The importance of IL-6 protein expression in primary human renal cell carcinoma: an immunohistochemical study.

AIMS: Interleukin 6 (IL-6) is produced by some renal carcinoma cell lines in vitro. This might be biologically important because IL-6 is a cytokine of particular interest, owing to its involvement in the growth of renal cell carcinoma. In this study, the expression of IL-6 protein in tissue samples from primary renal cell carcinoma was analysed, and then its clinical importance was examined. METHODS: The distribution of IL-6 in renal cell carcinoma was examined by means of an immunohistochemical method in 47 untreated primary renal cell carcinoma samples. The search for a significant difference between histological patterns, Furhman's grading system, TNM classification, and IL-6 protein expression was carried out. RESULTS: Immunohistochemistry demonstrated that IL-6 is expressed in 70% of primary tumours. There was no significant difference in the tumour size and grade between renal cell carcinomas with or without IL-6 expression. However, a relatively large number of high grade tumours expressed IL-6. CONCLUSION: The importance of IL-6 expression with regard to tumour size/local growth is questionable because IL-6 has been correlated with the development of metastatic disease. These data suggest that the production of IL-6 could exert a growth inhibitory effect on primary renal cell carcinoma.

Enhanced expression of interleukin-6 in bone and serum of metastatic renal cell carcinoma.

Interleukin-6 (IL-6) is produced by renal cell carcinoma (RCC) cell lines and primary tumors. Using immunohistochemical staining in two RCC patients with hypercalcemia and high serum levels of free and total IL-6, we showed expression of IL-6 in metastatic bone tissue. The role of IL-6 in hypercalcemia and bone resorption would suggest that bisphosphonates or dexamethasone could be useful as adjuvant therapy for IL-6 dependent bone metastases which fail to respond to interferon alpha (IFN) alpha 2a and all trans retinoic acid (ATRA).

Developmental control of IFN-alpha expression in murine embryos.

The expression of IFN-alpha transcripts was investigated in murine embryos, fetuses, and fetal annexes in mid and late pregnancy. We have shown by Northern blot analysis, reverse transcription-polymerase chain reaction, and in situ hybridization the presence of IFN-alpha transcripts in mouse placenta, fetus, and newborn. From the 14th day of gestation until birth, a typical IFN-alpha transcript (1.2 kb) is found in the fetus. A transcript of larger size (2.2 kb) appears near birth and is present in the newborn mouse. Fetal annexes between the 10th and 21st days of gestation also express IFN-alpha. From the 10th day until birth, the 1.2-kb IFN-alpha mRNA species is present, as well as unusually large transcripts: 4 and 7 kb. To localize IFN-alpha transcripts, in situ hybridization was performed, using 35S-IFN-alpha antisense RNA probe in comparison with the sense RNA probe. The tissue pattern of IFN-alpha transcription in fetuses shows a clear labeling of many epithelia, such as skin, ependyme, and intestine glandular epithelium. A possible relation with cellular differentiation is discussed.

Factors acting upon differentiation of mouse teratoma in vivo: spontaneous differentiation and effects of interferon.

CE/44 mouse teratocarcinoma and its sublines isolated at the Institut Pasteur were studied comparatively in 129/Sv, hybrid F1 129 X NCS, and NCS strains of male and female mice with respect to the age of the animals and the type of the tumor graft (ascitic or subcutaneous solid tumor). The tumors grow more quickly and with more malignant characteristics in female mice. The tumor "takes" and growth are equally good in the hybrid F1 as in 129/Sv mice, but its maintenance in hybrid F1 is not so stable, for a tumor loss and a lessening of differentiation could be seen through the passages in this strain. In the NCS strain the tumor grows very rarely. Interferon slowed the subcutaneous tumor growth and favored neuroepithelial tissue differentiation, but allowed selective growth of one cellular type, the "trophoblastic" one, which is very malignant, and which, in the ascitic tumor, caused death in female animals by a hemorrhagic syndrome.

Ewing's sarcoma: transplantation in nude rat.

Eight Ewing's sarcoma, primary tumor or metastasis, have been transplanted in Nude Rats. These tumors grow slowly and only in female rats. One of them has been maintained for 13 months with 5 passages. It has conserved all the characteristics of the primary tumor, histologic and ultramicroscopic morphology, glycogen secretion and cytogenetic modification (11.22 translocation). The graft of Ewing's sarcoma to Nu/Nu rats is a valuable system to get more material in good condition to study the nature and the origin of Ewing's cells, to test the new chemotherapy trials and to prepare and test the monoclonal antibodies.