Jeanette Philips

INCREASED EXPRESSION OF HLA-DR ANTIGENS ON RENAL TUBULAR CELLS IN RENAL TRANSPLANTS: RELEVANCE TO THE REJECTION RESPONSE

Whether the expression of DR antigens is altered in cadaver renal transplants was examined by the use of monoclonal antibodies to the non-polymorphic region of the DR molecule and an indirect immunoperoxidase stain. Expression of DR antigens increased considerably on renal tubular cells in all 25 biopsy specimens which showed severe cellular rejection, but in only 4 of 14 biopsy specimens with no or minimum evidence of rejection. 2 of these 4 specimens were from patients recently treated for severe rejection and the other 2 subsequently lost their grafts from chronic rejection. DR antigens were also expressed on the cell surface of isolated tubular cells aspirated from transplanted kidneys with acute cellular rejection but not on tubular cells in normal kidneys or aspirates from kidneys without rejection. Biopsy specimens with increased DR expression in tubules usually had an interstitial T cell infiltrate. Expression of DR antigens on tubular cells was not related to HLA-DR incompatibility between donor and host, or to the type of immunosuppressive therapy given. The expression of DR antigens on renal tubular cells may be induced by the infiltrating activated T cells or be a consequence of tubular regeneration following rejection or ischaemic damage. The increased expression of DR antigens on renal tubular cells during rejection makes these cells potential targets for delayed type hypersensitivity responses, which are only effective against DR antigen bearing cells.

Extraskeletal Ewing's sarcoma: A clinical, morphological and ultrastructural analysis of five cases with a review of the literature

In 1969 it was recognised that tumors with light microscopic appearances indistinguishable from Ewings sarcoma of bone may arise in extraskeletal sites (extraskeletal Ewings sarcoma). Here, we review the available literature and report five new cases. All five received combined modality therapy with combination chemotherapy and radiotherapy to the primary site followed by surgical excision in two. All attained complete remission; after a median follow-up of 26 months, three remain disease-free but two have relapsed and died. Our experience, in accord with previous series, suggests that extraskeletal Ewings sarcoma compared with its bony counterpart tends to occur in older subjects, has a similar incidence in males and females, usually presents with a painless mass and readily responds to combined modality therapy. We detected no light or electron microscopic features to denote a histogenetic origin. However, we suspect extraskeletal Ewings sarcoma may occur more frequently than previously supposed.

Measurement of cellular DNA content as an adjunct to diagnostic cytology in malignant effusions

We reviewed the final diagnosis and outcome of 119 patients who developed serous effusions. In addition to routine cytological examination, the cellular DNA content of fluid samples aspirated from the effusions was measured using flow cytometry in order to determine whether the detection of aneuploid cells could aid in diagnosis or serve as a guide to prognosis. The final diagnosis of 35 patients was non-malignant and a further 40 patients with biopsy-proven cancer had cytologically negative effusions. In all of these cases flow cytometry revealed the presence of diploid cells only. The effusions from 36 cancer patients were reported by cytology to contain a variable proportion of malignant cells, and aneuploid cells were detected in 23 of these samples, the remainder containing only diploid cells. Of 8 effusions where cytology was equivocal, one contained aneuploid cells and clinical outcome subsequently showed that all 8 were malignant. Median survival of patients with cancer was 3 months, and a positive cytology had no influence on survival. However, of the patients with positive cytology, those whose effusions contained aneuploid cells had a poorer short-term prognosis than those cases where only diploid cells could be detected (median survival 1.5 vs 4 months). Measurement of cellular DNA content using flow cytometry can occasionally confirm cancer in a cytologically equivocal effusion, but the negative results in 13 out of 36 (36.1%) effusions where cytology was reported as positive suggests that it has only a limited role in this clinical setting, using currently available techniques.

Diagnosis of renal allograft rejection by analysis of fine-needle aspiration biopsy specimens with immunostains and simple cytology.

Fine-needle aspiration biopsy specimens of renal transplants were analysed by means of commercially available monoclonal antibodies and an immunoperoxidase stain. Three cellular features associated with acute cellular rejection were identified--heavy infiltrates of activated T cells or large mononuclear cells strongly expressing HLA-DR antigens, and HLA-DR expression by renal tubular cells. A combination of semiquantitative scores for these features correctly identified rejection in 32 of 34 cases, with no false positives in cases of cyclosporin nephrotoxicity or stable graft function.

Detection of malignant cells in voided urine from patients with bladder cancer, a novel monoclonal assay.

A simple assay is described for detecting malignant cells in the voided urine from patients with transitional cell carcinoma of the bladder. Agarose-embedded urothelial cells from 24 biopsy-proven cancer patients and 10 controls were stained for surface immunofluorescence with four monoclonal antibodies reactive with human bladder cancer and three monoclonals reactive with blood group A. Reactivity was assessed by fluorescence microscopy. One antibody, BLCA-8 appeared to have particular diagnostic utility. Thus, 24.3 +/- 5.8 percent of outer layer and 27.0 +/- 4.6 percent of inner layer urothelial cells reacted with BLCA-8 in patient samples, compared to 2.9 +/- 1.0 and 0.8 +/- 0.5 percent of similar cells from control urines. BLCA-8 antigen expression was found to be relatively stable even after prolonged exposure to urine. In a comparison with conventional cytology, samples from 4/8 patients were considered positive by standard methods, whereas, 8/8 were BLCA-8 positive. This new technique may thus be a useful adjunct to conventional methods.

Characterization of a New Human Bladder Cancer Cell Line, Ucru-BL-28

A new human bladder cancer cell line, UCRU-BL-28 has been established and characterized from a relapsed, cisplatin resistant, grade II, stage T4 tumor. This line is tumorigenic in nude mice and reflects the pathology of the original tumor. The morphology, the expression of tumor-associated antigens and EGF receptors, and the ability to grow both in an anchorage independent manner and in the absence of serum is explored. The BL-28 line has 71-74XXY chromosomes, with del 5q, der(9) and i(19q). Further studies on the molecular basis of bladder cancer, chemosensitivity to cisplatin, growth factor production and tissue invasion are under way.

Percutaneous thoracic aspiration needle biopsies

Summary The results of percutaneous thoracic aspiration needle biopsies in 221 patients performed over a 9‐yr study period are presented. Indication for aspiration was a presumptive clinical diagnosis of primary or metastatic carcinoma of the lung or mediastinum. Of the 221 cases, 135 aspirates were reported as positive for malignancy, 26 were suspicious and 60 were diagnosed as negative or unsatisfactory. Follow‐up data revealed 140 histologically and/or clinically confirmed cases of malignancy; of these 102 had aspirates diagnosed as positive, 15 as suspicious and 23 as negative. This represents a positive tissue diagnosis for malignancy of 73% from a minimally invasive technique within the study period. No false positive diagnoses were made.

Thyroid cancer — Its epidemiology, clinical features and treatment

&NA; Thyroid Cancer – Its Epidemiology, Clinical Features and Treatment. Georg Riccabona. Springer Verlag, Berlin. ISBN 3‐540‐16555‐X, pp. x+ 150, illustrated. Introduction to Hematology. Samuel I. Rapaport. Harper & Row (J. B. Lippincott) ISBN 06‐6510036,0‐397‐50838‐7, pp. vii + 624, illustrated.

Pathology Annual: 1987 Volume 22, Part 1, Paul Peter Rosen, Robert E. Fechner (Eds.). Appleton-Century-Crofts, Norwalk, Connecticut (1987), ISBN 0-8385-7778-4, pp. 388, illustrated.

55.50. Environmental Health Criteria 75. World Health Organization Geneva 1987. ISBN 92‐4‐154275‐6, pp. 3 + 72. Urologic Pathology. Robert O. Petersen. Harper & Row, Publishers. ISBN 06‐6507917, pp. vii+ 762, illustrated. Cancer Risks. Peter Bannasch. Springer GmbH & Co. ISBN 0‐387‐17465‐6, pp. vi+199, illustrated. Clinical Hematology. Mary Louise Turoeon. Oxford University Press. ISBN 0‐316‐85608‐8, pp. vii + 442, illustrated.

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60.00.