Normal Cervical Tissue Samples Research Articles

Expression of EZH2 gene in cervical squamous carcinoma and its clinicopathologic significance

Objective To study the expression of EZH2 gene in cervical squamous carcinoma and its clinicopathologic significance. Methods The expression of EZH2 mRNA was detected in 21 samples of normal cervical tissue, 27 samples of CIN tissue and 48 samples of cervical squamous carcinoma tissue by RT-PCR. And the relationship between EZH2 expression and the clinical pathological characteristic was analyzed. Results The level of EZH2 mRNA in cervical squamous carcinoma tissues (1.67±0.01) were significantly higher than that in the normal cervical tissues (0) and CIN tissues (0.36±0.02) (P ＜ 0.01).There was no correlation between EZH2 and ages (P ＞ 0.05), while the expression of EZH2 was highly correlated with histologic stage,clinical stage,muscular invasion depth and lymph node metastasis of cervical squamous carcinoma (P ＜ 0.01).Conclusion The over-expression of the EZH2mRNA may play an important role in the pathogenesis and progression of cervical squamous carcinoma, suggesting that EZH2 might be a new biomarker for diagnosing cervical squamous carcinoma. Key words: Gene,EZH2; Cervix uteri; Carcinoma,squamous cell; Eeverse transcriptase polymerase chain reaction

Candidates for Tumor Markers of Cervical Cancer Discovered by Proteomic Analysis

Cervical cancer is the second most common gynecological cancer among Korean women. While nationwide screening program has developed, the pathogenesis of cervical cancer is unknown. The aim of this study was to compare the protein expression profiles between cervical squamous carcinomas and normal cervical tissues in order to identify proteins that are related to the cancer. Three cervical cancer tissue samples and three normal cervical tissue samples were obtained and protein expression was compared and was identified in the samples with the use of matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). A total of 20 proteins that showed up-regulated expression in the cervical cancer tissue samples were selected and identified. Seven proteins were matched to allograft inflammatory factor 1 (AIF-1), actine-like protein 2 (ALP2), brain type fatty acid-binding protein (B-FABP), NCK adaptor protein 1 (NCK-1), islet cell autoantigen 1 (ICA69), cationic trypsinogen (PRSS1), and cyclin-dependent kinase 4 (CDK4), but the remaining 13 proteins were unidentifiable. After confirmation by RT-PCR, Western blotting and immunohistochemistry, we found that B-FABP, NCK-1, and CDK4 were related to the pathogenesis of cervical cancer. These proteins are suggested as candidates of new pathological tumor markers for cervical cancer.

Inhibin-α subunit in normal and malignant human cervical tissue and cervical cancer cell lines

Inhibins are dimeric glycoproteins composed of an α‑subunit and one of two possible β-subunits (βA or βB), with substantial roles in human reproduction and in endocrine-responsive tumours. Four normal cervical tissue samples together with 10 specimens of well-differentiated squamous cervical cancer and adenocarcinoma of the cervix were immunohistochemically analysed for the expression of the inhibin‑α subunit. Additionally, two cervical carcinoma cell lines (HeLa and CaSKi) were analysed with immunofluorescence and RT-PCR for the expression of the inhibin‑α subunit. We demonstrated for the first time an immunolabelling of the inhibin‑α subunit in normal and malignant cervical tissue, as well as cervical cancer cells. However, the immunoreactive reaction was albeit weak and mostly confined to mitotic cells in the analysed cervical tissues. Additionally, the expression pattern of this subunit was rather inconsistent. Therefore, the immunohistochemical evaluation of this subunit in cervical tissue cannot be used as a prognostic marker as suggested for endometrial cancer. However, since the expression of the inhibin‑α subunit is minimal in HeLa cells as assessed by immunofluorescence and RT-PCR, the CaSKi cell line might be a better model for further functional experiments regarding cervical pathogenesis.

Reduced expression of PHD2 prolyl hydroxylase gene in primary advanced uterine cervical carcinoma

Decreased PHD2 expression in human carcinomas has been considered a critical factor in supporting tumor angiogenesis and growth. We studied the levels of PHD2 transcript and protein in advanced cervical cancer specimens (n = 27) and normal uterine cervical tissue samples ( n = 27). Real-time quantitative PCR and Western blotting analysis showed significantly lower levels of PHD2 transcript ( P = 0.0088) and protein ( P = 0.0095) in cancerous tissues as compared to corresponding normal tissue. Using DNA sequencing analysis, we also found an accumulation of mutations in promoter regions of PHD2 in advanced cervical cancer specimens. Moreover, computer analysis of these mutations showed a loss of binding sites for many transcription factors. Our results suggest PHD2 as a possible target in anti-angiogenic therapies in advanced uterine cervical carcinoma.

Immunolabelling of the inhibin/activin-βC subunit in normal and malignant human uterine cervical tissue and cervical cancer cell lines

Inhibins are dimeric glycoproteins, composed of an α-subunit and one of two possible β-subunits (βA or βB), with substantial roles in human reproduction and in endocrine-responsive tumours. Recently a novel β subunit named βC was described, although it is still unclear if normal or cancerous cervical epithelial cells as well as cervical cancer cell lines can synthesise the inhibin-βC subunit. Four normal cervical tissue samples together with specimens of well-differentiated squamous cervical cancer and adenocarcinoma of the cervix were immunohistochemically analyzed. Additionally, two cervical carcinoma cell lines (HeLa and CaSKi) were analyzed by immunofluorescence for the expression of this novel subunit. We demonstrated for the first time an immunolabelling of the inhibin-βC subunit in normal and malignant cervical tissue, as well as cervical cancer cells. Although the physiological role is still unclear in cervical tissue, the inhibin-βC subunit might play important roles in carcinogenesis. Moreover, the synthesis of this subunit in cervical carcinoma cell lines of squamous and epithelial origins allows the use of these cell lines in elucidating its functions in cervical pathogenesis.

Inhibin-betaA and -betaB subunits in normal and malignant glandular epithelium of uterine cervix and HeLa cervical cancer cell line

Inhibins, dimeric peptide hormones composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB), exhibit substantial roles in human reproduction and in endocrine-responsive tumors. However, it is still unclear if normal and cancerous cervical glandular epithelial cells as well as cervical cancer cell lines of glandular origin express the inhibin-betaA and -betaB subunits. Normal cervical tissue samples and a total of 10 specimens of well-differentiated adenocarcinomas of the human cervix were analyzed for inhibin-betaA and -betaB subunit expression by immunohistochemical analysis. Additionally, the cervical carcinoma cell line HeLa was analyzed by immunofluorescence and RT-PCR analysis for the expression of inhibin subunits. Immunolabeling of normal and malignant glandular epithelium of human cervical tissue revealed a positive staining reaction for the inhibin-betaA and -betaB subunits. Additionally, the cancer cell line HeLa synthesized both inhibin subunits. When compared to the normal cervical glandular epithelium, the expression of the inhibin beta subunits became significantly reduced in cervical adenocarcinoma tissues. In conclusion, we demonstrated a strong, though differential expression pattern of inhibin-betaA and -betaB subunits in normal and malignant glandular epithelial cells of the human uterine cervix. Although the physiological role of inhibins is still quite unclear in cervical tissue, the expression of inhibin-beta-subunits might play an important role in cervical cancer carcinogenesis, since they are significantly down-regulated during pathogenesis in cervical adenocarcinomas.

Expression and clinicopathological significance of human growth and transformation‐dependent protein (HGTD‐P) in uterine cervical cancer

Expression and clinicopathological significance of human growth and transformation‐dependent protein (HGTD‐P) in uterine cervical cancer

Abstract 319: Isoform-specific induction of MAPK p38 in cervical cancer

Abstract Cancer of the uterine cervix is the second most common female malignancy worldwide, with higher incidence occurring in developing countries. An expected 11,000 total new diagnosed cases in 2009 was reported by the American Cancer Society (Cancer Facts and Figures, 2009). Human papilloma virus (HPV) infection is considered the main causative agent for cervical cancer. Because of HPV infection, inflammation is persistent in cervical cancer and contributes to disease establishment and progression. Our previous studies have shown that inflammatory factors, like Cox2, tumor associated macrophages, and cytokines such as macrophage colony-stimulating factor (CSF-1) are elevated in cervical carcinomas. The receptor for CSF-1, encoded by the c-fms oncogene, was also elevated in cervical carcinomas compared normal cervical tissue. We have demonstrated that the transforming growth factor beta (TGF-beta), whose signaling is altered in cervical cancer, induced the expression of c-fms in cervical cancer cell lines via the activation of the c-fms trophoblast-specific promoter. In addition, TGF-beta induced the expression of c-fms in the macrophage cell line THP-1. The induction of c-fms by TGF-beta was diminished by the addition of the TGF-beta receptor 1 (A 83-01) and MAPK p38 (SB203580) inhibitors, implicating TGF-beta signaling and the p38 pathway in the regulation of c-fms expression. Four p38 isoforms encoded by distinct genes (p38α, β, γ and δ) have been identified, with more common expression observed for p38α and β and tissue-selective expression for p38γ and δ. Because SB203580 is a specific inhibitor for p38α and β but not p38γ or δ, inhibition of c-fms expression by this p38 antagonist implicated p38α and/or β in the regulation of c-fms. As p38 is a central signaling molecule in inflammation and regulation of leukocyte functions, both of which implicated in cervical carcinogenesis, our objective in this study was to examine the role of p38 in cervical carcinogenesis. We detected mRNA expression of all p38 isoforms in cervical cancer cell lines, human normal cervical tissue and cervical carcinoma samples. Protein expression of the p38 isoforms was confirmed in the cervical cancer cell lines HT-3, HeLa and CaSki. This suggested that the p38 isoforms may play distinct roles in cervical carcinogenesis. With the exception of p38α, which showed decreased expression in cervical carcinoma samples, p38β, γ, and δ showed increased expression in human cervical carcinomas compared to normal cervical tissue. The data suggest that elevated expression of p38β, γ, and δ in cervical carcinomas may play a role in cervical carcinogenesis. Thus, further studies are required to examine the specific roles of the p38 isoforms in cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 319.

Expression of VEGF VEGF-C and VEGFR-2 in in situ and invasive SCC of cervix

Cervical squamous cell carcinoma (SCC) arises from the metaplastic epithelium and develops slowly through dysplastic changes (i.e., cervical intraepithelial neoplasia--CIN) to carcinoma in situ and invasive cancer. There is little data concerning the quantitation of vascular endothelial growth factor (VEGF) and its correlation to the clinical or pathologic characteristics of SCC. This study assessed the expression of VEGF, VEGF-C and their receptor VEGFR-2 in 35 samples of normal cervical tissue, 35--CIN1, 35--CIN2 (25 non-pregnant, 15 pregnant women), 35--CIN3 and 30- SCC. VEGF, VEGF-C and VEGFR-2 were analyzed using RT-PCR, RQ-PCR, immunohistochemical staining and Western blot. VEGF, VEGF-C and VEGFR-2 were not detected in normal cervical epithelium. In CIN and SCC, both forms of VEGF and its receptor were identified, indicating a correlation between the increasing expression and staging of carcinoma. Results show the important role of VEGF in cervical progression and that the switch to the lymphangiogenesis phenotype occurs prior to the stage of invasion likely at CIN2/3.

Inhibin/activin-betaE subunit in normal and malignant human cervical tissue and cervical cancer cell lines

Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB), with substantial roles in human reproduction and in endocrine-responsive tumours. Recently a novel beta subunit named betaE was described, although it is still unclear if normal or cancerous cervical epithelial cells as well as cervical cancer cell lines can synthesise the novel inhibin-betaE subunit. About 4 normal cervical tissue samples together with 10 specimens of well-differentiated squamous cervical cancer and adenocarcinoma of the cervix were immunohistochemical analyzed. Additionally, two cervical carcinoma cell lines (HeLa and CaSki) were analyzed by immunofluorescence and RT-PCR for the expression of this novel subunit. We demonstrated for the first time an immunolabelling of the inhibin-betaE subunit in normal and malignant cervical tissue, as well as cervical cancer cells. Although the physiological role is still quite unclear in cervical tissue, inhibin-betaE might play important roles in carcinogenesis. Moreover, the synthesis of this subunit in cervical carcinoma cell lines of squamous and glandular epithelial origins also allows the use of these cell lines in elucidating its functions in cervical cancer pathogenesis. However, since the expression of the inhibin-betaE is minimal in HeLa cells as assessed by immunofluorescence and RT-PCR, the CaSki cell line might be a better model for further functional experiments regarding cervical cancer pathogenesis.

Immunohistochemical expression of ubiquitin and telomerase in cervical cancer

Ubiquitin and telomerase immunohistochemical expression patterns in cervical cancer were compared with normal cervical tissue samples. Eighty-one cervical cancer cases and 22 normal exo-endocervical tissue were examined with polyclonal antibody for ubiquitin and 44G12 clone for telomerase using tissue microarrays. The results were interpreted using a semiquantitative scale The average age of patients was 50.67 years. The most frequent histological types were moderately differentiated epidermoid carcinoma (43.5%), according to the degree of differentiation, and endocervical adenocarcinoma (42.1%). Immunohistochemical findings were as follows: 98.7% of cervical cancers showed immunoexpression for ubiquitin and 52.6% for telomerase. Statistically significant differences were found in tumor immunoreactivity when compared with control tissue (p < 0.0007) for both biomarkers. There was no significant difference in biomarker expression at different histological types of tumors, although telomerase was less expressed in endocervical adenocarcinoma. Our findings confirm that abnormal immunoexpression pattern of ubiquitin and telomerase is common in HPV-positive cervical cancer, indicating the existence of an intense degradation of proteins, subsequent cellular immortalization and maintenance of the malignant phenotype.

Correlation of HIPK2 expression with HPV infection and apoptosis in cervical cancer

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

Transcriptional expression of survivin and its splice variants in cervical carcinomas

The objective of this study was to evaluate transcriptional expression of survivin and the two splice variants (survivin-2B and survivin-DeltaEx3) in cervical carcinomas. The gene expression levels of survivin and its splice variants in 11 human cervical carcinoma cell lines and 20 malignant and 12 normal cervical tissue samples were analyzed using quantitative reverse transcription-polymerase chain reaction analysis. Gene expression levels of survivin and survivin-DeltaEx3 in cell lines were higher than those in normal cervical tissues (P= 0.0193 and 0.0489). Transcript levels of survivin and survivin-DeltaEx3 in carcinoma tissues were also higher than those in normal controls (P= 0.0016 and 0.0011). Gene expression levels of survivin and survivin-DeltaEx3 in adenocarcinomas were statistically higher than those in squamous cell carcinomas (P= 0.0260 and 0.0487). There was no significant difference in survivin-2B gene expression between malignant and normal cervical samples or different histologic types. The ratios of survivin-2B/survivin and survivin-DeltaEx3/survivin in carcinoma tissues were higher than those in normal controls (P= 0.0288 and 0.0081). Interestingly, the ratio of survivin-2B/survivin was increased in the patients with higher stages and with pelvic lymph node metastasis (P= 0.0205 and 0.0437), respectively. We conclude that survivin and its splice variants might be involved in the pathogenesis and development of cervical carcinomas.

Alternative splicing variants of IRF-1 lacking exons 7, 8, and 9 in cervical cancer

The two previously identified major splice variants of interferon regulatory factor 1 (IRF-1) do not appear to affect IRF-1-mediated gene activation. We searched for additional splice variants and examined their effect on wild-type IRF-1. RT-PCR experiments using normal and malignant human cervical tissue samples revealed five variants lacking some combination of exons 7, 8, and 9; their expression levels were higher in the malignant samples. These variants had predicted deletions of the functional domain or truncated protein isoforms, had different transcriptional activities, and attenuated transcriptional activity of IRF-1. Unlike the cell cycle-dependent IRF-1 transcript, the splice variant mRNA levels remained consistent throughout the cell cycle. The variant proteins were more stable than the IRF-1 protein, which may explain the strong inhibition of IRF-1 transcription in the presence of relatively small quantities of the alternative transcripts. In conclusion, alternative splicing in exons 7, 8, and 9 is an important mechanism for negatively regulating IRF-1 in cervical cancer.

Induction of Aromatase Expression in Cervical Carcinomas: Effects of Endogenous Estrogen on Cervical Cancer Cell Proliferation

Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) infection in cervical carcinogenesis, and some studies have suggested that estrogen and HPV may play synergistic roles in cervical tumorigenesis. In this study, we report a novel finding that approximately 35% of cervical carcinomas tested (n = 19) express aromatase, the enzyme responsible for converting androgen to estrogen, the rate-limiting and final step in estrogen biosynthesis. On the other hand, no aromatase expression was detected in precancerous (n = 42) or normal cervical (n = 17) tissue samples. Increased aromatase was associated with increases in estrogen receptors (ER-alpha and ER-beta) and a decrease in progesterone receptor levels, suggesting that in situ estrogen signaling via ER may be involved in tumor growth. Stable overexpression of aromatase in HPV+ cervical cancer cells resulted in increased cellular proliferation, anchorage-independent growth, and ER expression and activity. In contrast, little change in ER was observed in HPV- cells. Steroid hormone receptor expression observed in vitro paralleled that seen in cervical carcinomas expressing aromatase. Aromatase overexpression also induced the expression of cyclin D1, proliferating cell nuclear antigen, and the HPV oncogenes, E6 and E7. Furthermore, the data underscores the importance of steroid receptor (estrogen and progesterone receptors) regulation in cervical carcinogenesis. To our knowledge, this is the first report demonstrating the induction of aromatase expression in cervical carcinomas, and opens the possibility that aromatase inhibitors may be potential therapeutic agents in cervical carcinomas expressing aromatase.

SMAC is expressed de novoin a subset of cervical cancer tumors

BackgroundSmac/Diablo is a recently identified protein that is released from mitochondria after apoptotic stimuli. It binds IAPs, allowing caspase activation and cell death. In view of its activity it might participate in carcinogenesis. In the present study, we analyzed Smac expression in a panel of cervical cancer patients.MethodsWe performed semi quantitative RT-PCR on 41 cervical tumor and 6 normal tissue samples. The study included 8 stage I cases; 16 stage II; 17 stage III; and a control group of 6 samples of normal cervical squamous epithelial tissue.ResultsSmac mRNA expression was below the detection limit in the normal cervical tissue samples. In contrast, 13 (31.7%) of the 41 cervical cancer biopsies showed detectable levels of this transcript. The samples expressing Smac were distributed equally among the stages (5 in stage I, 4 in stage II and 4 in stage III) with similar expression levels. We found no correlation between the presence of Smac mRNA and histology, menopause, WHO stage or disease status.ConclusionsSmac is expressed de novo in a subset of cervical cancer patients, reflecting a possible heterogeneity in the pathways leading to cervical cancer. There was no correlation with any clinical variable.

Enhanced expression of α 2,6-sialyltransferase ST6Gal I in cervical squamous cell carcinoma

Objective Increased messenger ribonucleic acid (mRNA) expression of β-galactoside α 2,6-sialyltransferase I (ST6Gal I) is important in squamous cell carcinoma (SCC) of the cervix. In many tissues, ST6Gal I is transcriptionally regulated through the use of promoters that originate in the mRNA species that diverge in the 5′-untranslated regions. To clarify the roles of ST6Gal I mRNA species in cervical SCC, we investigated their expression, including a “constitutive” promoter (placental or Y + Z form), “hepatic” promoter (H form), and a specific lymphoblastic promoter (X form), in normal and SCC tissues of the cervix using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR). Methods Expression of the ST6Gal I species was investigated in normal cervical tissue samples ( n = 38) and FIGO IB1 cervical SCC samples ( n = 38) by relatively quantitative real-time RT-PCR, using primers designed for amplification of a portion of the coding region common to all mRNA species or ones for amplification of the placental transcript, the hepatic transcript, or lymphoblastic transcript. Results ST6Gal I mRNA expression was significantly increased in cancerous tissues compared to that in normal tissues ( P = 0.004, Mann–Whitney U test; P < 0.001, paired t test). Expression of the Y + Z form did not appear to be affected by cancer transformation, since it was detected at comparable levels in normal and cancerous tissues ( P = 0.986), but H form expression was significantly enhanced in cancerous tissues compared to that in normal tissues ( P < 0.001, Mann–Whitney U test and paired t test). Surprisingly, the X form could be detected in some patients with and without cancer, but the detection rate was significantly higher in patients with cancer (86.8% vs 52.6%, respectively; P = 0.021, Fisher’s exact test). Although the X transcript was detected at a low level compared to the H and Y + Z transcripts, its expression was also significantly enhanced in patients with cancers compared to those without cancers ( P < 0.001, Mann–Whitney U test and paired t test). Conclusions An increased level of hepatic transcripts may be important in cancer transformation because the transcripts contribute to enhance ST6Gal I expression in cancerous tissues.

P16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep™ smears

Aim: To examine the potential of p16INK4A as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and ThinPrep™ smears. Methods: Immunocytochemical analysis of p16INK4A...

Effect of Acetic Acid on Telomerase Activity in Cervical Intraepithelial Neoplasia

Objective.To evaluate whether the telomerase activity in CIN lesions can be affected by a chemical solution of acetic acid, which is required to apply to the cervix prior to colposcopy-directed biopsy.Materials and methods.Thirty-five patients with histologically confirmed high-grade squamous intraepithelial lesions of the cervix entered the study. Two specimens were collected from each patient, one before and one after the cervix was swabbed with 5% acetic acid. The standard telomeric repeat assay protocol (TRAP) was used to examine telomerase activity in these fresh frozen tissue samples. Normal cervical tissues from 10 control individuals were also examined for the presence of telomerase activity. A total of 80 specimens was analyzed.Results.Telomerase activity was detectable in 27 of 35 (77.1%) fresh tissue samples, 15 of 35 (42.9%) tissue samples swabbed with 5% acetic acid, and 0 of 10 (0%) normal cervical tissue samples, respectively. Twelve samples became telomerase negative after 5% acetic acid applied. Among the 15 telomerase-positive tissue samples swabbed with 5% acetic acid, 12 had relative weak telomerase activity compared to corresponding fresh tissue samples, the other 3 remained the same. Therefore, it is concluded that telomerase activity was affected by 5% acetic acid in 24 of 27 (88.9%) samples. Telomerase activity in HeLa cell line was also inhibited by 5% acetic acid.Conclusion.We reported a relative high percentage of telomerase expression in high-grade CIN lesions when compared with previous reports. If detection of telomerase activity is to become a tool for diagnosis and prognosis of cervical neoplasias, applying acetic acid prior to colposcopy-directed biopsy that is submitted for telomerase assay should be avoided in order to increase the detection rate.

EXPRESSION OF NM23-H1 GENE IN SQUAMOUS-CELL CARCINOMA OF THE CERVIX CORRELATES WITH 5-YEAR SURVIVAL

We have examined nm23-H1 protein levels in human squamous cell carcinoma of the cervix by immunohistochemistry and correlated detectable nm23-H1 with patient survival. Normal cervical tissue samples were consistently strongly immunoreactive. In contrast, cervical carcinomas stained poorly, if at all. Well differentiated carcinomas stained more frequently for nm23-H1 protein than poorly or undifferentiated carcinomas. Our results clearly demonstrated a significant correlation between absence of nm23-H1 protein staining and shorter survival of patients with cervical cancer. Our results suggest that nm23 may serve as a potentially valuable prognostic marker for this type of tumor and to our knowledge is the first report of this kind for cervical carcinoma.