Biomedical subjects

G G Kenter

Publications and source records attributed to G G Kenter.

At least 37 records · Page 2Linked to original sources

PubMed2000

The case for completing the lymphadenectomy when positive lymph nodes are found during radical hysterectomy for cervical carcinoma.

BACKGROUND: In the present study we report on the results of a retrospective study on the effect on survival of the pelvic lymphadenectomy in a group of 294 patients with stage Ia2-IIa cervical carcinoma treated by radical hysterectomy from 1984 through 1996 at the Leiden University Medical Center. METHODS: Lymphadenectomy was called 'complete' when lymph node bearing tissue had been removed from 5 or 6 lymph node stations and 'not-complete' when this was the case in 1-4 stations. RESULTS: A radical hysterectomy was carried out in 294 patients. In 63 patients positive lymph nodes were found. Patients with positive nodes showed poorer 5 year survival: 64.5% compared to 90% in patients with negative nodes. In the univariate analysis the following factors were found to affect the presence of node metastases in a statistically significant way: age, tumor size, depth of infiltration, vaso-invasion, surgical margins, parametrial infiltration, stage and place of referral. In 63 patients with positive nodes, a complete lymphadenectomy was carried out in 23 patients, and in 40 patients the procedure was incomplete. All 63 patients were treated by adjuvant radiation therapy; those with complete lymphadenectomy had significantly less recurrences (25%) compared to those with incomplete lymphadenectomy (56%): the relative risk (RR) was 2.9 (95% ci: 1.3-6.7), p=0.012. After adjustment for other prognostic factors including tumor size, depth of infiltration and parametrial involvement, the complete lymphadenectomy showed an independent effect on disease free survival: RR= 3.2 (95% ci: 1.3-7.7), p=0.011. Prognostic factors were not significantly different for patients with complete or incomplete lymphadenectomy. CONCLUSIONS: From the results of this study, although retrospective and non randomized, it can be concluded that to complete removal of lymph nodes in combination with radical hysterectomy seems to have a beneficial effect on prognosis in case of positive nodes. The policy of aborting the procedure when lymph node metastases are found in frozen section should be questioned.

Carcinoma↗

PubMed1999

Recurrent integration of human papillomaviruses 16, 45, and 67 near translocation breakpoints in new cervical cancer cell lines.

Progressive chromosomal changes and integration of human papillomavirus (HPV) sequences mark the development of invasive cervical cancer. Chromosomal localization of HPV integration is essential to the study of genomic regions involved in HPV-induced pathogenesis. Yet, the available information about HPV integration loci is still limited, especially with respect to different HPV types. We have established cell lines from five cervical cancers with HPV-16, HPV-45, and HPV-67. We have determined HPV integration sites and karyotype abnormalities by using the multicolor combined binary ratio-fluorescence in situ hybridization method (Tanke et al.) with 24 chromosome-specific paints in combination with full-length HPV DNA probes. All cell lines were cytogenetically abnormal, and exhibited numerical and structural chromosomal deviations. HPV sequences were integrated at various (segments of) chromosomes. Duplicate integration sites were seen in all multiploid cell lines, suggesting that viral integration had preceded chromosomal endoreduplication. HPV-16 was found near the t(3p14.1-14.3;14) breakpoint in cervical squamous cell carcinoma (CSCC)-7 and mainly in episomal form in CSCC-1. HPV-45 was integrated near 3q26-29 in cervical (adeno or adenosquamous) carcinoma (CC)-8 and near 1q21-23 as well as near the t(1q21;22q13) breakpoint in CC-10A and CC-10B variant lines. HPV-67 was localized near the breakpoint of t(3p23-26;13q22-31) in CC-11. Southern blot analysis showed that, except for CSCC-1, the physical state of HPV in the cell lines was the same as in the original tumor lesions. This set of six cervical cancer cell lines included three lines with HPV-45, a major non-Western high-risk HPV type, the first reported HPV-67-positive cell line, and two cell lines with integrated and episomal HPV-16 DNA, respectively. The novel combined binary ratio-fluorescence in situ hybridization technique enabled us to simultaneously map chromosomal rearrangements and HPV integration sites, thereby revealing recurrent integration near translocation junctions for all of these HPV types in the cell lines from three of the five primary tumors. The detection of multiple HPV integration sites at rearranged chromosomes at such high frequency in cervical cancer-derived cells may reflect events that are relevant to the development of cervical cancer.

Adult↗

PubMed1999

Identification of sentinel lymph nodes in vulvar carcinoma patients with the aid of a patent blue V injection: a multicenter study.

BACKGROUND: The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients. METHODS: In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue V was injected intradermally shortly before surgery. Routine groin lymph node dissection and radical vulvectomy were performed. During the surgery, blue lymph vessels and lymph nodes were identified, and the blue lymph nodes were sent separately for histologic examination. The negative predictive value of the blue lymph nodes for the absence of metastases was assessed by histologic examination of the groin lymph node specimens. RESULTS: Fifty-one patients in whom 93 groin lymph node dissections were performed were entered. One or more blue lymph nodes were detected in only 52 groins (56%). Nine (17%) of these were tumor positive, and 6 blue lymph nodes were the only tumor positive lymph nodes in the specimen in which they were found. There were two false-negative blue lymph nodes. The negative predictive value was 0.953. CONCLUSIONS: It was shown in this multicenter study that sentinel lymph node detection in vulvar carcinoma patients with blue dye only is not feasible because its negative predictive value is too low. Further studies involving the use of a combination of radioactive labeled technetium and blue dye are warranted.

Adult↗

PubMed1999

Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix.

Most cervical carcinomas appear to arise from cervical intraepithelial neoplasia (CIN) lesions. In addition to infection with high-risk human papilloma viruses, which is indicative of an increased risk of progression, alterations of oncogenes and tumor suppressor genes play a role. Genetic studies of CIN lesions, primary cervical carcinoma, and metastases may shed light on the relative importance of various genetic alterations involved in the progression of CIN to invasive carcinoma. We examined tumor material from 10 patients with squamous cell carcinoma of the uterine cervix and synchronous CIN lesions and lymph node metastases. The CIN component, invasive carcinoma, and lymph node metastases were analyzed separately for loss of heterozygosity (LOH) on the following loci: VHL (3p21), HLA region (6p22-23), PGL (11q 22-24), E6 associated protein (15q11-13), TP53 (17p13), DCC (18q21.1), and chromosomes 1, 2, 4, 9, 20, and X. Using immunohistochemistry, the expression of the EGF receptor, ERBB2, and TP53 was determined. In CIN lesions, frequent LOH was found at chromosome arms 3p, 6p, and 11q. Primary invasive carcinoma showed additional LOH at chromosome arms 6q, 17p, and 18q. In lymph node metastases, an additional locus on the X chromosome displayed LOH. All carcinomas and synchronous lesions but one showed high expression levels of the EGF receptor. TP53 staining, when present, was found in all synchronous lesions. Focal staining of ERBB2 was found in one CIN lesion, two invasive carcinomas, and four metastases. The molecular alterations accumulated in a fashion that paralleled the progression of the tumors. These results indicate that cervical tumorigenesis occurs in a stepwise fashion, including infection and integration of oncogenic HPV and several specific genetic alterations. Genes Chromosomes Cancer 26:346-354, 1999.

Adult↗

PubMed1999

HLA and susceptibility to cervical neoplasia.

The association between cervical neoplasia and certain HLA phenotypes observed in different studies has not been consistent. By serological typing, the association between HLA antigens, cervical carcinoma and cervical intraepithelial neoplasia (CIN) was studied in a group of 172 and 116 patients, respectively. We demonstrated an increased frequency of B63 in patients with HPV types other than HPV 16 or 18, and B55 in patients that were negative for all HPV types. The association between cervical carcinoma and DQ3, described in various populations, was not observed in the present study. However, we confirmed other previously observed associations between cervical cancer and class II antigens, i.e., a positive correlation with DR15 irrespective of the HPV status, with DR3 in patients harboring HPV types other than HPV 16 or 18, and with DR11 among HPV 16 positive patients. In contrast, a negative correlation between DR13 and HPV positive cervical cancer was observed which suggests protection of this antigen against HPV-associated cervical cancer. A slight increase of DR15 and DQ4 antigens was observed in CIN patients, suggesting that these specific HLA antigens may be important in determining the risk of CIN.

Carcinoma↗

PubMed1999

Immunotherapeutic strategies for cervical squamous carcinoma.

Progress in developing preventive and therapeutic vaccines for HPV-associated diseases has been made in the last few years, but continued studies are needed to evaluate the clinical feasibility of different vaccination approaches and to determine a clinically effective and safe one. The perfect HPV vaccine will have both preventive and therapeutic capabilities, and because it is likely to be used world-wide, especially in developing countries, it must also have low production costs.

Carcinoma, Squamous Cell↗

PubMed1999

Vaccination with HPV16 peptides of patients with advanced cervical carcinoma: clinical evaluation of a phase I-II trial.

A phase I-II clinical trial was performed involving vaccination with HPV16 E7 peptides of patients suffering from HPV16 positive cervical carcinoma which was refractory to conventional treatment. Patients receiving the vaccine were HLA-A*0201 positive with HPV16 positive cervical carcinoma. The clinical trial was designed as a dose-escalation study, in which successive groups of patients received 100 micrograms, 300 micrograms or 1000 micrograms of each peptide, respectively. The vaccine consisted of two HPV16 E7 peptides and one helper peptide emulsified in Montanide ISA 51 adjuvant. 19 patients were included in the study, no adverse side-effects were observed. 2 patients showed stable disease for 1 year after vaccination; 15 patients showed progressive disease of whom 1 died during the vaccination treatment due to progressive disease; and 2 patients showed tumour-regression after chemotherapy following vaccination. A relative low count of lymphocytes before and after vaccination was present in 11/19 patients indicating that these patients were immunocompromised. This study shows that HPV16 E7 peptide vaccination is feasible, even in a group of patients with terminal disease. This paves the way for vaccinating patients with less advanced disease, whose immune system is less compromised by progressive disease.

Adult↗

PubMed1999

Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis.

The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established. However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have investigated the role of several (onco)genes in cervical carcinoma. In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor (EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases, tumor diameter, vessel invasion, and disease-free and overall survival. Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this expression was correlated to p53 expression (P<0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free (P = 0.002) and overall survival (P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph node status. Gene amplification was found for EGFR (four cases), c-erbB-2/ neu (two cases), and c-myc (six cases). In two tumors, rearrangement of c-myc was found, probably due to the integration of HPV. In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.

Adult↗

PubMed1998

Allelic loss and prognosis in carcinoma of the uterine cervix.

Cervical carcinomas develop as a result of multiple genetic alterations. As the genetic alterations are the cause of malignant transformation, it is likely that specific genetic alterations lead to specific clinical behaviour. The aim of this study was (i) to localise chromosome arms that harbour likely tumour-suppressor genes, by analysing loss of heterozygosity (LOH) and (ii) to study the association of LOH with clinicopathological parameters. To define the regions of interest, we studied the presence of loss of heterozygosity at all chromosomes in 67 cervical carcinomas (stages IB and IIA) with 81 polymorphic markers. In addition, all frequent allelic imbalances were correlated with HPV status and clinicopathologic parameters including survival, FIGO-stage, lymph-node metastasis, tumour size, number of mitoses, vaso-invasion and histologic type. LOH at a frequency over 25% was observed at sites on 9 chromosome arms: 3p21, 4p16.1-15, 6p, 6q22.3-23.1, 11q22-24, 15q11-21.1, 17p13.3, 18q22-qter and Xq. LOH of chromosome 6q14-16.2, 6p22 and 17p13 correlated marginally with HPV-16 positivity. LOH on chromosome 3p21 was weakly correlated with high mitotic activity, while LOH on chromosomes 11q23.3, 15q21.1 and 17p13 correlated with low mitotic activity. LOH at chromosome 17p13 associated marginally with FIGO stage I, while LOH at chromosome 15q associated weakly with FIGO stage II. When chromosome 18q showed LOH in the tumour, the patients had decreased survival (p = 0.024). We conclude that, in carcinoma of the uterine cervix, a novel tumour-suppressor gene may be present on chromosome 15q21 and that patients with LOH on chromosome 18q have relatively poor survival (p = 0.025).

Adult↗

PubMed1997

p53 protein overexpression is common and independent of human papillomavirus infection in squamous cell carcinoma of the vulva.

BACKGROUND: Human papillomavirus (HPV) infection and p53 abnormalities might both play a role in the carcinogenesis of subtypes of squamous cell carcinoma of the vulva. In this study, the authors investigated the prevalence of and the relationship between p53 overexpression and HPV infection in patients with vulvar carcinoma. METHODS: Immunohistochemical methods for the detection of p53 protein and consensus primer polymerase chain reaction (PCR) were used, followed by direct sequencing of the PCR product for the evaluation of HPV subtype infection. Sixty-six patients with squamous cell carcinoma of the vulva were available for this study. RESULTS: DO7, an anti-p53 monoclonal antibody, showed p53 overexpression in 35 carcinomas (53%). Consensus primer PCR showed HPV infection in 12 carcinomas (18%). No significant association was observed between p53 overexpression or HPV infection and tumor subtype. Approximately 57% of the HPV negative carcinomas and 33% of the HPV positive carcinomas had p53 overexpression. With regard to the patients with DO7 positivity in > or =50% of the nuclei only, significantly more HPV negative carcinomas were DO7 positive compared with HPV positive carcinomas (41% vs. 0%, respectively; P = 0.018). No relation was found between either HPV infection or p53 overexpression and disease free survival. CONCLUSIONS: p53 overexpression is common in both HPV positive and HPV negative carcinomas of the vulva. These findings indicate that these two both play a role in the pathogenesis of vulvar carcinoma, but do not influence disease free survival.

Adult↗

PubMed1997

Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin.

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) infection in various vulvar lesions. METHODS: HPV infection using consensus primer-PCR was studied in 66 patients with vulvar carcinoma and in the synchronous epithelial lesions. RESULTS: HPV infection was present in 13/66 carcinoma, in 1/33 VIN I, in 3/11 VIN II, in 8/16 VIN III, in 2/30 lichen sclerosus, in 1/37 squamous cell hyperplasia, and in 2/55 normal skin specimens. Normal skin from healthy controls showed HPV-negative specimens only. Patients with HPV-positive carcinomas were younger, presented in lower stages, and had high-grade VIN more often than those with HPV-negative carcinomas. CONCLUSIONS: In sum we found that all types of epithelial changes synchronous with carcinoma of the vulva showed HPV infection, indicating that they all might have malignant potential.

Adult↗

PubMed1997

The relevance of various vulvar epithelial changes in the early detection of squamous cell carcinoma of the vulva.

The objective of this study is to evaluate the possible relevance of vulvar epithelial changes as a risk factor for squamous cell carcinoma of the vulva. The data of 66 women surgically treated for squamous cell carcinoma of the vulva have been analyzed. More than 6500 slides from the resection specimens were revised with special emphasis on concurrent epithelial changes. Synchronous epithelial changes were seen in 63 patients. Thirty-nine patients had synchronous vulvar intra-epithelial neoplasia grade 1 (VIN I), 10 VIN II and 13 VIN III. Thirty-one patients had synchronous lichen sclerosus and 49 squamous cell hyperplasia. The difference between the percentage of patients with epithelial changes diagnosed preceding their carcinoma (30%) and the percentage of patients that had synchronous epithelial changes after reviewing the specimen (95%) was striking. It was concluded that more careful diagnosis, treatment and follow-up of these conditions might lead to an earlier recognition of squamous cell carcinoma of the vulva and therefore to a better prognosis.

Journal Article↗

PubMed1997

p53 protein overexpression, a frequent observation in squamous cell carcinoma of the vulva and in various synchronous vulvar epithelia, has no value as a prognostic parameter.

In this study we have investigated the prevalence of p53 overexpression in various vulvar lesions and its significance as a prognostic parameter in patients with vulvar carcinoma. Overexpression of p53 was studied in 66 patients with squamous cell carcinoma of the vulva and in the following synchronous epithelial lesions: intraepithelial neoplasia grade I (VIN I) (n = 33), VIN II (n = 11), VIN III (n = 16), lichen sclerosus (n = 30), squamous cell hyperplasia (n = 37), normal vulvar skin of patients with vulvar carcinoma (n = 55), and in 18 samples of normal skin from healthy controls. Survival curves of the p53-positive and p53-negative patients were compared using the log-rank test. The use of DO7, and anti-p53 monoclonal antibody, showed p53 overexpression in 35 (53%) specimens of carcinoma, in eight (27%) of lichen sclerosus, in five (14%) of squamous cell hyperplasia, in six (18%) of VIN I, in two (18%) of VIN II, in two (13%) of VIN III, and in seven (13%) specimens of normal vulvar skin. Staining of normal skin from healthy controls showed no p53 positive specimens. No relationship between expression of p53 and disease-free survival in patients with vulvar carcinoma was present. In malignant, synchronous premalignant and non-neoplastic epithelial disorders of the vulva, p53 overexpression is a frequent observation, indicating that the latter two groups have characteristics of premalignant lesions. In addition, p53 overexpression was not a useful prognostic parameter for patients with vulvar carcinoma.

Carcinoma, Squamous Cell↗

PubMed1996

[Sexual problems and experiences with sexual and physical violence in gynecological patients].

OBJECTIVE: To determine the frequency of sexual difficulties and of sexual and physical abuse. DESIGN: Descriptive survey study. SETTING: Outpatient gynaecology clinic of the University Hospital of Leiden, the Netherlands. PATIENTS AND METHOD: During 3 months, December 1994-February 1995, all consecutive new female patients were questioned by the gynaecologist by means of a short standardised questionnaire. Oncology patients and non-Dutch-speaking patients were excluded. Data were analysed with descriptive statistical procedures; relationships among variables were tested with the chi 2 test with Yates' correction or Fisher's exact test. RESULTS: Of 325 patients 34.2% reported sexual difficulties, 15.4% reported sexual abuse and 7.4% physical molestation. Age of the patient and presence or absence of the partner during the consultation were not associated with differences in the patients' reports. 18.8% of the patients with these complaints answered affirmatively when asked if they needed specialised help. CONCLUSION: Sexual difficulties and sexual and physical abuse were common among gynaecology patients. Less than one-fifth of them required specialised help.

Adolescent↗

PubMed1996

The cytological screening history of 469 patients with squamous cell carcinoma of the cervix uteri; does interval carcinoma exist?

BACKGROUND: To determine whether interval carcinomas occurred and to determine the level of screening-participation by women who developed a cervical carcinoma. METHODS: A retrospective study of the cytological history of 469 patients diagnosed between January 1980 and December 1989 with cervical squamous cell carcinoma in 12 hospitals in the western part of The Netherlands. Clinical data, and cervical smear histories in 3.5 years preceding the diagnoses were obtained. Cervical smears diagnosed as Pap I, II or IIIA were traced for review. RESULTS: 306 patients' data were completed. Two hundred and twenty-three patients (72.9%) had never been screened and 83 patients (27.1%) had had at least one smear, of which 39 were normal. The percentage of women over 54 was higher in patients who had never been screened (58%) than in those screened (46%). Women over 54 were in higher Figo stage. Interval carcinoma was proven in six of 306 (2%) patients. Of the normal smears 53% were false negative. CONCLUSION: The high number of non-participants still forms the main reason for the failure of cervical cancer screening. Secondly, the assumed existence of frequent interval carcinoma could not be demonstrated. There are grounds for changing the age limits of the current Dutch screening program without changing the screening interval.

Adult↗

PubMed1995

Clinical value of pretreatment serum Cyfra 21-1, tissue polypeptide antigen, and squamous cell carcinoma antigen levels in patients with cervical cancer.

BACKGROUND: The clinical value of pretreatment serum concentrations of cytokeratin 19 fragments, measured by Cyfra 21-1, was compared with tissue polypeptide antigen (TPA) and squamous cell carcinoma antigen (SCC-Ag) in 78 patients with squamous cell cervical cancer. METHODS: Serum levels were compared with tumor stage, size, lymph node status, parametrial involvement, and prognostic data. The clinical performance of the different tests was evaluated by their receiver operating characteristic (ROC) curves. RESULTS: Serum levels of all markers were related significantly to tumor stage and size. Elevated serum levels of these markers were not found to be predictive for the presence of lymph node metastases. In contrast, a positive relation was found between quantitative serum Cyfra 21-1, TPA, and SCC-Ag levels and the presence of either lymph node metastases or parametrial involvement (i.e., extracervical disease). An elevated, i.e. positive, serum Cyfra 21-1 level was related significantly to the presence of extracervical disease (P = 0.020). The clinical performance of each serum marker in predicting lymph node metastases or parametrial involvement appeared to be similar as expressed by their ROC curves. In the univariate analysis, Cyfra 21-1, TPA, and SCC-Ag showed prognostic value with respect to disease free interval and survival. Elevated serum levels were associated with a poor prognosis. However, after adjusting for tumor stage and size, none of these markers remained statistically significant. CONCLUSIONS: Cyfra 21-1 may be of additional value in assessing stage of disease, tumor size, and the presence of extracervical disease in patients with cervical cancer. Determining its value during follow-up warrants further study.

Adult↗

PubMed1994

Prognostic significance of serum antibodies to human papillomavirus-16 E4 and E7 peptides in cervical cancer.

BACKGROUND: The objective of this study was to investigate the prognostic significance of serum antibodies to human papillomavirus (HPV)-16 peptides in patients with squamous cell cervical cancer. METHODS: Pretreatment sera from 78 patients and 198 control women were tested by an enzyme-linked immunosorbent assay technique for reactivity with HPV-16 E4 (E401p) and E7 (E701p) synthetic peptides. The presence and serum level of these antibodies were correlated with tumor stage, histologic features, and prognostic parameters. RESULTS: The median follow-up was 65 months (range, 6-97 months). Antibodies to E401p peptide were found in 5 of the 198 (3%) control subjects, 4 of the 43 (9%) patients with low tumor stage (International Federation of Gynecology and Obstetrics [FIGO] Ia, Ib, IIa), and 7 of the 35 (20%) patients with advanced tumor stage (FIGO IIb, III, IVa). Antibodies to E701p were found in 25 (13%), 11 (26%), and 11 (31%) women, respectively. The differences between patients and control subjects were significant (P < 0.002). Seropositivity against these peptides showed no correlation with tumor stage. Antibody levels to both peptides were significantly higher in patients compared with control subjects (P < 0.05). Furthermore, antibody levels to E401p were higher in patients with advanced tumor stage versus patients with low tumor stage (P = 0.0097). Such a relation was not found for anti-E701p antibodies. In the univariate analysis, a high level of anti-E701p antibodies was associated with a shorter disease free interval (P = 0.012) and poor survival (P = 0.049). However, this variable possessed no prognostic value after adjusting for FIGO stage and tumor size. CONCLUSIONS: The authors' findings indicate that the prognostic significance of serum antibodies to the HPV-16 E4 and E7 peptides used in this study of patients with cervical cancer is limited.

Adult↗

PubMed1994

Prognostic significance of serum fragments of cytokeratin 19 measured by Cyfra 21-1 in cervical cancer.

Pretreatment sera of 78 patients with squamous cell cervical cancer were tested for the presence of cytokeratin 19 (CK 19) fragments to determine the relationship among this parameter, tumor stage, various histopathologic characteristics, and prognosis. For the quantitative determination of CK 19 fragments in serum, the enzyme assay Cyfra 21-1 was used. This assay, based on the simultaneous sandwich principle, utilizes two different monoclonal antibodies. The test was considered positive when levels of Cyfra 21-1 were > or = 1.2 micrograms/liter. Cyfra 21-1 was positive in the majority of patients and in all patients with advanced disease (FIGO III or IVa). A highly significant relationship was found between pretreatment Cyfra 21-1 level and FIGO stage (P < 0.0001). Mean Cyfra 21-1 concentration was elevated in the case of macroinvasive disease (FIGO Ib, IIa, IIb, III, IVa). A distinct relationship was found between tumor size (P < 0.001; r = 0.73) and Cyfra 21-1 level. In the univariate Cox analysis Cyfra 21-1 level was significantly related to both disease-free interval (P < 0.0001) and survival (P < 0.0001) of patients. Patients with an increased Cyfra 21-1 level had a significantly worse prognosis. However, in the stepwise Cox regression analysis, these variables had no additional value over known prognostic factors such as FIGO stage and tumor size. It is concluded that Cyfra 21-1 may be of significance as an additional marker in the management of patients with cervical cancer, but further investigation is needed.

Adult↗