DNA content in renal cell carcinoma. A clinical study with special reference to tumor heterogeneity and prognosis.

The prognosis for patients with renal cell carcinoma is difficult to predict. For other malignant tumors, predictions of prognosis have been facilitated by analysis of tumor DNA content. It seemed therefore important to investigate DNA content and its possible prognostic value in renal cell carcinoma. DNA measurements were performed retrospectively on paraffin sections or aspiration biopsy smears by static cytometry. Paraffin-embedded tissues were also analysed, after enzymatic isolation of nuclei, using flow cytometry. Prospective analyses were performed by flow cytometry of fresh tissues. Four different methods for analysis of DNA content were compared in 30 samples: flow cytometry of fresh and paraffin-embedded tissues and static cytometry on imprints and paraffin sections. Comparable results were obtained for all 4 methods (r = 0.744-0.970, p less than 0.001). Histopathologic grade correlated with tumor DNA content. All grade 1 and 81% of grade 2 tumors were diploid. Grade 3 tumors were most common and about 50% of these were aneuploid. 83% of grade 4 tumors had an aneuploid DNA content. By analysis of 8 different samples from each of 25 tumors, a considerable heterogeneity was found in 11 of 13 non-diploid whereas 12 tumors were homogenously diploid. 55 patients without distant metastases at nephrectomy were grouped with respect to survival time. Patients surviving more than 10 years had nearly all diploid tumors (32/33) whereas all 22 patients surviving less than 4 years had aneuploid tumors. For 32 patients with distant metastases, analyzed retrospectively, the survival time was significantly correlated to the DNA content of the metastases. For their primary tumors no such correlation was found, when only one sample was analysed. In contrast, by prospective analysis of multiple samples from the primary tumors of 23 other patients with distant metastases, the DNA content gave important prognostic information. Thus, analysis of multiple samples improved the prognostic information given by the DNA content in primary tumors. The metastases were more frequently aneuploid, as compared to the primary tumors, indicating higher metastatic ability of aneuploid cell populations. Occasionally, in patients with aneuploid cell clones in the primary tumors, metastases with a diploid DNA content were found. The DNA content of the metastases provided additional prognostic information to that obtained from the primary tumors.(ABSTRACT TRUNCATED AT 400 WORDS)