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H Hollema

Publications and source records attributed to H Hollema.

At least 91 records · Page 5Linked to original sources
PubMed1995

The importance of the groin node status for the survival of T1 and T2 vulval carcinoma patients.

The purpose of this study was to analyze (1) the prognostic factors for survival of T1 and T2 carcinoma patients and (2) the impact of the initial groin node status for the time to recurrence and site of recurrence. We performed a follow-up study on 190 women with a T1 or T2 squamous cell carcinoma of the vulva. Data were obtained on age and general medical condition, the clinical and histological characteristics of the primary tumor and the inguinofemoral lymph nodes, treatment, recurrences, and survival. The standard treatment was radical vulvectomy with bilateral inguinofemoral lymphadenectomy supplemented with postoperative radiotherapy to the primary site, groin, and pelvic side walls if groin metastases were present. Compared to patients without lymph node metastases in the groin, the relative risk of dying within a given time period was estimated to be 2.47 (limits of the 95% confidence interval: 1.24, 4.93) and 9.69 (3.90, 24.03) for patients with unilateral and bilateral node metastases, respectively. The number of metastatic lymph nodes or their intra- or extranodal growth was not associated with survival. The relative risk of dying within a given time period was 2.71 (1.36, 5.40) for patients with a T2 tumor compared to those with a T1 tumor and 2.37 (1.31, 4.31) for patients with vasoinvasive growth compared to those without capillary-lymphatic tumor infiltration. Tumor thickness, differentiation grade, and multifocal growth did not determine survival. In the multivariate Cox regression analysis, the presence of inguinofemoral lymph node metastases proved to be the most important prognostic factor for patients' survival. Of the 119 patients who underwent lymphadenectomy but in whom no groin node metastases were found, 6 (5%) patients manifested an early recurrence (i.e., residual cancer or a recurrence within 2 years after the diagnosis). In contrast, of the 51 patients with histologically documented groin node metastases, 15 (29.4%) manifested an early recurrence and these recurrences appeared equally distributed over the primary site and other sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Atypical mitotic figures and the mitotic index in cervical intraepithelial neoplasia.

We surveyed cervical intraepithelial neoplasia (CIN) to quantify the proliferation rate and the presence of normal and atypical mitotic figures. In the cervical tissue specimens of 127 women with CIN, the area with the highest cell proliferation was identified and, at that site, the proliferation rate was assessed by calculating the mitotic index (MI). Lesions with an MI < 2 were not considered further. In the area with the highest proliferation rate, 228 mitoses were classified into one of the following groups: normal mitotic figures (NMFs), lag-type mitoses (OLTMs) comprising three group metaphases (3GMs), two group metaphases (2GMs) and other lag-type mitoses (LTMs), multipolar mitoses (MPMs) comprising tripolar mitoses (3PMs) and quadripolar mitoses (4PMs), and other atypical mitotic figures (OAMFs). The median value of the MI increased significantly from 3 in CIN I through 4 in CIN II to 9 in CIN III (P < 0.001). The occurrence of the different LTMs was mutually correlated. The frequency of LTMs increased significantly with increasing CIN grade (P < 0.001), whereas the frequency of NMFs decreased significantly with increasing CIN grade (P < 0.001). The frequency of OAMFs was not related to CIN grade (P = 0.94). MPMs were present in low numbers in a minority of the lesions. Spearman's rank correlation coefficient (with 95% confidence limits) between the MI and the number of LTMs, OAMFs and NMFs was 0.66 (0.53; 0.75), -0.14 (-0.32; 0.05) and -0.51 (-0.63; -0.35), respectively. Increasing CIN grade is associated with increasing MI, increasing numbers of LTMs, and decreasing numbers of NMFs. MPMs are very rare events in CIN. The abundant presence of OAMFs seems to be independent of CIN grade and MI.

Adult↗
PubMed1995

Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas.

PURPOSE: To determine the prognostic value of immunostaining of P-glycoprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. PATIENTS AND METHODS: Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival. RESULTS: P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately. CONCLUSION: Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Quantitative and qualitative aspects of topoisomerase I and II alpha and beta in untreated and platinum/cyclophosphamide treated malignant ovarian tumors.

Quantitative and qualitative aspects of topoisomerase (Topo) I and II were studied in 17 malignant ovarian tumors [eight untreated and nine after platinum/cyclophosphamide (Pt/Cy) chemotherapy]. Median Topo II catalytic activity was lower (P < 0.05) in tumors after Pt/Cy chemotherapy in comparison to untreated tumors, while no differences were found for Topo I catalytic activity in tumors before and after chemotherapy, as was also found in a previous study (Van der Zee et al. Cancer Res., 51: 5915-5920, 1991). Teniposide (VM-26)-induced cleavable complex formation correlated (r = 0.60; P < 0.05) with Topo II activity, while Topo II decatenation activity was equally but incompletely inhibited by VM-26 in all tumors. No differences were found in Topo II cleavage site patterns in plasmid BR322 DNA for all tumors using an indirect end-labeling procedure. Cleavable complex formation of Topo I by camptothecin (Cpt) did not correlate with Topo I catalytic activity, while Topo I catalytic activity could equally and completely be inhibited by Cpt. By Western blotting, Topo II alpha protein expression was detected in four of eight untreated tumors and three of nine tumors after Pt/Cy chemotherapy, whereas in all tumors a M(r) 150,000 degradation product of Topo II beta was detected. Topo I protein was detected in all tumors at varying levels, but the protein levels did not correlate with Topo I catalytic activity or cleavable complex formation by Cpt. Our study shows that Topo I and II, isolated from human malignant tumors, can be stimulated by Cpt and VM-26, respectively, to induce DNA cleavage, which suggests that topoisomerases are real targets for chemotherapy in patients with ovarian cancer. From in vitro data from the literature it appears that the cleavable complex assay reflects both quantitative and qualitative changes as well as changes in the phosphorylation state of Topo I and II. In combination with the feasibility of the cleavable complex assay for Topo I and II in human malignant tumors, which was found in the present study, it appears that at present the determination of cleavable complex formation by tumors seems to be the most promising parameter of Topo I or II expression in human tumors to be related to response to Topo I- or II-targeted chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Primary cutaneous T-cell lymphoma: clinicopathological features and prognostic parameters of 35 cases other than mycosis fungoides and CD30-positive large cell lymphoma.

Within the group of primary cutaneous T-cell lymphomas (CTCLs), mycosis fungoides (MF), Sézary's syndrome (SS), and CD30-positive lymphomas have been delineated as clinicopathological entities. Primary CTCLs that do not belong to one of these entities represent a heterogeneous and ill-defined group of neoplasms. This paper describes the clinical and histological features of 35 of such cases. The object of this study was to define prognostic parameters for this group of primary CTCLs. Using a slightly modified version of the updated Kiel classification, a subdivision was made into CTCL, pleomorphic, small cell type (n = 3); pleomorphic, medium-sized cell type (n = 6); pleomorphic, large cell type (n = 18); and immunoblastic lymphomas (n = 8). Altogether, these lymphomas had a poor prognosis with estimated 2- and 4-year survival rates of 53 and 22 percent, respectively. Patients with pleomorphic, small and medium-sized cell lymphomas (n = 9) proved to have a significantly better survival than those with pleomorphic, large cell lymphomas (P = 0.032) and immunoblastic lymphomas (P = 0.008). Primary cutaneous immunoblastic lymphomas had the worst prognosis with an estimated 2-year survival rate of 14 percent. Other parameters including age (P = 0.345), sex (P = 0.662), extent of skin lesions at presentation (P = 0.0854), and mode of initial treatment (P = 0.609) had no significant effect on the survival time. The results of this study suggest that primary CTCLs other than classical MF, SS, and CD30-positive lymphomas have a poor prognosis in most cases, and that the current classification may be a useful means of predicting the clinical behaviour in these lymphomas.

Adult↗
PubMed1994

Molecular analysis of the topoisomerase II alpha gene and its expression in human ovarian cancer.

BACKGROUND: DNA topoisomerase II enzymes are key targets for the group of anti-tumour agents known as topoisomerase inhibitors. In general, cell lines which express high levels of topoisomerase II are sensitive to the cytotoxic effects of the topoisomerase poisons. The levels of topoisomerase II expression in tumour biopsies may therefore predict response to treatment with enzyme inhibitors. In the current study we have analysed ovarian tumours for expression of topoisomerase II alpha and genetic change at the topoisomerase II alpha locus on chromosome 17. MATERIALS AND METHODS: We have used methodology which allows the sequential extraction of protein and genomic DNA from the same biopsy sample to study the topoisomerase II alpha locus and the expression in ovarian cancer. Topoisomerase II alpha expression was quantified by Western blot analysis in 54 tumours. RESULTS: Topoisomerase II alpha expression was detected in 65% of ovarian tumours with a 16 fold range in level. In adenocarcinomas, the topoisomerase II alpha gene can become amplified due to its proximity to ERBB2 on chromosome 17q. Of 86 ovarian tumours studied only 1 had amplification of ERBB2 and none had amplification of topoisomerase II alpha a sequences. CONCLUSIONS: Topoisomerase II alpha expression was detected in ovarian carcinomas by Western blot analysis. A sixteen-fold range in expression was detected with significantly higher levels of topoisomerase II alpha expression in advanced stage IV and grade III tumours. Molecular analysis of the topoisomerase II alpha locus failed to reveal any gross genetic alterations which could account for the variation in levels of expression.

Adenocarcinoma↗
PubMed1993

Cigarette smoking and human papillomavirus in patients with reported cervical cytological abnormality.

OBJECTIVE: To assess the relation between two risk factors for cervical neoplasia: smoking and infection with oncogenic human papillomavirus. It has been suggested that smoking causes a local immunological defect, which could facilitate the infection and persistence of human papillomavirus. DESIGN: Cross sectional epidemiological study. Completion of a structured questionnaire by the patients, analysis of cervical scrapes for human papillomavirus, and morphological examination of biopsy specimens. SETTING: Outpatient gynaecological clinic. SUBJECTS: 181 women with a report of cervical cytological abnormality. MAIN OUTCOME MEASURES: Prevalence of infection with oncogenic human papillomavirus and smoking habits. RESULTS: Oncogenic human papillomavirus was found in the cervix of 26 (41%) of the 63 women who did not smoke, 22 (58%) of the 38 who smoked 1-10 cigarettes a day, 28 (61%) of the 46 who smoked 11-20 cigarettes a day, and 26 (76%) of the 34 who smoked > or = 21 cigarettes a day. The prevalence of the virus thus increased in accordance with the number of cigarettes smoked (p = 0.001). This relation remained after adjustment for age at first intercourse and lifetime number of sexual partners. Of the 63 non-smokers, 23 had previously smoked at least 10 cigarettes a day at some time. Of these 23 women, 14 (61%) had oncogenic human papillomavirus in their cervix. Of the 40 women who had never smoked at least 10 cigarettes a day, 12 (30%) had the virus. The prevalence of oncogenic human papillomavirus in non-smokers therefore depended on previous smoking habits (p = 0.03). CONCLUSION: The dose dependent effect of cigarette smoking on the occurrence of oncogenic human papillomavirus favours a causal relation between these risk factors for cervical neoplasia.

Adult↗
PubMed1993

Clonal chronic lymphocytic leukaemia-like B lymphocytes in the blood of patients with cutaneous T-cell disorders.

A population of B cells with characteristics of chronic lymphocytic leukaemia was found in the peripheral blood of four patients who presented with cutaneous infiltration of atypical CD4+ T cells with cerebriform nuclei. The B cells had a low density of immunoglobulin on their surface membrane, expressed CD5-positivity, and showed monoclonality based on the restriction to either kappa or lambda light chains. In one patient with tumourous pleiomorphic CD4+CD30- T-cell lymphoma of the skin, it was the first manifestation of a concomitant B-cell non-Hodgkin's lymphoma of low-grade malignancy. In three other patients with reactive atypical T-cell erythroderma, there was no evidence for the coexistence of a B-cell malignancy. The number of CD5+ B cells decreased in two erythroderma patients with clinical remission of the cutaneous lesions. It is speculated that the presence of a monoclonal B cell population in patients with T-cell disorders of the skin is due either to a reactive process possibly conferring some protective effect, or a response to an unknown stimulus produced by the T cells.

Aged↗
PubMed1992

Three-group metaphase as a morphologic criterion of progressive cervical intraepithelial neoplasia.

OBJECTIVE: The purpose of our study was to investigate the presence of three-group metaphase in progressive cervical intraepithelial neoplasia. STUDY DESIGN: This was a retrospective histologic study on the conization specimens of 41 women with microinvasive cervical carcinoma, 28 of whom were enrolled in the study. Three-group metaphase was scored in the invasive part of the lesion and in the adjacent cervical intraepithelial neoplasia. RESULTS: Three-group metaphase was found in 93% of cervical intraepithelial neoplasia adjacent to the invasive part of the lesion. However, three-group metaphase was found in 11% of the microinvasive cervical carcinoma cases with an infiltration depth of less than 2.5 mm and in 60% of the microinvasive cervical carcinoma cases with an infiltration depth of between 2.5 and 5.0 mm. CONCLUSION: The chance of finding three-group metaphase seems to be limited by the area of the lesion examined for three-group metaphase on the slide. Given the relation between three-group metaphase and aneuploid cervical intraepithelial neoplasia found in the literature and the occurrence of three-group metaphase in the cervical intraepithelial neoplasia adjacent to the microinvasive cervical carcinoma in this study, three-group metaphase can be considered a morphologic criterion for progressive cervical intraepithelial neoplasia and can be of value for practical use.

Cervix Uteri↗
PubMed1992

Glutathione S-transferase activity and isoenzyme composition in benign ovarian tumours, untreated malignant ovarian tumours, and malignant ovarian tumours after platinum/cyclophosphamide chemotherapy.

Glutathione S-transferase (GST) isoenzyme composition, isoenzyme quantities and enzymatic activity were investigated in benign (n = 4) ovarian tumours and malignant ovarian tumours, before (n = 20) and after (n = 16) chemotherapy. Enzymatic activity of GST in cytosols was measured by determining 1-chloro-2,4-dinitrobenzene conjugation with glutathione, cytosolic GST subunits were determined by wide pore reversed phase HPLC, using a S-hexylglutathione-agarose affinity column, and isoelectric focussing. Both GST activity and GST pi amount were not related to histopathologic type, differentiation grade, or tumour volume index in untreated malignant tumours. GST isoenzyme patterns were identical in benign tumours and malignant tumours before and after platinum/cyclophosphamide chemotherapy, while GST pi was the predominant transferase. Mean GST activity and GST pi amount were decreased (P < 0.05) in malignant ovarian tumours after platinum/cyclophosphamide chemotherapy compared to untreated ovarian malignant tumours. No relation was found in untreated ovarian tumours between GST pi amount and response to platinum/cyclophosphamide chemotherapy. Thus, within the limitations of the current study no arguments were found for a role of GST in in vivo drug resistance of malignant ovarian tumours to platinum/cyclophosphamide chemotherapy.

Adenocarcinoma↗
PubMed1991

P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy.

P-glycoprotein (P-gp) expression and DNA topoisomerase (Topo) II are important variables in multidrug resistant tumor cell lines. The aim of this study was to evaluate P-gp expression and Topo I and II activity in benign and malignant epithelial ovarian tumors. P-gp expression was analyzed immunohistochemically in cryostat sections of fresh tumor specimens. In the same specimens Topo I and II activity were measured by, respectively, relaxation of supercoiled plasmid pBR322 DNA and decatenation of kinetoplast DNA. P-gp expression (range, 5-100% positive staining cells) was found in 3 of 6 cystadenomas, 0 of 2 borderline tumors, 15 of 21 untreated ovarian cancers, and 8 of 13 platinum/cyclophosphamide treated ovarian cancers. Median Topo I and II activity were elevated in malignant ovarian tumors compared to benign and borderline tumors. No difference was found between median Topo I activity in untreated ovarian cancer and platinum/cyclophosphamide treated ovarian cancer. High Topo II activity (greater than or equal to 8 x 10(2) units/mg protein) was more frequent in untreated compared to platinum/cyclophosphamide treated samples. Respectively, 8- and 16-fold differences in Topo I and II activity were found in the malignant tumors. Topo II activity in malignant tumors correlated with Topo I activity (r = 0.36, P less than 0.05) and the tumor volume index (r = 0.35, P less than 0.05). However, this last weak correlation cannot explain the 16-fold differences in Topo II activity in malignant tumors. Mitotic index and P-gp expression did not correlate with Topo I or II activity. A large variability in P-gp expression and Topo I and II activity was observed in patients with ovarian cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Small lymphocytic lymphomas with predominant splenomegaly: a comparison of immunophenotypes with cases of predominant lymphadenopathy.

In this study, we compared small lymphocytic lymphomas with predominant lymphadenopathy with those with predominant splenomegaly and found differences in morphology and immunophenotype as well as clinical features. Cases with lymphadenopathy were characterized by widespread disease, CLL type morphology with proliferation centers, and a CD5, CD11c, CD23, CD43 positive, CD45Ro negative immunophenotype. Cases with predominant splenomegaly had more localized disease, a mantle zone pattern or a diffuse growth pattern without proliferation centers, and a CD5, CD11c, CD23, CD43 negative, and sometimes CD45Ro positive immunophenotype. CD45Ro (UCHL1) positivity and alkaline phosphatase staining were associated with a mantle zone growth pattern. Comparison with other small lymphocytic lymphoma subtypes indicated that each has its own specific immunophenotype.

Aged↗
PubMed1990

Cancer of the uterine cervix: sensitivity and specificity of serum squamous cell carcinoma antigen determinations.

Between 1978 and 1989, 451 patients with cervical squamous cell carcinoma were referred to our department, of whom 143 experienced persistent or recurrent disease. Serial serum samples of the patients were analyzed for the presence of squamous cell carcinoma antigen (SCC). The incidence of elevated pretreatment serum SCC levels ranged from 37% in stage IB (N = 173) to 90% in stage IV (N = 19). Multivariate analysis showed that deep stromal infiltration and lymph node metastases were associated with significantly higher serum SCC levels. Serum SCC trends correlated with the course of disease: after treatment the sensitivity (percentage positive results in patients with persistent disease) was 79% and the specificity (percentage negative results in patients with no evidence of disease) was 91%. During follow-up, the sensitivity of the assay was 85.5% in patients with recurrent disease. However, the positive predictive value of a single serum SCC value greater than 2.5 ng/ml for tumor recurrence was only 49%. This figure rose to 76% when two consecutive elevations were determined. Stage and pretreatment serum SCC level were the only factors found to influence survival, using Cox's regression analysis with five pretreatment variables.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Karyotyping and DNA flow cytometry of metastatic ovarian yolk sac tumor.

We karyotyped a metastasis composed of pure yolk sac tumor derived from a primary ovarian germ cell tumor with two components: a dermoid cyst [DNA index (DI) 1.0] and a pure yolk sac tumor (DI 1.88). The metastatic yolk sac tumor had a hypertriploid karyotype and a DI of 1.78 and lacked the germ cell tumor marker i(12p). The absence of this marker in a metastasis from a tumor with a dermoid cyst component might be indicative for a pathogenesis of the yolk sac tumor similar to that of a dermoid cyst and different from that of dysgerminoma.

Adult↗