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Biomedical subjects

C Kainz

Publications and source records attributed to C Kainz.

At least 55 records · Page 3Linked to original sources

The influence of vascular space involvement on the prognosis of patients with stage IB cervical carcinoma: correlation of results from hematoxylin and eosin staining with results from immunostaining for factor VIII-related antigen.

BACKGROUND: There is controversy over the question of whether the involvement of vascular spaces influences the prognosis of patients with carcinoma of the uterine cervix. The aim of the current study was to compare patterns of vascular space involvement determined by hematoxylin and eosin (H & E) staining with those patterns determined by immunostaining for factor VIII-related antigen (F8-RA) with regard to their prognostic impact on the disease free survival (DFS) and overall survival (OS) of patients with clinical Stage IB cervical carcinoma. Staining for F8-RA is known to highlight blood vessels predominantly, whereas the presence of tumor cell emboli in vascular spaces of H & E-stained sections mainly indicates lymphatic vessel invasion. METHODS: The authors analyzed data on 163 patients for whom vascular space involvement (VSI) was determined by H & E (VSI/H & E) and F8-RA (VSI/F8) staining from the same block in two separate runs. RESULTS: The median follow-up period was 85 months (range, 5-170 months). The 25% quantile for OS was 109 months (median not reached; range, 5-170 months). The overall rates of VSI/H & E and VSI/F8 were 29.4% and 24.5%, respectively. The findings obtained by H & E and F8-RA staining were concurrent in 60.7% of cases. Lymph node involvement and VSI/F8 remained independent prognostic factors for DFS and OS. Due to a highly significant correlation of pelvic lymph node status with both VSI/H & E and tumor size, the last two parameters failed to retain a significant value. For lymph node negative patients, the estimated OS probability was 92% for those without VSI/F8 and 62% for those with VSI/F8. CONCLUSIONS: VSI/F8 may provide additional information on the outcome of clinical Stage IB cervical carcinoma. Lymph node negative patients with VSI/F8 positive tumors may benefit from more intense postsurgical treatment. Further trials involving larger series of patients are necessary to confirm these findings.

Adenocarcinoma↗

Absence of p53 protein overexpression in precancerous lesions of the vulva.

BACKGROUND: Recently the authors reported the prognostic value of p53 protein overexpression in invasive squamous cell carcinoma of the vulva. The aim of this study was to evaluate the status of p53 overexpression and human papillomavirus (HPV) infection in patients with precancerous lesions of the vulva. METHODS: Biopsy specimens of 28 women (mean age, 44.2 years; range, 19-71 years) with warty and/or basaloid type vulvar intraepithelial neoplasia (VIN) of Grade 1 to 3 were examined retrospectively for p53 protein overexpression by immunohistochemistry. The presence of the HPV genome was assessed using a nested polymerase chain reaction (PCR) method with consensus primers directed against the L1 coding region. RESULTS: Neither the preoperative punch biopsy specimen nor the subsequent surgical specimen contained immunohistochemically detectable levels of p53 in this study of a group of younger women with preinvasive vulvar lesions. These results are in contrast to those obtained previously in older women with keratinizing squamous cell carcinoma demonstrating p53 protein overexpression in approximately 50% of patients. HPV DNA was detected in the vast majority of VIN cases (92.8%) using a highly sensitive nested PCR method. The current data indicate that p53 protein is not overexpressed in basaloid/warty VIN when evaluated by immunohistochemistry. In addition, this study confirms previous reports demonstrating the presence of HPV DNA in the majority of these lesions. CONCLUSIONS: These data suggest that p53 protein overexpression is not an early event in the pathogenesis of basaloid/warty type vulvar dysplasia and that HPV infection may contribute to the development of VIN.

Adolescent↗

Embryonal rhabdomyosarcoma of the uterine cervix: case report and review of the literature.

Embryonal rhabdomyosarcoma (RMS) of the female genital tract usually occurs during childhood in the vagina. In rare cases, RMS can originate in the uterine cervix, with a peak incidence in the second decade. A combined modality approach to treating RMS using multidrug chemotherapy, radiotherapy, and surgery has markedly improved survival. Early stage embryonal RMS of the cervix has been found to have an excellent prognosis. The present case and literature review indicate that extensive surgery does not improve survival in patients with stage I disease.

Adult↗

Vascular endothelial growth factor serum concentrations in ovarian cancer.

OBJECTIVE: To determine whether serum vascular endothelial growth factor is an independent prognostic factor in ovarian cancer patients. METHODS: We measured vascular endothelial growth factor in pretreatment serum samples of 60 women with International Federation of Gynecology and Obstetrics stages I to IV epithelial ovarian cancer, using an enzyme-linked immunosorbent assay. The results were correlated to clinical data. RESULTS: The median vascular endothelial growth factor serum level in ovarian cancer patients was 466.1 pg/mL (range 69.7-2835 pg/mL). The 75% quartile was defined as a cut-off level. Elevated vascular endothelial growth factor serum levels before therapy correlated significantly with a poorer disease-free (log-rank-test, P = .003) and overall survival (log-rank-test, P = .007). Multivariate analysis revealed serum vascular endothelial growth factor to be an independent prognostic factor of overall and disease-free survival. When median pretreatment levels of vascular endothelial growth factor were grouped by tumor stage, histologic grade of tumor cells, histologic type of the tumor, lymph node involvement, age of patient, and residual tumor mass, we found a statistically significant correlation between serum levels of vascular endothelial growth factor and histologic grade (Mann-Whitney U test, P = .03). CONCLUSION: Vascular endothelial growth factor appears to be an additional factor for predicting the outcome of patients with epithelial ovarian cancer. Owing to its independence from established prognostic factors, vascular endothelial growth factor could be used for prognostic information in clinically relevant subsets such as early-stage or lymph node-negative ovarian cancers.

Adult↗

Influence of acupuncture on maternal serum levels of interleukin-8, prostaglandin F2alpha, and beta-endorphin: a matched pair study.

OBJECTIVE: To measure the serum levels of interleukin (IL)-8, prostaglandin (PG) F2alpha, and beta-endorphin in parturients with acupuncture treatment and in controls to clarify the effect of acupuncture and duration of labor on the serum levels of substances active in cervical ripening and dilatation. METHODS: A matched pair study was performed involving 80 women with and without prenatal acupuncture treatment, matched for age and parity. Serum levels of IL-8, PGF2alpha, and beta-endorphin were measured in serum samples taken after delivery by use of enzyme-linked immunosorbent assay, enzyme immunoassay, and immunoradiometric assay, respectively. RESULTS: The mean difference in total duration of labor between matched pairs with and without acupuncture was -136.5 minutes (95% confidence interval [CI] 191.1 minutes, -81.9 minutes; paired t test, P < .001). The mean difference of the duration of the first and second stages of labor between matched pairs with and without acupuncture was -138.8 minutes (95% CI 188.6, -89.0 minutes; paired t test, P < .001) and 2.3 minutes (95% CI 15.5, 20.1 minutes; paired t test, P = .8), respectively. The geometric means of ratios of IL-8, PGF2alpha, and beta-endorphin between matched pairs in women with and without acupuncture showed no statistically significant differences. Serum levels of IL-8, PGF2alpha, and beta-endorphin were not significantly correlated with the duration of the first and second stages of labor. CONCLUSION: Prenatal acupuncture treatment significantly reduces the duration of labor and may be a valuable tool in prenatal preparation. Serum levels of IL-8, PGF2alpha, and beta-endorphin are not significantly influenced by acupuncture and are therefore not likely to mediate acupuncture-related effects during labor.

Acupuncture Analgesia↗

Serum interleukin 1 in ovarian cancer patients.

Interleukin-1 (IL-1) is a multifunctional cytokine playing a central role in the immune response and displaying direct cytotoxic activity in vitro. Serum IL-1 alpha and beta levels were measured by enzyme linked immunosorbent assay (ELISA) in 75 ovarian cancer patients, 30 patients with benign ovarian cysts and 50 healthy controls. Both serum IL-1 alpha and IL-1 beta levels were more often elevated in ovarian cancer patients compared with healthy controls (chi-square test, P < 0.001 and P < 0.001, respectively). Mean serum IL-1 alpha and beta levels decreased significantly after surgical intervention (paired t-test, P = 0.0001 and P = 0.0002, respectively). No correlation with histopathological parameters and overall and disease-free survival was found. These preliminary results indicate that serum levels of IL-1 alpha and beta represent a host defence reaction rather than an autonomous tumour cell production.

Adult↗

The prognostic value of CD44 isoform expression in endometrial cancer.

Isoforms of the transmembrane glycoprotein CD44 have been implicated in tumour cell adhesion, tumour differentiation and metastatic spread in various human malignancies. We investigated the expression of CD44 isoforms containing variant exons v3, v5, v6 and v7-8 in 156 human endometrium cancer specimens by means of immunohistochemistry. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were detected in 26% (41 out of 156), 31% (48 out of 156), 22% (35 out of 156) and 15% (23 out of 156) of the tumour samples respectively. The expression of CD44 isoforms CD44v3, CD44v5 and CD44v7-8 showed no prognostic impact. In the univariate analysis, the expression of CD44v6 showed an association with shortened overall survival (log-rank test, P = 0.06). Multivariate analysis correcting for the confounding variable histological grading revealed CD44v6 not to be a prognostic factor in endometrial cancer (log-rank test, P = 0.06). Comparing the expression of CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 in 45 specimens of normal endometrial tissue, we found an up-regulation of all investigated CD44 isoforms in the secretory phase compared with the proliferative phase of the menstrual cycle. Our data indicate that the expression of CD44 isoforms, while obviously playing a role in the functional changes of normal endometrium, is not an adverse predictive factor in endometrial cancer.

Aged↗

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer.

As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml(-1), VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass.

Adult↗

Prognostic value of cathepsin D expression and association with histomorphological subtypes in breast cancer.

This study investigated the prognostic value of immunohistochemically detected cathepsin D expression in 103 invasive ductal carcinomas of the breast at stages pT1 and 2. We also assessed the association between cathepsin D expression and histomorphological tumour subtypes (invasive ductal carcinoma with extensive intraductal component, multifocal tumour). Cathepsin D expression was examined at two cut-off levels (positive and highly positive) and separately identified within the epithelial and stromal component of all tumours. Positive and highly positive epithelial expression was detected in 32 (31.1%) and 20 (19.4%) patients respectively. Stromal expression was found in 35 (34%) and 19 (18.4%) cases respectively. Epithelial cathepsin D expression was associated with stage and nuclear grade, but not with lymph node or oestrogen receptor status. Positive and highly positive epithelial cathepsin D expression showed significant prognostic value for overall survival (P = 0.003 and 0.01) and recurrence-free interval (P = 0.04 and 0.02). Cathepsin D expression in stromal cells was not associated with either several established prognostic factors or survival. Multivariate analysis revealed that cathepsin D expression failed to be an independent predictor of patients' outcome. Cathepsin D expression shows no significant association with histomorphological subtypes of breast cancer. Our study supports the prognostic impact of immunohistochemically detected cathepsin D expression in the epithelial component of breast cancer.

Adult↗

CD44v3 and v6 variant isoform expression correlates with poor prognosis in early-stage vulvar cancer.

Expression of alternatively spliced CD44 isoforms has been reported to correlate with poor prognosis in human squamous cell cancers, i.e. squamous cell cancer of the lung and cervix. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early-stage squamous cell cancer of the vulva. Seventy cases of squamous cell carcinoma of the vulva International Federation of Gynaecology and Obstetrics (FIGO) stage I were examined immunohistochemically for expression of CD44 isoforms. We used four different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exons v3, v5, v6 and v7-8 of human variant CD44. The correlation of CD44 expression with histological grade and disease-free and overall survival was investigated. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were detected in 28% (20/70), 47% (33/70), 33% (23/70) and 17% (12/70) of the tumour samples respectively. Patients suffering from tumours expressing CD44v6 had a poorer relapse-free (log-rank test, P = 0.02) and overall survival (log-rank test, P = 0.03). Likewise, patients suffering from tumours expressing CD44v3 had a poorer relapse-free (log-rank test, P = 0.04) and overall survival (log-rank test, P = 0.01). Expression of CD44v5 and CD44v7-8 did not compromise the patients' outcome. Histological grade did not correlate with CD44 isoform expression. Immunohistochemically detected expression of CD44 isoforms containing variant exon v6 or v3 is correlated with a poor relapse-free and overall survival in FIGO stage I vulvar cancer patients.

Adult↗

CYFRA 21-1 serum levels in women with adnexal masses and inflammatory diseases.

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin marker CYFRA 21-1 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic marker in women suffering from ovarian cancer. In order to determine the specificity of the CYFRA 21-1 test, we have investigated CYFRA 21-1 serum levels in several benign conditions. This retrospective study comprises 37 patients suffering from ovarian cancer FIGO stages Ia-III. Sera from patients with benign ovarian cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases respectively. With a sensitivity of 41% and a specificity of 95%, CYFRA 21-1 was not suitable as a screening marker for ovarian cancer. Although CYFRA 21-1 was able to discriminate between ovarian cancer and benign adnexal tumours (univariate regression model, P = 0.0001), CYFRA 21-1 did not reveal additional information to CA 125 in a multivariate regression analysis (P = 0.06). CYFRA 21-1 serum levels were elevated in benign conditions such as liver cirrhosis, but not in endometriosis and inflammatory diseases. In ovarian cancer patients, elevated CYFRA 21-1 serum levels before therapy were associated with a poor overall and disease-free survival (log-rank test, P = 0.02 and log-rank test, P = 0.005 respectively). CYFRA 21-1, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.

Adnexal Diseases↗

[Massive edema of the ovary].

Massive edema of the ovary is a rare condition found in young women as a result of partial or intermittent torsion of the ovary. Differentiation of this entity from tumors of the ovary is important to prevent overtreatment. Organ-preserving surgical treatment is indicated as the correct approach to management. We present a case of massive edema of the ovary associated with post partum involution of the female genital tract and discuss the clinical features in the light of the known literature.

Adult↗

Vascular endothelial growth factor (VEGF) in human breast cancer: correlation with disease-free survival.

Studies have shown that microvessel density influences breast-cancer prognosis. Since tumor angiogenesis is considered to be substantially affected by the excretion of vascular endothelial growth factor (VEGF) from tumor cells, we examined whether VEGF concentration is different in malignant and in non-malignant breast tissue. It was also of interest to discover whether intratumoral VEGF concentration influences disease-free survival (DFS) of breast-cancer patients. Analysis is based on 120 tissue specimens taken from breast fibromas (n = 23), normal epithelial breast tissue adjacent to fibromas (n = 8) and invasive breast cancer (n = 89). VEGF concentration was quantified by using an immunoassay. Microvessel density was determined by immunostaining for factor-VIII-related antigen. Median VEGF concentration is given in pg/mg protein (25%-quantile-75%-quantile) and it was 0 (0-1.8) in normal breast tissue, 9.8 (0.52-43.0) in fibromas and 130.4 (50.8-362.2) in invasive carcinomas. A univariate Cox model revealed that node status, tumor size, estrogen-receptor concentration, histological grading and microvessel density were prognostic factors for disease-free survival in breast cancer. We found a significant correlation between VEGF concentration and microvessel count, but VEGF concentration did not significantly influence disease-free survival. Although VEGF protein was found at a significantly higher concentration in malignant than in non-malignant tissue, determination of intratumoral VEGF protein by an enzyme immunoassay was not prognostically relevant in our patient population.

Analysis of Variance↗

CD44 is an independent prognostic factor in early-stage cervical cancer.

The expression of specific cell-adhesion molecule CD44 isoforms (splice variants) is associated with metastatic spread and poor prognosis in human malignancies. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early-stage cervical cancer. We used 4 different variant exon sequence-specific murine monoclonal antibodies to the CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 to study the prognostic value of CD44 splice variants in 200 cases of International Federation of Gynecology and Obstetrics (FIGO) stage-IB cervical cancer by immunohistochemistry. In the univariate analysis, the expression of CD44v3 (log-rank test, p = 0.03) and CD44v6 (log-rank test, p = 0.03) was correlated with poor overall survival. In the subgroup of patients without metastatic disease in the pelvic lymph nodes, expression of CD44v6 was correlated with poor disease-free and overall survival (log-rank test, p = 0.04 and p = 0.01, respectively). Multivariate analysis, correcting for the confounding variables pelvic lymph-node involvement, depth of invasion and histologic grading, revealed CD44v6 to be an independent prognostic factor for overall survival of patients with early-stage cervical cancer. The results of this study indicate that CD44v6 is an additional prognostic marker in surgically treated cervical cancer. The assessment of CD44 isoform expression could be of clinical value in deciding upon adjuvant therapy, resulting in a more individualized management of therapy.

Adult↗

Detection of p53 point mutations in primary human vulvar cancer by PCR and temperature gradient gel electrophoresis.

Clinical and experimental evidence is consistent with a key role of point mutations of the p53 tumor suppressor gene in the etiology of squamous cell carcinoma. To determine the relation of tumor behavior and patient survival in vulvar cancer in regard to p53 status, we retrospectively analyzed 38 paraffin-embedded specimens of primary vulvar cancer for genetic alterations of exons 5-8 of the p53 gene. For detection of p53 point mutations we used in vitro amplification by polymerase chain reaction (PCR) and temperature gradient gel electrophoresis (TGGE) and, as a detection method, direct sequencing for mutation verification. p53 point mutations were detected in 12/38 tumor specimens. Patients bearing p53 point mutations showed a significantly shorter relapse-free (log-rank test, P = 0.002) and overall survival time (log-rank test, P = 0.0006). We conclude that PCR-TGGE is an appropriate method for detection of p53 point mutations in paraffin-embedded material. We show that loss of wild-type p53 is an adverse prognostic factor in patients suffering from vulvar cancer.

Adult↗

Epithelial and stromal estrogen and progesterone receptor expression in endometrial cancer: true color computer-assisted image analysis versus subjective scoring.

Immunohistochemical methods provide the opportunity to evaluate the staining reaction in different histologic compartments of malignant tumors. Eighty-four formalin-fixed, paraffin-embedded and immunohistochemically stained endometrial cancer specimens were assessed for estrogen receptor (ER) and progesterone receptor (PR) expression by conventional light microscopy, a light microscopy scoring system, and by true color computer-assisted image analysis. Measurements of mean optical density (MOD) in the epithelium as well as in the stroma of the tumor were performed. A negative correlation was established between the MOD of ER and PR staining in the nuclei of the epithelium and the MOD of PR staining in the stroma of the tumor vs histological stage (Spearman correlation coefficient -0.32/P < 0.004, -0.23/P < 0.03, -0.26/P < 0.02, respectively) and depth of myometrial invasion (Spearman correlation coefficient -0.34/P < 0.002, -0.24/P < 0.02, -0.25/P < 0.02, respectively). The staining pattern in endometrial cancer was heterogeneous and %PA (percentage of positive stained area) and MOD were therefore linked by multiplication in order to correct for this potentially confounding phenomenon. A negative correlation with histological stage (Spearman correlation coefficient -0.29/P < 0.007) and depth of myometrial invasion (Spearman correlation coefficient -0.34/P < 0.001) was found for PR staining in the stroma of the tumor. MOD and subjective ranking of staining intensity showed a high correlation as well as %PA and subjective estimation of stained surface. ER and PR content in the epithelium and also PR content in the stroma of endometrial cancer appear to be of value in the assessment of steroid hormone receptor status. This may be indicative of stromal-epithelial interaction.

Adenocarcinoma↗

Angiogenesis in vulvar intraepithelial neoplasia.

Vulvar intraepithelial neoplasia (VIN) has been reported to be a precursor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) and vascular endothelial growth factor (VEGF), a highly angiogenic peptide, are important parameters of tumor angiogenesis. Forty-three histologic slides with 38 VIN I-III lesions were immunohistochemically stained for factor VIII-related antigen (F8-RA) and 44 slides with 37 VIN I-III for VEGF, since F8-RA reliably highlights tumor microvessels. Determination of MVD and VEGF expression was done by counting microvessels and VEGF-positive cells at a magnification of 200x and 400x. The highest concentration of F8-RA-stained MVD and VEGF expression was found at a small subepithelial area at the border of the VIN lesion to the stroma underneath but concentrations were low in all specimens of normal epithelium. High VEGF expression was significantly correlated to high MVD. For both MVD and VEGF expression the differences between VIN I and VIN III and between VIN II and VIN III were statistically significant (P < 0.0001). VIN III lesions are the clinical relevant precursors of invasive cancer of the vulva, as outlined by intense expression of VEGF protein and a highly dense network of microvessels underlying the dysplastic epithelium.

Adult↗

Serum evaluation of interleukin 6 in ovarian cancer patients.

BACKGROUND: Cytokines are intercellular hormones, believed to play a functional role in the natural history of various malignant diseases. In vitro and in vivo studies have indicated that interleukin 6 (IL-6) may provide autocrine and paracrine growth stimulation in ovarian cancer cells. METHODS: In the present study we measured IL-6 in the serum of 73 patients with FIGO stage I to IV ovarian cancer. Enzyme-linked immunosorbent assay (ELISA) was used to determine IL-6 serum levels. Results were correlated to clinical data. Serum levels of IL-6 were additionally evaluated in a panel of 50 normal controls. RESULTS: Median serum levels of IL-6 in patients with ovarian cancer and normal controls were 55.6 (minimum 0, maximum 2869.0) pg/ml and 0.5 (minimum 0, maximum 2.14) pg/ml, respectively (Mann-Whitney U test, P = 0.0001). When serum levels of IL-6, taken prior to therapy, were grouped by FIGO stage, lymph node involvement, and grading of tumor cells, we found a statistically significant correlation with FIGO stage (Mann-Whitney U test, P = 0.04). Lymph node involvement and grading of tumor cells were not correlated with IL-6 levels. Elevated IL-6 serum levels prior to therapy were significantly correlated with poorer disease-free (log-rank test, P = 0.003) and overall survival (log-rank test, P = 0.01). CONCLUSION: Elevated IL-6 serum levels prior to therapy are correlated with a poor relapse-free and overall survival in ovarian cancer patients.

Adult↗