Gun Forsslund

Prognostic significance of the DNA content in renal cell carcinoma.

The DNA content in renal cell carcinoma as an indicator of prognosis was studied retrospectively in 55 patients without distant metastases at operation. Two groups of patients were selected, differing with respect to survival. Thirty-three patients survived for at least 10 years and 22 succumbed to the disease within four years. DNA measurements in morphologically identified tumor cells were performed in histological sections by single cell cytophotometry. The tumor cells of the surviving patients had a DNA content comparable to that of normal cells. A diploid/near diploid DNA content was the dominant feature in 32 of these 33 tumors. The remaining patient had a tumor with a tetraploid/near tetraploid DNA value. In contrast, all tumors from the non-surviving patients had abnormally increased DNA content, indicating a high degree of aneuploidy in these tumors. The results suggest that DNA content may be superior to other clinical and microscopical parameters as a prognostic indicator.

The prognostic significance of nuclear DNA content in prostatic carcinoma

The prognostic significance of ploidy level was studied in prostatic carcinoma and compared with the prognostic significance of morphologic grade and clinical stage. A nonselected group of 145 patients was studied in whom prostatic carcinoma was diagnosed by fine‐needle aspiration biopsy at the Karolinska Hospital in 1966. All patients had endocrine therapy and were observed for 23 years or until death. Ploidy level was determined from cytophotometric measurements of Feulgen‐stained tumor cell nuclei. The original May‐Grünwald‐Giemsastained cytologic slides, on which the cancer diagnoses were based in 1966, were destained and subsequently Feulgen stained for cytophotometric analysis. From the Feulgen‐DNA data, the tumors were classified as near‐diploid, near‐tetraploid, and highly aneuploid, variants D‐type, T‐type, and A‐type, respectively. The A‐type tumors progressed rapidly, and 96% of the patients with this type died of the tumor within 5 years and all patients with this type died within 7 years. D‐type and T‐type tumors progressed much more slowly. None of the patients with these types of tumors died of the tumor disease within the first 5 years after diagnosis. As many as 12% of the patients (crude survival rate; corresponding to a relative survival rate of 43%) were still alive 15 years after diagnosis. According to multivariate Cox regression analysis, ploidy compared with grade and tumor stage was the strongest predictor of survival. Cancer 1992; 69:1432‐1439.

Near tetraploid prostate carcinoma. Methodologic and prognostic aspects.

The clinical value of DNA ploidy analysis in prostate carcinoma has been an issue for investigation for more than 2 decades. In general, diploid or pseudodiploid tumors are associated with a favorable prognosis and aneuploid tumors with an unfavorable prognosis, irrespective of type of treatment. Tumors with DNA values in the tetraploid region (around 4c) present a diagnostic problem. Such DNA distributions may clearly represent aneuploid tumors with an unfavorable prognosis. However, a 4c distribution may conversely represent a tetraploid tumor (possibly a polyploid variant of the diploid tumor) with a favorable prognosis. Previous data from our laboratory indicate the existence of such a tetraploid subgroup. The goal of the current study was to investigate the diagnostic problem of 4c tumors in greater detail.

Combined morphologic and cytochemical grading of serous ovarian tumors

The potentiality of DNA analysis to complement morphologic evaluation in classifying serous ovarian tumors as adenoma, borderline malignancy, or invasive adenocarcinoma was investigated in a series of 54 tumors. The DNA analyses were performed on histologic tumor sections. The primary diagnoses were borderline tumor in 24 cases and invasive adenocarcinoma in 30 (World Health Organization classification). When the specimens were reviewed, 17 of the 54 tumors were reclassified, after which the series consisted of 9 adenomas, 24 borderline tumors, and 21 invasive adenocarcinomas. Rising histologic malignancy grade was associated with increasing numbers of cells showing high DNA content. The DNA levels in the adenomas thus were within the diploid range of a normal cell population. They were somewhat higher in the borderline tumors and were highest in the invasive adenocarcinomas. Though no clear-cut intergroup demarcation was discernible, there was a subgroup of adenocarcinomas with greatly elevated DNA levels, indicating high biologic malignancy. The observations suggested that DNA analyses can complement histologic malignancy grading and can be useful for the recognition or highly malignant tumors among invasive adenocarcinomas.

Prognostic significance of nuclear DNA analysis in histological sections in mammary carcinoma.

The nuclear DNA content in tumor cells from invasive ductal breast carcinomas was analyzed in 26 patients who survived more than 10 years and in 23 patients who died within 2 years after operation. The DNA content of individual tumor cells was measured in sections from the originally paraffin-embedded specimens. In short-term survivors, a large proportion of cells with very high DNA values was found in all tumors except one. Only two patients of the long-term survivors had tumors that exhibited such high DNA values. Prognostic information obtained by DNA analysis compared with histologic malignancy grading showed that the specificity using DNA analysis was distinctly higher. The data thus suggest that analysis of DNA content of tumor cells in breast adenocarcinomas can be a useful supplement to histologic malignancy grading to obtain prognostic guidance in individual patients.

Prognostic impact of nuclear DNA content in medullary thyroid carcinoma; a retrospective pilot study

The prognostic significance of DNA content in medullary thyroid carcinoma was studied retrospectively in 16 patients. Five patients died within 3 years of medullary thyroid carcinoma and 11 patients survived for at least 10 years. Clinical data and tumour morphology were studied. DNA measurements on tumour cells in histologic sections were performed with slide cytophotometric technique. The tumours of the survivors had in all but two cases a DNA content comparable to that of normal cells, whereas the tumours of the non-survivors and two of the survivors had higher DNA content. The results indicate that DNA measurements in medullary thyroid carcinoma might be of use in addition to clinical and morphologic data and that further studies are warranted.