S - labeled HPV - 16DNA probe. Under these conditions seventeen of thirty （56.7%） of squamous cell carcinomas of thecervix uteri obtained from Tianjin women were detected in the presence of HPV - 16 DNA.

Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Mechanisms of Sophora flavescens in the treatment of cervical squamous cell carcinoma based on comprehensive biological analysis,network pharmacology,and experimental verification

Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Methods:Consistently altered genes involved in cervical squamous cell cancerization were analyzed in the GEO database.The chemical ingredients and target genes of Sophora flavescens were explored using the TCMSP database.We obtained the potential therapeutic targets of Sophora flavescens by intersecting the above genesets and validated them in the GEPIA database.The interaction between Sophora flavescens and target genes was predicted by molecular docking.RT-qPCR was used to verify the changes of target genes in HeLa cells treated with Sophora flavescens.Single-gene GSEA functional analysis were performed to determine the molecular mechanisms.Results:Fifteen genes related to the transformation of cervical squamous cell carcinoma were identified,among which AR and ESR1 were confirmed as targets for kaempferol,wighteone,formononetin,and phaseolinon.These compounds are the active ingredients in Sophora flavescens.Low expressions of AR and ESR1 correlate with a poor prognosis,while Sophora flavescens treatment increases the expression of AR and ESR1 in HeLa.GSEA analysis showed that AR and ESR1 mainly participate in the epithelial-mesenchymal transition in cervical squamous cell carcinoma.Conclusion:Sophora flavescens exert anti-tumor effects by targeting AR and ESR1,which may regulate cancer metastasis.

THE CERVIX MULTI－VIRUSES INFECTION AND THE DEVELOPMENT OF CERVICAL CARCINOMAS

The infections of human papilloma virus (HPV),herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) to human cervical epithelium are universal and some of them are associated with the development of cervical carcinomas. One hundred and eleven cervical cancer biopsies taken from Beijing area and Xiangyuan county in Shanxi province of China were examined for the presence of DNA sequences of HPV, HSV-2 and EBV by means of Dot blot hybridization. The experiment results showed that the total infectious rates of HPV, HSV-2 and EBV were 71.17% (79/111), 14.44%(16/111) and 15.63% (15/96), respectively. Seventy-nine samples positive for HPV were further analysed for the viral types distribution, the result indicated that the positive specimens of HPV type 16 accounted for 72.15%, otherwise, the biopsies positive for HPV type 18and 6B/11 only accounted for 16-46% and 11.39%,respectively. The data suggested that HPV infection,especially HPV type 16, may play an important role in the development of cervical carcinomas- 16 specimens positive for HSV-2 were examined for HPV DNAsequences and the result uncovered that 13 out of them were HPV16 positive (81.25%), 11 samples containing EBV genomes were also examined for HPV DNA sequences and the result indicated that 9 of 11 were detectable for HPV DNA. The experiment results proved a direct evtidence of multi-virus infection in cervix and of the synergistic interaction among viruses in the process of cervical epithelial carcinogenesis.Comparing of the viruses' infection of two areas, the frequencies of HPV infection in Beijing and Xiangyuan areas were 72.84% (59/ 81) and 66.67% (20/30) , the infectious rates of HSV-2 in the two areas were 8.64%(7/81) and 30% (9/30) (P<0.05), the rates of EBV infection in the two areas were 12.5% (10/80) and 31.25% (5/16)(0.1>P>0.05). The results proved another strong evidence that the high incidence of cervical cancer in Xiangyuan county may be closely correlated with multiviruses infection and with multi-virus synergistic interaction.

THE OVEREXPRESSION AND SIGNIFICANCE OF CYCLIN D1 AND P53 IN CERVICAL SQUAMOUS CELL CARCINOMAS

Objective To investigate the significance of overexpresson of cyclin D1 and P53 protein in cervical squamous cell carcinomas.Methods Fifty cases of invasive cervical squamous cell carcinomas and 10 cases of normal cervical squamous epithelia were investigated with immunihistochemical technique. Results The overexpression of cyclin D1 and P53 in invasive cervical carcinomas was 70% and 50%, respectively. There was no overexpression of them in the control group. The overexpression of cyclin D1 in grade Ⅱ and Ⅲ was much higher than that in gradeⅠ(P<0.05). The overexpresson of cyclin D1 in stage Ⅲ of cervical carcinoma was significantly higher than that in stage Ⅱ (P<0.05). The overexpression of P53 in grade Ⅱ and grade Ⅲ of cervical carcinoma was remarkably higher than that in grade Ⅰ (P<0.05).Conclusion The action point of both cyclin D1 and P53 may be at G1/S transition. The overexpression of them was associated with development and progression of cervical carcinoma probably in different mechanisms and different pathways.

Inhibiting PI3K/Akt Pathway Increases DNA Damage of Cervical Carcinoma HeLa Cells by Drug Radiosensitization

This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuclear cell direct cytotoxicity assay(MTT) in vitro.HeLa cells were treated by cisplatin/docetaxel of 10 percent of IC20 alone or combined with LY294002 for 24 h,and then radiated by different doses of X-ray.The cell survival ratio was obtained by means of clone formation.One-hit multi-target model was fitted to the cell survival curve to calculate dose quasithreshold(Dq),mean lethal dose(D0),2Gy survival fraction(SF2) and sensitization enhancement ratio(SER).The pAkt and total Akt expression was detected by Western blotting and DNA damage by neutro-comet electrophoresis.The HeLa cells were randomly divided into 7 groups in terms of different treatments:Control;radiation treatment(RT) group;LY294002+RT group;cisplatin+RT group;docetaxel+RT group;LY294002+cisplatin+RT group;LY294002+docetaxel+RT group.The apoptosis ratio of each group was measured by flow cytometry.The results showed that docetaxel and cisplatin significantly enhanced the phosphorylation of Akt in radiation-treated HeLa cells.The Dq,D0 and SF2 in LY294002-contained groups were lower than those in docetaxel or cisplatin+RT group.The SER in the LY294002+docetaxel+RT group was 1.35 times that of the docetaxel+RT group,and that in the LY294002+cisplatin+RT group 1.26 times that of the cisplatin+RT group.The Comet electrophoresis showed that tail distance in the LY294002+cisplatin+RT group or LY294002+docetaxel+RT group was longer than in the cisplatin+RT group or docetaxel+RT group.The apoptosis ratio in the LY294002+cisplatin+RT group or LY294002+docetaxel +RT group was higher than in the cisplatin+RT group or docetaxel+RT group.It was concluded that inhibiting PI3K/Akt pathway can increase the effect of docetaxel and cisplatin on the radiosensitivity of HeLa cells and DNA damage resulted from radiation.

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,respectively.The results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect relationship.The results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean survival.Experimental results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

EFFECTS OF CURCUMIN ON PROLIFERATION AND APOPTOSIS OF HUMAN CERVICAL CARCINOMA HeLa CELLS IN VITRO

Objective: To investigate the regulatory effect of curcumin on proliferation and apoptosis in human cervical carcinoma cell line HeLa in vitro. Methods: Human cervical carcinoma cell line Hela was cultured in vitro. HeLa cells were treated with 10~50 mmol/L curcumin for 24~72 h and the growth inhibition rates of HeLa cells were measured by MTT method. Cell apoptosis was inspected by electron microscopy. In addition, the expression of bcl-2, bcl-xl and caspase-3 protein in HeLa cell were observed by SP immunohistochemistry. Results: Curcumin inhibited the proliferation of HeLa cells on a dose-depending manner. Peak of subG1 appeared on DNA histogram in FCM. A portion of the cells presented the characteristic morphological changes of apoptosis under the electron microscope. The bcl-2, bcl-xl expression was decreased while Caspase-3 expression was increased. Conclusion: Curcumin could significantly inhibit the growth of HeLa cells; inducing apoptosis through up-regulating Caspase-3 and down-regulating expression of bcl-2 and bcl-xl was probably one of its molecular mechanisms.

Expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics

Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.

Coexistence of cervical extramedullary plasmacytoma and squamous cell carcinoma:A case report

BACKGROUND Extramedullary plasmacytoma(EMP),a variant form of myeloma,is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3%of all plasma cell tumors.EMP can affect various tissues and organs,about 90%of which is found in the head and neck.However,EMP in the reproductive organs is rare,and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings.CASE SUMMARY Herein,we report a case with coexistence of EMP and squamous cell carcinoma in the cervix.The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP.Both ultrasound and pelvic enhanced magnetic resonance imaging(MRI)indicated that there was a tumor in the cervix.Thus,another cervical biopsy and pathological examination were performed,which indicated EMP combined with squamous cell carcinoma.Then,the patient underwent extensive total hysterectomy(type C1)+systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery.During 2-year follow-up,no recurrence was reported.CONCLUSION In conclusion,EMP involving the reproductive system is relatively rare.In this case,MRI,B-ultrasound,and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma.The patient had improved prognosis after appropriate treatments.

VARIATION ANALYSIS OF HPV16 CELL-TYPE-SPECIFIC ENHANCER IN CERVICAL CARCINOMA

Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41%(14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.

Relationship between Microsatellite Alterations of RASSF1A Gene and Development of Cervical Carcinoma

Objective： To explore the relationship between microsatellite alterations of RASSFIA gene and the development of cervical carcinoma, and its relationship with HPV16 infection. Methods： Two sites of microsatellite polymorphism of RASSFIA gene were selected. Polymerase chain reaction （PCR） technique was used to detect LOH and MSI in 50 cases of cervical carcinoma and 40 cases of cervical intraepithelial neoplasia （CIN）, and to detect the infection state of HPV16. Results： At D3S1478 and D3S4604, the LOH rates of cervical carcinomas were 32.6% （14/43） and 48.9% （23/47）, the MSI rates were 14% （6/43） and 19.1% （9/47）, respectively. The LOH rates of CINs were 31.4% （11/35） and 39.5% （15/38）, the MSI rates were 11.4% （4/35） and 15.8% （6/38）, respectively. There were no significant differences between cervical carcinomas and CINs in respect to their positive rates of LOH and MSI at D3S1478 and D3S4604 （P〉0.05）. There were significant differences in LOH rates at D3S1478 and D3S4604 between the stage Ⅰ-Ⅱ and Ⅲ-Ⅳ cervical carcinomas and between the well/moderately differentiated cervical carcinomas and the poorly differentiated cervical carcinomas （P〈0.05）. The positive rates of LOH and MSI for CIN Ⅲ and noninvasive cervical carcinomas were higher than those in CIN Ⅰ-Ⅱ. The rates of infection of HPV16 in cervical cancer was obviously higher than that in CIN and in normal cervical tissues （P〈0.05）, and the incidence of LOH of RASSFIA gene was higher in HPV16（＋） than that in HPV16（-） （P〈0.05）. Conclusion： The RASSFIA gene change is a relatively late event in cervical carcinomas. The detection of LOH and MSI of RASSFIA gene might be helpful to the early diagnosis and the screening of cervical carcinoma. It might also be useful for predicting the prognosis of cervical carcinoma.

Risk Factors of Cervical Carcinoma and Countermeasures against Them in Mountainous Area of Wufeng County, China

Cases (n=44) with squamous cell cervical cancer (SCCA) and age-matched healthy controls (n=176) were analyzed. Significant difference due to human papillomavirus (HPV) infection, ages at the first marriage, ages at the first sexual intercourse, ages at the first birth given to baby, number of gravidities, number of deliveries, Body Mass Index (BMI), education level of women and their husbands (p<0.05) was observed. According to multivariate logistic regression analysis, four factors have entered the model (p<0.05), including HPV infection [OR (odds ratio)=26.13, 95%CI (confidence interval)=9.40?72.60], education level of women (OR=0.41, 95%CI=0.21?0.79), education level of spouses (OR=0.45, 95%CI=0.22?0.94), BMI (OR=0.73, 95%CI=0.57?0.93). Moreover, HPV infection is relative to education level of women (r=?0.14), and their spouses (r=?0.21), age at the first marriage (r=?0.20), age at the first birth given to baby (r=?0.20) and BMI (r=?0.15).

THE DIFFERENTIATION INDUCING EFFECT OF TANSHINONE AND RETINOIC ACID ON HUMAN CERVICAL CARCINOMA CELL LINE（ME180） IN VITRO

The cervical carcinoma cell line, ME180 cells were treated with tanshinone (Tan) or retinoic acid (RA) in DMSO (final concentration 0.02%, V/V) on 4 successive days. The cells treated with the same concentration of DMSO alone served as control. Morphological studies with light and transmission electron microscopy showed that the cells treated with both Tan and RA became welldifferentiated. The cellular growth and proliferation were suppressed (as revealed by cell counting. [3H]-thymidine uptake and colony-forming assay). The number of nuclear organizer regions(AgNORs) in cells reduced and the distribution type returned nearly to normal type. The tumorigenicity in nude mice was reduced. The cell RNA dot hybridization showed that the expression of c-myc and c-Ha-ras mRNA was inhibited markedly. All above results showed that Tan and RA could reverse some malignant Phenotype and possessed differentiation inducing activity on ME180 cell line. No significant difference was observed between the cells treated with Tan and RA.

Endu combined with concurrent chemotherapy and radiotherapy for stage IIB-IVA cervical squamous cell carcinoma patients

BACKGROUND In recent years,the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles,posing a serious threat to women's physical and mental health.AIM To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma.METHODS A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects.They were equally divided into the test group and the control group(60 patients each)with a random number table.The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy,and the control group was treated with concurrent radiotherapy and chemotherapy.We compared the serum thymidine kinase 1(TK1),human epididymis protein 4(HE4),vascular endothelial growth factor(VEGF),and squamous cell carcinoma-associated antigen(SCC-Ag)levels,the clinical effects and survival before and after radiotherapy and chemotherapy,the quality score,and the 3-year follow-up outcomes between the two groups.RESULTS After chemotherapy,the complete remission+partial remission rate was 85.00%in the test group and 68.33%in the control group;the difference was not statistically significant(P>0.05).Before chemotherapy,the serum TK1,HE4,VEGF,and SCC-Ag levels of the two groups were not significantly different(P>0.05).After chemotherapy,the levels of serum TK1(1.27±0.40 pmol/L),HE4(81.4±24.0 pmol/L),VEGF(235.1±38.0 pg/mL),and SCC-Ag(1.76±0.55 ng/mL)were lower than those in the control group[TK1(1.58±0.51 pmol/L),HE4(98.0±28.6)pmol/L,VEGF(284.2±54.1 pg/mL),and SCC-Ag(2.34±0.78 ng/mL)].The difference was statistically significant(P<0.05).Before chemotherapy,there were no significant differences in the physical,role,mood,cognition,social and symptom scale scores of the two groups(P>0.05).After chemotherapy,the physical,role,mood,cognitive and social scores were higher in the test group than in the control group,and the difference was statistically significant(P<0.05).The symptom scale scores of the test group were all lower than those of the control group,and the difference was statistically significant(P<0.05).The 3-year progression-free survival(PFS)rate was 43.33%in the test group and 26.67%in the control group;the overall survival(OS)rate was 48.33%in the test group and 33.33%in the control group;the differences were not statistically significant(P>0.05).The 3-year PFS time of the test group was 20.0 mo,which was longer than that of the control group(15.0 mo),and the difference was significant(P<0.05).The OS time of the test group was 30.0 mo,which was longer than that of the control group(18.0 mo),and the difference was significant(P<0.05).CONCLUSION Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients,prolonging the PFS and OS times of patients,and improving the quality of life.

THE RELATIONSHIP BETWEEN THE INVASION OF PARAPHARYNGEAL SPACES AND THE INVOLVEMENT OF CERVICAL NODES AND POSTERIOR GROUP CRANIAL NERVES IN NASOPHARYNGEAL CARCINOMA

Two hundred cates of nasopharyngeal carcinoma (NPC) admitted to this department from Feb. 1985 to May. 1988 were analysed according to the CT scanning and clinical findings of the primary lesions prior to radiotherapy. The results showed that involvement of parapharyngeal space was very common in NPC, about 80% (160/200 cases) ; particularly unilateral or bilateral retro-styloid spaces, about 69.5% (139/200 cases). It was proposed that patients with NPC had a high Incidence of ipsilateral cervical node metastasis. Contralateral cervical node metastasis was rare. The development of cervical node metastasto in NPC has two modes: one Is direct Infiltration of the retro-stylold space by the lesion; the other Is along the nasopharyngeal lymphatic rete. The data also showed that patients with NPC who presented symptoms of Ⅸ- Ⅲ cranial nerve paralyses always had ipsilateral or bilateral retro- styloid space Infiltrations.

PROGNOSTIC FACTORS IN CERVICAL CARCINOMA

Objective: To evaluate factors for prognosis of cervical carcinoma. Methods: Expressions of mn23- HI, erbB3 and erbB4 were examined by immunohistochemical staining. The apoptosis was detected in situ by the TdT mediated duip-biotin nick end-labeling (TUNEL) technique. Mitotic cell were counted by HE dyeing. Results: FIGO stage and lymph node metastasis were the most important factors for evaluating prognosis in adenocarcinoma or squamous cell carcinoma. AI/MI was positively correlated with 5-year survival of cervical carcinoma. Positive expression of nm23-H1 combed with negative expression of erbB4 [nm23-H1(+)/erbB4(?)] predicted good prognosis for adenocarcinoma. In multivariable Cox regression analysis, only FIGO stage and AI/MI were into equation. Conclusion: FIGO stage and AI/MI were independent evaluating parameter for adenocarcinoma or squamous cell carcinoma.

GENETIC INSTABILITY IN CERVICAL CARCINOMA

Objective: The role of human papillomavirus (HPV) in the development of cervical carcinoma has been clearly established but other factors could be involved in cervical tumorigenesis such as loss of heterozygosity (LOH) and microsatellite instability (MI). The aim of the present study was to investigate the genetic instability in cervical carcinoma tissues and provide evidence for discovering new tumor suppressor genes and screening diagnostic molecular marker of cervical carcinoma. Methods: Fifty primary cervical carcinoma samples from high-incidence area were analyzed by PCR for HPV16 infection, LOH and microsatellite instability. Results: HPV16 was detected in 88% of the cases. Sixty-six percent of total cases showed LOH with no more than 3 different loci per case. The highest frequency of the allelic loss was found in D18S474 (18q21, 40.5%). MI was detected in 4 cases (8%) only. Conclusion: Different percentages of LOH on specific chromosomal regions were found and MI was very infrequent in cervical carcinoma. The putative suppressor gene(s) could be located on specific chromosome regions such as 18q, and genetic instability could be involved in cervical tumorigenesis.