H. Kirchner

Prognostic significance of Ki-67 immunostaining in nonmetastatic renal cell carcinoma.

PURPOSE Fresh tissue samples from nonmetastatic renal cell carcinoma (RCC) patients were analyzed by Ki-67 immunostaining to determine the prognostic significance of this tumor-biologic parameter. MATERIALS AND METHODS In a prospective study, Ki-67 immunostaining was performed on frozen sections of histologically proven node-negative RCC from 58 patients operated on between 1986 and 1988 to examine the methods prognostic value and its association with other clinicopathologic parameters such as tumor stage (pT) and grade (G). RESULTS The percentage of Ki-67-positive cells (ie, the proliferation rate [PR]) of all 58 RCC tumors ranged between 1% and 23%, while normal renal tissue exhibited PRs up to 2% only. In almost all cases, the highest PRs were observed in the peripheral zone of malignant tissue close to the normal renal tissue. PR did not correlate with pT, whereas a strongly significant correlation was observed between PR and G, as well as recurrence rate. Twenty-three of 58 patients (39.6%) developed tumor recurrence. Disease-free survival was strongly associated with PR. In a multivariate analysis, G and PR were independent prognostic markers. CONCLUSION The tumor-specific PR obtained by Ki-67 labeling seems to be an independent marker to describe the proliferative activity and aggressiveness of individual tumors. This new tumor-biologic marker detects RCC patients at high risk for recurrent disease, especially in those cases with identical pT and G.

Immunohistological analysis of Hodgkin's and Sternberg-Reed cells: Detection of a new antigen and evidence for selective IgG uptake in the absence of B cell, T cell and histiocytic markers

SummaryTo help clarify the origin and nature of Hodgkins (H) and Sternberg-Reed (SR) cells, three different sets of experiments were performed. First, it was shown that cytoplasmic γ, ϰ, and λ occur not only in H and SR cells, but also in polymorphic tumor cells of epithelial, neurogenic, and lymphoid origin. Furthermore, human IgG that was injected i.v. into rats penetrated many rat liver cells, whereas injected human α1-antitrypsin did not. Second, staining of frozen section revealed that H and SR cells lack surface immunoglobulin and peripheral T-cell antigen. Third, an antiserum raised against the L 428 cell line (derived from Hodgkins disease) and absorbed with human serum and normal cells did not react with any cells of tonsil tissue (lymphoid cells, histiocytes, and interdigitating reticulum cells), whereas it reacted strongly with the L 428 cell line cells and with H and SR cells of 10 different cases. In all ten cases, the antiserum stained the surface of H and SR cells; in two cases, it also stained the nucleoli and some chromatin spots in H and SR cells.The results obtained in these experiments indicate that H and SR cells are not closely related to lymphoid cells, histiocytes, or interdigitating reticulum cells. The findings also suggest that H and SR cells express one or more antigens that have not yet been detected on or in normal cells.

Patient-based strategy for systemic treatment of metastatic renal cell carcinoma

There were only a few options 3 years ago to treat metastatic renal cell carcinoma (mRCC), a disease with a very poor prognosis. With the approval of targeted therapies for mRCC since December 2005, this situation has changed dramatically. Currently, oncologists can choose between several promising options to improve the longevity and quality of their patients’ lives. A widely accepted treatment scheme for targeted therapies in mRCC does not yet exist. Based on a selective literature search, drawing on studies with six targeted therapies for mRCC, and including data from the latest American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) Annual Meetings, this review introduces the available therapies, evaluates patient-specific criteria for their application and suggests an algorithm for a patient-based treatment scheme. Clinical experiences with sequential therapies are summarized and potential combination therapies discussed. In conclusion, the crucial criteria of the treatment scheme we propose are the tumor burden and the disease pace, as well as the quality of life of a patient. These define whether tumor control or tumor remission should be the primary therapeutic goal. This scheme suggests which kind of therapeutic sequence to pursue to optimize patient care in mRCC.

Differenzialtherapie beim metastasierenden Nierenzellkarzinom

ZusammenfassungIm Jahr 2006 wurden Sorafenib und Sunitinib in Europa für die Behandlung von metastasierenden Nierenzellkarzinomen (mNZK) zugelassen. Weitere innovative Substanzen, über die noch keine Daten veröffentlicht wurden, sind auf dem Markt zu erwarten. Sie werden eine ganze Palette individueller therapeutischer Optionen ermöglichen. Die Grundlagen der primären chirurgischen Verfahren zur Tumor- und Metastasenresektion bleiben hierbei unberührt. Da ein anerkannter Algorithmus für diese neue Medikamentenklasse bisher fehlt, werden Empfehlungen zur mNZK-Therapie in der klinischen Praxis notwendig. Der vorgestellte Behandlungsalgorithmus basiert auf Ergebnissen der evidenzbasierten Medizin in Verbindung mit Parametern, die sich aus den im Jahr 2007 beim ASCO-Kongress vorgestellten Daten ergeben haben – und letztendlich auf breiten Erfahrungen bei der Behandlung von mNZK-Patienten.AbstractIn 2006 the new compounds Sorafenib and Sunitinib were approved in Europe for the treatment of advanced renal cell carcinoma (mRCC). Additional innovative substances are to be expected on the market for which data have not yet been published and will provide physicians with a whole array of individual therapeutic options. Principles of primary surgical procedures for tumor and metastasis resection remain untouched. An accepted algorithm for the new drug entities has, however, been missing and it is felt that recommendations on how mRCC should be treated in clinical practice are needed. The suggested treatment algorithm is based on results from evidence-based medicine together with parameters which resulted in the approval of recent data announced at the ASCO congress in 2007 and, last but not least, on wide experience in treating mRCC patients.

Klinische Wertigkeit von In-vitro-Sensitivitätstests

Salmon et al. (1978) haben wesentlich die Entwicklung von In-vitro-Sensitivitatstestverfahren (Soft-Agar-Stammzellverfahren, Human-Tumor-Cloning-Assay (HTCA)) beeinflust. Daraus resultierte die Vorstellung, ein pradiktives Testsystem (sog. Onkobiogramm) zu etablieren, um vor Einleitung einer Chemotherapie bei metastasierten Malignomen die Therapieaussichten abzuschatzen (Von Hoff 1987). Fur das Soft-Agar-Stammzell-Verfahren liegt die groste Erfahrung vor in der Korrelation von In-vitro-Sensitivitatstests und dem Responseverhalten der dazu korrespondierenden Patienten unter Therapie.

The correlation of proliferation rates to prognosis in human renal cell carcinoma

THE FRACTION of proliferating malignant cells strongly influences tumour growth and is believed to be a major parameter for prognosis and treatment selection [I, 2]. Ki-67 immunohistostaining is a practical, reliable and reproducible in situ method of determining individual tumour-specific proliferation rates (PR) directly in human malignancies [I-4]. The monoclonal antibody Ki-67 was first isolated and characterised by Gerdes and colleagues in 1983 [5]. Ki-67 binds to a human nuclear antigen which is only expressed in the Gl, S, G2 and M phases of normal and malignant proliferating cells, but is absent in resting cells (Go) [6]. Several studies on breast cancer and lung cancer have reported an additional prognostic value of this new tumour biological parameter in comparison to conventional parameters (staging, grading, lymph node status) [2-4, 7]. There are no data available comparing tumour-specific proliferation rates and prognosis in human renal cell carcinoma (RCC). Since 1986, in a prospective ongoing study, in vivo proliferation rates in RCC patients were immunohistochemically determined using the Ki-67 assay. All patients entering the study had no evidence of metastatic disease at the time of nephrectomy (according to imaging techniques). Depending on the individual tumour size, several tissue samples are necessary to detect the intratumoral variability [8]. The immunostaining technique for Ki-67 and the evaluation of the slides are described in detail in other reports [I, 7, 9]. Statistical analysis was accomplished using the ×2 test. P values of less than 0.05 were considered significant [9]. The tumour-specific proliferation rates (PR = percentage of Ki-67 positive cells) ranged between I and 23%, whereas normal renal tissue exhibited PR up to 2% only. No correlation between individual PR and tumour stage (pT) was found. However, a strong correlation between PR and low grade (GI) as well as high grade (G3) tumours was observed. These results have previously been published [8] and correspond to other studies on proliferation rates in different human malignancies [2-4, 7].

Outpatient Therapy of Advanced Malignancies Using Recombinant Interleukin-2 and Recombinant Interferon-α With or Without Chemotherapy

The use of recombinant human cytokines has yielded promising results in the treatment of advanced-stage tumor patients for whom no standard therapy is available. In metastatic renal cell carcinoma, objective remissions were reported in patients who had received high-dose intravenous bolus recombinant interleukin-2 (rIL-2) in conjunction with autologous lymphokine-activated killer cells [1]. In this and subsequent clinical trials, however, the severity of adverse reactions (life-threatening fluid retention, hypotension, and pulmonary edema) has limited the intravenous use of rIL-2 to the inpatient and/or intensive care setting, depending on the schedule used [1–6].