Biomedical subjects

P Rudolph

Publications and source records attributed to P Rudolph.

At least 55 records · Page 3Linked to original sources

PubMed1999

Proliferation marker Ki-S11--a prognostic indicator for squamous cell carcinoma of the hypopharynx.

As a potential prognostic factor, the proliferative activity of 131 squamous cell carcinomas (SCC) of the hypopharynx and 47 of their cervical lymph-node metastases was analyzed retrospectively by means of monoclonal antibody Ki-S11 immunostaining, which specifically detects the Ki-67 antigen on paraffin-embedded tissue. Median follow-up time was 37.6 months. Ki-S11 revealed distinctive patterns of proliferating cells related to the degree of differentiation. The proliferation fractions in the primaries and their lymph-node metastases did not differ significantly. Patients with high proliferating hypopharynx carcinomas (>45% labeled cells) had a significantly lower 5-year-survival rate (16%) than patients with low proliferating tumors, whose 5-year-survival rate was 30% (P=0.01). A statistically significant positive correlation was also observed between proliferative activity and lymph-node status (P=0.012). In conclusion, the proliferative activity as determined by means of Ki-S11 immunostaining is of prognostic value with respect to both survival and metastatic risk in SCC of the hypopharynx.

Adult↗

PubMed1999

Ki-A10, a germ cell nuclear antigen retained in a subset of germ cell-derived tumors.

Monoclonal antibody Ki-A10 recognizes a nuclear antigen of 25 and 22 kd apparent molecular mass, which is abundantly expressed by immature gonocytes, spermatogonia, and spermatocytes, whereas it is absent in spermatids, spermatozoa, oocytes, and normal somatic tissues. In a broad spectrum of human cancers the antibody showed no reactivity except for a small subset of malignant lymphomas. Because of this restricted expression pattern, we examined 173 germ cell tumors and 18 sex cord stromal tumors immunohistochemically to assess the distribution of the Ki-A10 antigen. A strongly positive reaction was found in classic seminomas, dysgerminomas, spermatocytic seminomas, and the germ cell component of gonadoblastomas. Yolk sac tumors presented a heterogeneous reactivity pattern ranging from overall positivity to complete lack of antigen expression, and in three of eight choriocarcinomas, a few clusters of cytotrophoblast cells were strongly labeled. All other tumors, including Leydig and Sertoli cell tumors as well as placental tissue, were negative. Our findings suggest that specific germ cell antigens can be retained in germ cell tumors along particular differentiation pathways. Ki-A10 is the first marker that consistently labels spermatocytic seminoma, further confirming its germ cell origin and suggesting a close relationship to classic seminoma. The antibody may serve for diagnostic purposes and promises new insights into the process of germ cell differentiation and the development of germ cell-derived neoplasia.

Animals↗

PubMed1999

Prognostic significance of a novel proliferation marker, anti-repp 86, for endometrial carcinoma: a multivariate study.

Traditional prognostic factors often fail to identify a subgroup of endometrial carcinoma (EC) patients with an apparently paradoxical poor outcome. We therefore analyzed tumor cell proliferation immunohistochemically in a series of 164 endometrial carcinomas (EC) and compared its prognostic impact with that of the standard prognostic factors patient age, FIGO stage, FIGO grading, and histopathologic subtype. In addition to the established proliferation markers Ki-S5 (Ki-67) and KiS4 (topoisomerase IIalpha), we used a novel monoclonal antibody (MAb), anti-repp 86, which binds to a recently described proliferation-specific protein (p86) expressed exclusively in the S, G2, and M phases of the cell cycle. anti-repp 86, Ki-S4, and Ki-S5 immunoreactive labeling indices (LI) correlated significantly with FIGO stage, FIGO grade, and myometrial invasion, but not with histopathologic subtype. By univariate analysis, conventional prognostic factors and proliferation indices were all predictive of disease-related mortality. A multivariate Cox regression analysis selected anti-repp 86 LI (P = .002), FIGO stage (P = .02), and histopathologic type as significant prognosticators of recurrence; anti-repp 86 LI (P = .001) and histopathologic type (P = .0106) also emerged as relevant predictors of mortality. A hierarchical forward regression model with the conventional prognosticators entered first and with anti-repp 86 entered next showed that anti-repp 86 and histopathologic subtype were the superior independent prognostic indicators for an increased risk of recurrence and cancer-related death. We conclude that the evaluation of anti-repp 86 immunostaining is an easily performable and exceptionally reliable method for identifying EC patients with adverse prognosis.

Adult↗

PubMed1999

Prognostic significance of Ki-67 and topoisomerase IIalpha expression in infiltrating ductal carcinoma of the breast. A multivariate analysis of 863 cases.

To evaluate the prognostic relevance of Ki-67 and topoisomerase IIalpha expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki-S11 (Ki-67) and Ki-S4 (topoisomerase IIalpha). pS2, c-erbB2, and p53 were additionally considered as prognostic variables. The median follow-up time was 149 months. Eight-hundred-and-sixty-three tumors reacted with Ki-S11 and Ki-S4; the labeling indices of the two antigens were closely associated (r = 0.93). Both correlated positively with the tumor size, c-erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki-S11 and Ki-S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis-free survival (p < 0.00001). Estrogen receptor status, p53, and c-erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki-S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki-S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki-S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIalpha expression as assessed by monoclonal antibody Ki-S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.

Adult↗

PubMed1999

Differential expression of CD34 and Ki-M1p in pleomorphic fibroma and dermatofibroma with monster cells.

Pleomorphic fibroma (PF) and dermatofibroma with monster cells (DFMC) are characterized by the presence of numerous cells with large atypical nuclei. Despite cytologic similarities, the two entities are likely to be unrelated, but their histogenesis is poorly understood. In this study, we examined six cases of PF and eleven cases of DFMC by immunohistochemistry using antibodies against vimentin, alpha-smooth muscle actin, S-100 protein, CD34, factor XIIIa, and the pan-monocytic marker Ki-M1p. Strong vimentin expression was seen in all tumors, whereas none of them expressed S-100 protein. PF consistently exhibited CD34 staining but appeared to be depleted of Ki-M1p positive cells compared with the surrounding normal skin. Conversely, all cases of DFMC contained numerous Ki-M1p positive cells including atypical multinucleate cells, but virtually no CD34 reactivity was observed. A weak staining for alpha-smooth muscle actin was occasionally seen in a subset of the cells of both entities. Our results indicate that PF and DFMC are histogenetically distinct entities that may arise from two different types of dermal dendritic cells defined by their reactivity for CD34 and Ki-M1p, respectively. Immunohistochemistry using these two antibodies permits an easy and reliable discrimination between PF and DFMC.

Actins↗

PubMed1999

Prognostic significance of serum S100B detection compared with routine blood parameters in advanced metastatic melanoma patients.

Recent reports on the use of a quantitative measurement of S100B protein for the detection of metastatic melanoma have yielded promising results. In this study we evaluated 489 serum samples from 64 patients suffering from advanced melanoma (UICC/AJCC stage IV) to compare the sensitivity of a S100B immunoradiometric assay (IRMA) with that of conventional blood parameters as well as other known clinical prognostic factors. In a univariate statistical analysis, gender, bone metastasis, and lactate dehydrogenase and S100B levels in serum samples were found to be significant prognostic markers (P<0.05). The S100B level represented the only relevant independent prognostic marker that was sustained in a multivariate analysis (P = 0.016). Furthermore, we were able to demonstrate that S100B is of relevance irrespective of the specific sites of metastatic involvement. The other laboratory parameters could not match the sensitivity rate of S100B. Overall survival rate was strongly associated with serum S100B values. The results of our study suggest that S100B might be a useful tool as a melanoma marker and an independent prognostic factor in advanced metastatic melanoma. S100B serum detection is likely to be of great interest for the pretreatment stratification and/or monitoring of patients enrolled in clinical studies.

Blood Platelets↗

PubMed1999

Primary renal malignant fibrous histiocytoma: case report.

We report on a case of primary renal malignant fibrous histiocytoma. Primary manifestation in the kidney is rare with only 22 cases reported in the literature. Preoperatively, a renal cell carcinoma cannot be distinguished from a malignant mesenchymal tumor with clinical or imaging techniques. We discuss the pathologic differential diagnosis, therapeutic strategies and prognosis of this infrequent tumor.

Histiocytoma, Benign Fibrous↗

PubMed1998

[Explant test with skin and peritoneum of the neonatal rat as a predictive test of tolerance of local anti-infective agents in wounds and body cavities].

In vitro culture of peritoneal explants of neonatal rats after previous application of agents simulating wound antisepsis is a sensitive screening method for the determination of the tissue compatibility of local wound antiinfectives. Two test models are differentiated: (1) separated peritoneal explants as a model for chronic or deep wounds and (2) peritoneum in situ in the experimental animal with subsequent extraction and cultivation of the explants. Considering the present state of knowledge the following conclusions can be drawn regarding antisepsis of wounds: Lavasept (0.1%) may be classified as the agent of choice for deep and chronic wounds, for drip-suck irrigation and for antiinfective lavage of body cavities inclusively for peritoneal lavage (0.05%). Taurolidin is antiseptically effective in long term application (> 6 h), and because of its antitoxic effect as well as lack of cytotoxicity it is especially suitable for peritoneal lavage. Betaisodona solution is very well suited for superficial contaminated wounds and can be used in a dilution of 1:10 for short-term rinsing of deep wounds, including body cavities but not for peritoneal lavage. Ethanol causes no inhibition of explant growth and therefore retains its importance in wound antisepsis.

Administration, Topical↗

PubMed1998

Enhanced expression of Ki-67, topoisomerase IIalpha, PCNA, p53 and p21WAF1/Cip1 reflecting proliferation and repair activity in UV-irradiated melanocytic nevi.

To investigate the effect of ultraviolet (UV) irradiation on the expression of cell cycle-associated proteins, melanocytic nevi from healthy volunteers were partially covered, irradiated with a defined UV dose, and excised 1 week thereafter. The irradiated and the protected parts were examined separately by conventional microscopy and immunohistochemistry using the antibodies Ki-S11 (Ki-67), Ki-S7 (topoisomerase IIalpha), PC10 (proliferating cell nuclear antigen [PCNA]), DO-7 (p53), 6B6 (p21WAF1/Cip1), and the melanocytic marker HMB-45. DNA nick-end labeling was used as a marker of apoptosis. Irradiation resulted in morphological changes and increased HMB-45 reactivity. Proliferation, as assessed by Ki-67 and topoisomerase IIalpha expression, was also clearly enhanced in the UV-exposed areas. This was confirmed by the appearance of occasional mitotic figures. PCNA expression levels markedly exceeded those of the proliferation markers and did not correlate with the latter in most cases. p21 immunolabeling indices were also consistently augmented after UV exposure; hence it is likely that growth-inhibitory mechanisms partly compensate for the proliferative impulse, and the disproportional rise in PCNA expression probably reflects DNA repair activity. Enhanced p53 immunostaining in four cases suggests that the induction of p21 after irradiation may be p53 mediated, whereas no concomitant apoptotic events were observed. We conclude that UV light can stimulate the proliferative activity of melanocytes in melanocytic nevi, but that simultaneously cell cycle inhibitors are activated to permit DNA repair.

Adult↗

PubMed1998

Correlation between mitotic and Ki-67 labeling indices in paraffin-embedded carcinoma specimens.

The mitotic index (MI) and the Ki-67 labeling index (LI) are both understood to measure cellular proliferation, but their relationship is poorly defined. We determined the mitotic index in hematoxylin and eosin-stained paraffin sections of 189 consecutive carcinomas and performed immunohistochemistry on sections from the corresponding blocks using the Ki-67-specific monoclonal antibody Ki-S5. The distributions of MI and LI in the entire series were clearly different, the former fitting a Poisson function in contrast to a broad-tailed unspecific distribution of the latter. Both indices were closely correlated in mammary carcinomas and non-small cell lung cancers, and to a slightly lesser extent in colorectal adenocarcinomas. No significant association was found in small cell lung cancers. In squamous cell carcinomas, the two parameters were inversely correlated. A good agreement between MI and LI values was observed in well-differentiated and moderately well-differentiated cancers regardless of their histological type, whereas in poorly differentiated carcinomas the correlation was not significant. We conclude that MI and LI measure different proliferation characteristics. Their relationship appears to depend on the tumor type and the degree of differentiation. Rather than artifacts due to processing or evaluation techniques, specific differences in cell cycle kinetics are likely to account for these discrepancies.

Carcinoma↗

PubMed1998

Immunophenotype, proliferation, DNA ploidy, and biological behavior of gastrointestinal stromal tumors: a multivariate clinicopathologic study.

To determine the prognostic impact of clinical, immunohistochemical, and biological parameters, we examined 52 gastrointestinal stromal tumors (GIST) by conventional light microscopy and immunohistochemistry. DNA ploidy was analyzed by image cytometry on cytospin preparation. The proliferative activity was determined by mitosis counting and assessment of Ki-67 reactivity by means of monoclonal antibody Ki-S5. A histopathologic grade was assigned to each tumor according to the French Federation of Cancer Centers (FNCLCC) grading system. Next to vimentin, CD34 was the most prevalent antigen, followed by markers of neural and muscular differentiation. Many tumors exhibited a mixed phenotype. Twenty-one tumors were diploid, eight hypodiploid, and 23 aneuploid. In univariate analysis, tumor grade, Ki-S5 labeling index, mitotic count, atypical mitoses, cellularity, and sex were predictive of both mortality and metastasis risk. DNA ploidy only correlated with overall survival, whereas the tumor location affected the occurrence of metastases. Multivariate analysis selected Ki-S5 scores (P < .0001) and atypical mitoses (P=.012) as independent prognosticators for overall survival, and tumor grade (P=.0036) and size (P=.0055) as predictors of metastatic spread. We conclude that GIST are primitive mesenchymal tumors capable of divergent differentiation, which does not influence their prognosis. The latter appears to be best predicted by histopathologic grading and the Ki-67 labeling index.

Adult↗

PubMed1998

Scalloped cell xanthogranuloma.

AIMS: We describe nine cases of scalloped cell xanthogranuloma, a distinct solitary variant of non-Langerhans cell histiocytoses. METHODS AND RESULTS: In this retrospective clinicopathological study scalloped cell xanthogranuloma mostly occurred on the back or head and neck of young adult males diagnosed as a xanthogranuloma, naevus, or basal cell carcinoma. Histology characteristically revealed a sheet-like infiltrate of predominantly scalloped histiocytes (> 79% of all cell types) in the upper dermis. Other mononuclear (vacuolated, xanthomatized, spindle-shaped, oncocytic) and multinucleate (foreign body, ground glass and Touton) histiocytes were also regularly seen. Immunohistochemically, all cases exhibited a macrophage/dendritic cell lineage positive with KP1 (CD68), KiM1p, HAM 56 and factor XIIIa. Ultrastructurally, numerous intracytoplasmic dense, occasionally also myeloid bodies were present. No associated systemic disease, hyperlipidaemia or recurrence were seen during follow-up. CONCLUSIONS: These findings are similar to those of early lesions of xanthoma disseminatum: thus, scalloped cell xanthogranuloma could be regarded as a solitary counterpart of xanthoma disseminatum, and, moreover, fits neatly into a unifying concept of non-Langerhans cell histiocytoses.

Adolescent↗

PubMed1998

Giant cell collagenoma: a benign dermal tumor with distinctive multinucleate cells.

We present five cases of a hitherto unreported cutaneous neoplasm. The tumors appeared as solitary slow-growing flesh-colored nodules arising in young and middle-aged adults. They were located on the trunk, the upper extremities, and the face, and did not recur after complete excision. Clinically, they were diagnosed as dermal nevus, Spitz's nevus, fibroma, or neurofibroma. Histology revealed polypoid flat-dome-shaped lesions with a sharply demarcated matrix consisting of coarse hyalinized collagen bundles arranged in a prominent storiform pattern and separated by mucin-containing clefts. Despite a low overall cellularity, the tumors contained numerous, occasionally bizarre-shaped, multinucleate giant cells with crowded vesicular nuclei and a pale staining foamy cytoplasm, as well as plump fibroblastlike cells with analogous nuclear morphology. Atypical nuclei or mitotic figures were not observed. The cells were strongly positive for vimentin but negative for cytokeratin, smooth muscle actin, desmin, S-100 protein, CD34, factor XIIIa, and the macrophage markers KP1, Mac 387, and Ki-M1p, suggesting a fibroblastic origin. Based on the overall architecture, we conclude that these tumors probably represent a distinctive variant of solitary circumscribed storiform collagenoma (sclerotic fibroma) and propose the designation of giant cell collagenoma.

Adult↗

PubMed1998

Asthma and allergies among children in West and East Germany: a comparison between Münster and Greifswald using the ISAAC phase I protocol. International Study of Asthma and Allergies in Childhood.

The study aim was to compare the prevalence of asthma, rhinitis and eczema in children living in Münster, western Germany, and Greifswald, eastern Germany, and to investigate associations of several characteristics and exposures with atopic disease symptoms. In 1994 and 1995, questionnaire information was gathered on 5-8 yr old children (n=3,741 in Münster and n=2,857 in Greifswald) and 12-15 yr olds (n=4,003 and n= 3,153, respectively) using the phase I protocol of the International Study of Asthma and Allergies in Childhood (ISAAC). The 12 month period prevalences of reported atopic disease symptoms in 5-8 yr olds were generally higher in Münster than in Greifswald, whereas only a few prevalence differences were observed in 12-15 yr olds. In both age groups the reported lifetime prevalences of asthma, hay fever and eczema were lower in Greifswald. Indoor exposures such as wood or coal heating and feather bedding were negatively associated with symptoms, whereas exposures such as truck traffic in a residential street or active smoking were positively associated with symptoms. Wood or coal heating could partly explain the prevalence difference of allergic rhinitis symptoms among 5-8 yr olds between Münster and Greifswald. The findings provide additional evidence for a role of several characteristics and exposures as potential determinants of asthma and allergies in children.

Adolescent↗

PubMed1998

Comparative analysis of prognostic indicators for sarcomas of the soft parts and the viscerae.

Purpose of this study was to determine which parameters may be best applied to determine the prognosis of soft tissue and visceral sarcomas, the two groups being regarded as biologically different. In a cohort of 184 soft tissue tumors (STT) and 53 gastrointestinal stromal tumors (GIST), the following factors were examined for their diagnostic and prognostic relevance: patient age, sex, tumor location, histological type, tumor size, tumor grade, DNA ploidy status, mitotic count, and immunohistochemical proliferation index. Tumors were graded according to the FNCLCC system, and antibody Ki-S11 (Ki-67) served as a proliferation marker. Median clinical follow-up time was 48 months. In STT, morphological criteria allowed a ready discrimination between benign and malignant lesions, which was only warranted by histopathological grading in GIST. 178 of all 236 tumors were thus classified as malignant. Whilst most parameters yielded significant results in the univariate analysis, age, sex, and histological type were irrelevant. A proliferation index > 20% predicted a poor outcome in soft tissue sarcomas, in contrast to a threshold of 10% for GIST. In both groups, the Cox multivariate analysis selected the proliferation index as the sole independent predictor of overall survival, whereas it was superseded by the tumor grade with respect to metastatic spread. In conclusion, soft tissue and visceral sarcomas appear to behave basically in a similar manner. Both tumor grade and immunohistochemical proliferation index are of major prognostic value. Concerning the growth fraction, however, different cut-off points should be selected for sarcomas of the soft tissues and those of the digestive tract.

DNA, Neoplasm↗

PubMed1998

[Prognostic factors for gastrointestinal stromal tumors].

AIMS: Stromal tumors of the gastrointestinal tract (GIST) constitute a group of phenotypically heterogenous mesenchymal neoplasms with uncertain biological behaviour. METHODS: We examined 31 cases of paraffin-embedded GIST histologically and immunohistochemically in regard to their proliferation. Mitosis were counted, atypical mitosis were noted. Proliferation was measured immunohistochemically by Ki-S5 expression and cytophotometrically by ploidy. Prognostic factors were evaluated and compared to the clinical behaviour. RESULTS: Mitosis counts with a mean of 6.43/10 HPF (range: 0-51). Eight atypical mitosis were noted of which five had mitosis counts of 10 or less. Proliferation index determined by Ki-S5 was 9.47% (range: 0-30%). Nineteen tumors were aneuploid. Prognostic unfavorable factors included younger age at diagnosis, male sex, muscular differentiation, higher cellularity and site (stomach VS intestine). KAPLAN-MEIER analysis revealed a statistical significance for Ki-S5 index (p = 0.00268) and ploidy (p = 0.0014). Mitosis counts > 10/10 HPF as well as atypical mitosis were associated with an aggressive biological behaviour. CONCLUSIONS: There are different prognostic factors to determine the prognosis of GISTs., e.g. Ki-S5 index, ploidy, mitosis counts and atypical mitosis. Ki-S5 index seems to be the most reliable.

Antigens, CD↗

PubMed1998

The immunohistochemical marker Ki-S2: cell cycle kinetics and tissue distribution of a novel proliferation-specific antigen.

The monoclonal antibody Ki-S2 binds to a recently characterized proliferation-specific protein, p100. To assess its distribution pattern under physiologic and pathologic conditions, we performed immunohistochemical analyses on an exhaustive spectrum of normal tissues, 624 miscellaneous solid cancers, and 95 hematologic malignancies, and compared the results with Ki-67 immunostaining on consecutive sections. In addition, Ki-S2 expression was related to the DNA content by dual parameter flow cytometric analysis in parallel with Ki-67 labeling using a human cancer cell line. Immunoreactivity was enhanced at the G1/S transition and persisted through G2 and M phase. After adequate antigen retrieval, the antibody was found to yield identical results on fresh and formalin-fixed, paraffin-embedded material. The antibody specifically labeled actively proliferating cells, which constitute a subset of the population recognized by Ki-67. In normal human tissues, Ki-S2 immunolabeling hardly ever exceeded 40% of the Ki-67+ cell fraction. Immunoreactive scores of the two antibodies exhibited a linear correlation, but statistically significant differences in the ratio of Ki-S2-positive to Ki-67-positive cells were nevertheless observed between different tissue types. In contrast, the ratio of Ki-S2 and Ki-67 immunoreactive scores varied widely in neoplastic cells and tissues, occasionally attaining a ratio of almost 1:1. This suggests that loss of growth regulatory mechanisms in malignant cells might result in an extreme reduction of the G1 phase fraction and thus in a significantly shorter doubling time. Therefore, antibody Ki-S2 is likely to allow a more precise evaluation of the cell fraction that will complete a division cycle and a more confident appraisal of the malignancy potential of a neoplastic process.

Antibodies, Monoclonal↗

PubMed1997

Proliferation marker Ki-S5 as a diagnostic tool in melanocytic lesions.

BACKGROUND: A discrimination between benign and malignant melanocytic lesions is not always possible by conventional histology. OBJECTIVE: Our purpose was to determine the proliferative activity in various types of melanocytic neoplasms and to appraise its value as a diagnostic adjunct. METHODS: The growth fraction was assessed immunohistochemically in 398 melanocytic lesions by means of the monoclonal antibody Ki-S5 directed to the Ki-67 antigen. In this way, a cut-off level was defined and applied to 112 lesions of equivocal histology. The revised diagnoses were correlated to the clinical courses. RESULTS: Common nevi, Spitz nevi, and melanomas exhibited significantly different proliferation indices and distinctive distribution patterns of cycling cells. In agreement, malignancy diagnosed on the basis of a growth fraction greater than 5% was confirmed by disease progression in 68% of our cases with uncertain diagnosis. CONCLUSION: Determination of the proliferative activity in melanocytic lesions may usefully complement conventional histology to improve diagnostic accuracy.

Antibodies, Monoclonal↗