DNA aneuploidy and low S-phase fraction as favourable prognostic signs in metastatic melanoma

Muhonen, Timo; Pyrhönen, Seppo; Laasonen, A.; Asko‐Seljavaara, Sirpa; Franssila, Kaarle

doi:10.1038/bjc.1991.392

Cited by 13 publications

(14 citation statements)

References 18 publications

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“…In our primary melanomas S-phase was higher in DNA aneuploid tumours as compared to DNA diploid ones, a result similar to previous findings (Hansson et al, 1982;Muhonen et al, 1991), after measurements on melanoma metastases.…”

Section: Discussionsupporting

confidence: 81%

“…patients with diploid tumours survived longer than those with aneuploid ones. This is also similar to findings with breast cancer (Stal et al, 1991) but in contrast to an earlier study which found that patients with aneuploid melanoma metastases had improved survival (Muhonen et al, 1991).…”

Section: Discussioncontrasting

confidence: 57%

“…In one of them (group A) the patients were given adjuvant chemotherapy when metastases occurred, but not in group B. Muhonen et al (1991) found that patients with aneuploid metastases had improved survival as compared to patients with diploid metastases, indicating better chemotherapy responses in aneuploid cases. This was not corroborated in our study which shows similar survival curves for aneuploid tumours whether given adjuvant chemotherapy or not.…”

Section: Discussionmentioning

confidence: 99%

“…----S-phase <5% S-phase 5.0-9.9% hoim et al, 1990;Wass et al, 1985;Bartkowiak et al, 1991) and of the melanoma metastases in stage III and IV (Hansson et al, 1982;Wass et al, 1985;Muhonen et al, 1991) has earlier been investigated. However, no study has appeared on the prognostic influence of the S-phase and the ploidy as measured on the primary melanoma in patient materials defined by recurrence (stage III).…”

Section: Discussionmentioning

confidence: 99%

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DNA ploidy and S-phase in primary malignant melanoma as prognostic factors for stage III disease

Karlsson

Boeryd²,

Carstensen³

et al. 1993

Br J Cancer

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Summary In 82 patients with stage III malignant melanoma, the primary tumours were investigated by DNA flow cytometry. The tumours were classified as DNA diploid (n = 36), tetraploid (n = l1) and aneuploid (n = 35). By univariate analysis a significant correlation with post-recurrence survival was found for time to first metastasis, DNA-ploidy and S-phase fraction.By multivariate analysis, significant prognostic variables were found to be the time to first metastasis (P = 0.006), and ploidy (P = 0.011). Patients with diploid melanomas and a long recurrence-free interval had a median post-recurrence survival time of 45 months compared to 18 months in patients with DNA aneuploid tumours and an early recurrence.The S-phase could be estimated in 47 primary melanomas and was found to be a significant prognostic variable (P = 0.017). The median survival was 45 months for patients with melanomas with a S-phase fraction below 5%, and 19 months for melanomas with S-phase above 10%. The prognostic value of the S-phase remained significant even after adjustment for recurrence-free interval and DNA ploidy.The prognostic importance of DNA ploidy and S-phase estimated by flow cytometry has been elucidated for a number of different neoplasms (Lenner et al., 1987;Rosenberg et al., 1989;Stal et al., 1989 1966 and 1974. The total follow up period was 7 to 25 years. The mean potential follow up time after recurrence was 12 years and 8 months. There were no significant differences in sex, age, growth pattern, level of invasion, tumour thickness, presence or absence of ulceration and site of origin of the melanoma between the two groups. In group B the time to first metastasis tended to be longer (mean 31.2 months) than in group A (mean 17.5 months), but the difference was not statistically significant (P = 0.054).In group A 12 patients were alive February 1991. Two patients died of squamous cell carcinoma of the lung and duodenal cancer respectively, 10 and 3.5 years after surgery for the primary melanoma. Another patient had a fatal heart infarction 10.5 years after the melanoma diagnosis. These three patients were in complete melanoma remission at death. The other 42 patients in group A had a mean survival of 24.5 months (range 4-68 months) after recurrence, and died with disseminated malignant melanoma. Two patients in group B were still alive February 1991, and in this group four patients died from intercurrent diseases. The 19 patients in group B, who died by dissemination of malignant melanoma had a mean survival time after first metastasis of 20.7 months (range 2-61 months). CytometryAn area with high density of tumour cells was identified on the hematoxylin-eosin stained section and the corresponding area on a 50 gLm section from the formalin fixed paraffinembedded material was identified and deparaffinised in xylene. Hydration was performed in a sequence of ethanol solutions in water (99.5%, 95%, 70% and 40%), and finally the specimens were washed twice with 5-ml aliquots of distilled water. Centrifugations between each...

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Section: Discussionsupporting

confidence: 81%

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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DNA ploidy and S-phase in primary malignant melanoma as prognostic factors for stage III disease

Karlsson

Boeryd²,

Carstensen³

et al. 1993

Br J Cancer

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“…In our previous study on basically the same patient population we observed that DNA aneuploid melanoma patients showed a more favorable prognosis than did DNA diploid patients (8). Furthermore, this difference was more prominent among patients who had received systemic therapy, leading us to the conclusion that DNA aneuploid tumors might be more sensitive to chemotherapy than DNA diploid tumor.…”

Section: Discussionmentioning

confidence: 92%

Mouse Subrenal Capsule Assay Chemosensitivity and DNA Flow Cytometry Parameters of Human Melanoma Metastases

Muhonen

Pyrhönen

Laasonen³

et al. 1994

Acta Oncologica

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Correlation of DNA ploidy and S-phase fraction with chemotherapeutic response and survival in a randomized study of disseminated malignant melanoma

et al. 1996

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"DNA ploidy and S-phase fraction were measured by flow cytometry in the tumour tissue of 87 patients with disseminated malignant melanoma, who had been classified either as responders or with progressive disease in a study of the effects of 2 chemotherapeutic regimens. The patients had been randomized to receive treatment with dacarbazine (DTIC) and vindesine (Eldesine) with or without addition of cisplatin (Platinol). Tumour tissue was obtained from both the primary tumours and the last histologically verified metastases, but in some cases onty the primary tumours or the last metastases could be evaluated. There was a significantly higher mean S-phase value in melanoma metastases from patients with complete or partial responses compared with patients with progressive disease. Neither the S-phase fraction of the primary tumour, nor the DNA ploidy of the primary tumour or of the last histologically verified metastases taken before inclusion into the study were associated with therapeutic response. In the multivariate analysis, both the anatomical location of the metastases and the S-phase fraction measured on the last metastases remained significant prognostic factors of response. In the univariate survival analysis, there was an association between high S-phase fractions of the metastases and longer survival. In the multivariate survival analysis, the S-phase fraction, the number of involved metastatic sites and the treatment response were independent predictive factors. We conclude that, in disseminated melanoma treated with chemotherapy, a high S-phase fraction measured in the last histologically verified metastases is associated with a higher response rate and a longer survival. Our results clearly support the role of S-phase measurement as a potential tool for selecting patients for treatment.o 1996 Wiley-Liss, Inc.Disseminated malignant melanoma is a disease with poor prognosis. The median survival for such paticnts is 5 to I I months, depcnding on the extcnt of the disease. Responses to chemotherapeutic agents are rare, and there is no effective treatment currently available for these patients. Lack of response is therefore a central problem in melanoma chemotherapy, and guidelines are needed for selecting those patients who may possibly benefit from such therapy.It is wcll known that most chemotherapcutic agents act specifically against DNA-replicating cells. DNA flow cytometry can provide information on the ploidy state of a tumour, i.e. the existence of an abnormal cell line, and on the proportion of cells in S-phase, the proliferative phase of the cell cycle. DNA flow-cytometric studies have earlier shown that DNA ploidy and S-phase fraction are important variables in the prediction of survival of patients with cutaneous malignant melanoma (Khcir et al., 1988;Bartkowiak et al., 1991). Results on ploidy have also bccn reportcd in weal melanomas (Karlsson el ul., 1995). The survival of the patients was longer when these melanomas were DNA diploid and had a low S-phase fraction.Some studies on malignancie...

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DNA aneuploidy and low S-phase fraction as favourable prognostic signs in metastatic melanoma

Abstract: (Clark et al., 1969) and thickness of tumour (Breslow, 1970) are known to predict the clinical behaviour of primary melanoma.

Cited by 13 publications

References 18 publications

DNA ploidy and S-phase in primary malignant melanoma as prognostic factors for stage III disease

DNA ploidy and S-phase in primary malignant melanoma as prognostic factors for stage III disease

Mouse Subrenal Capsule Assay Chemosensitivity and DNA Flow Cytometry Parameters of Human Melanoma Metastases

Correlation of DNA ploidy and S-phase fraction with chemotherapeutic response and survival in a randomized study of disseminated malignant melanoma

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