Clinical and Histopathologic Predictors of Survival in Patients With Malignant Melanoma: a Population-Based Study in Sweden

Thörn, Magnus; Pontén, Fredrik; Bergström, Reinhold; Sparén, Pär; Adami, Hans Olov

doi:10.1093/jnci/86.10.761

Cited by 131 publications

(91 citation statements)

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“…Predominantly CD8 þ and CD68 þ cells were detected in the lesions, but only CD68 þ and not CD8 þ infiltrates were positively associated with higher B7-H4 expression ( Table 1). The number of lymphocyte infiltrates has been correlated to patient's survival in some studies (2, 49), but not in others (50,51). Even more important than the frequencies of immune infiltrates is the functionality of the immune cells (52).…”

Section: Discussionmentioning

confidence: 99%

B7-H4 Expression in Human Melanoma: Its Association with Patients' Survival and Antitumor Immune Response

Quandt

Fiedler

Boettcher

et al. 2011

Clinical Cancer Research

129

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Purpose: Cancers have developed a number of strategies to escape immune responses including the differential expression of costimulatory molecules of the B7 family. B7-H3 and B7-H4 have recently been described in different tumor entities but the relevance for melanoma has not yet been studied so far.Experimental Design: Using immunohistochemistry, B7-H3 and B7-H4 expression was studied on 29 melanoma lesions. Survival curves and log-rank tests were used to test the association of protein expression with survival. Cell lines were evaluated for B7-H3 and B7-H4 expression by PCR and flow cytometry. Functional T-cell-tumor coculture assays were carried out with in vitro generated tumor transfectants.Results: B7-H3 and B7-H4 expression was detected in primary tumor lesions (29 of 29 and 28 of 29) and in metastases (28 of 29 and 26 of 29). The numbers of CD68 þ macrophages were significantly lower in patients with low B7-H4 expression, whereas CD8 þ T-cell infiltrates were independent of expression levels.Furthermore, a survival benefit for patients with B7-H4 low expressing melanoma was found, whereas B7-H3 was not associated with any clinical parameter. All 23 melanoma cell lines analyzed expressed B7-H3 and B7-H4 mRNA and protein, but B7-H4 was restricted to intracellular compartments. On silencing of B7-H3 by specific shRNA tumor-associated antigen-specific T cell responses were unaltered. Overexpression of B7-H4 on melanoma cells did not alter the cytotoxicity of different CD8 þ effector cells, but drastically inhibited cytokine production. Conclusions: Our study provides for the first time evidence of B7-H4 expression on melanoma cells as a mechanism controlling tumor immunity which is associated with patients' survival. Clin Cancer Res; 17(10); 3100-11. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

B7-H4 Expression in Human Melanoma: Its Association with Patients' Survival and Antitumor Immune Response

Quandt

Fiedler

Boettcher

et al. 2011

Clinical Cancer Research

129

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“…CMM is known to have a worse prognosis in men Thörn et al, 1994;Smith et al, 1998). Some data also show a sex difference in effectiveness of CMM prevention campaigns.…”

Section: Discussionmentioning

confidence: 99%

Mortality from cutaneous melanoma: evidence for contrasting trends between populations

et al. 2000

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Figure 1Age-adjusted mortality rates for young (30-59) and old (60-79) men and women (world standard population) increases were observed among men. The annual percentage increase in rates for men and women 60-79 years old was, respectively, 12% and 4% in Australia, 7% and 2% in the USA, and 9% and 4% in the Nordic countries. We found a less marked difference between men and women in the CMM mortality increase in Canada (6% for men and 4% for women), Japan (6% and 4%) and the UK (7% and 5%). In France, Italy and Czechoslovakia, CMM mortality rates were low in the 1960s, but afterwards, average annual increases were 24% and 27% in French men and women, 15% and 13% in Italian men and women, and 17% and 33% in Czechoslovakian men and women. Because CMM mortality increased more in older than in younger people, those who died from CMM in 1994 were 10 years older on average than those who died in 1960. Age-period-cohort modelsThe age-period-cohort models yielded drift terms (measures of the average trend over time) that were all positive and in agreement with the annual percentage increases described above. CMM mortality rose linearly during the period of observation in every population. In every country but Japan, the increase was greater (higher drift) for men than for women. The largest sex differences in drift were observed in Australia, Canada and the USA. Consistent with the analysis of the age-standardized rates, the highest values for drift were found in France, Italy and Czechoslovakia.Trends in mortality rates by birth cohort have been derived from the APC model, and are shown in Figure 2 for three selected countries (Australia, UK and France). These countries were chosen because they represented the three CMM mortality patterns that we observed after APC modelling (see below). Each graph contains three plots that described different scenarios: in the upper plot, all the drift is attributed to a birth cohort effect, in the lower plot all the drift is attributed to a period effect. The rates displayed in Figure 2 simply reflect the trend in rates by birth cohort and are therefore not comparable with actual rates observed in populations. If in each scenario rates are decreasing, we can conclude that there is a real decrease. The trends in CMM mortality rates illustrated by these models describe three patterns:1. increasing rates until generations born around [1930][1931][1932][1933][1934][1935] (for Australia increasing rates ceased earlier), followed by decreasing rates in more recent birth cohorts (in Australia, the Nordic countries and the USA) 2. increasing rates until generations born during World War II, followed by flattening or slightly decreasing rates in more recent birth cohorts (UK, Canada) 3. a steep, almost linear, increase with no major change in this trend (France, Czechoslovakia, and Italy).CMM mortality rates in Japan showed a pattern similar to that described in the third group but the rates of increase were much smaller. DISCUSSIONWe have succeeded in identifying meaningful patterns in the g...

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“…10,36,37 It is apparent that the thickness of primary melanoma at time of initial diagnosis shows progressive diminution in nodular vs superficial spreading vs lentigo maligna melanoma. 38 However, our contention is that this reflects reproducible differences in the biology of each process, thus, nodular melanoma, which manifests a vertical growth phase de novo would naturally be expected to have the greatest thickness and also to contain, by definition, a clone or clones of neoplastic cells capable of metastatic progression. In contrast, lentigo maligna melanoma, arising in a lentigo maligna manifesting as a persistent pigmented shows a spindle cell vertical growth phase with wavy or fusiform, hyperchromatic nuclei, mimicking those of Schwann cell derivation.…”

Section: Histologic Type Of Melanomamentioning

confidence: 96%

Prognosticators of melanoma, the melanoma report, and the sentinel lymph node

2006

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Since the 1960s, the clinical characteristics of melanoma, its histopathology and its biological basis have been the subject of intense study at pigmented lesion clinics in North America, Europe, and Australia. More recently, the immense database of the Melanoma Committee of the American Joint Committee on Cancer (AJCC) has been exploited through complex mathematical models to measure the impact of various histologic features of primary melanomas and of sentinel lymph node deposits and to correlate these parameters with patient survival. The wealth of modern information available to pathologists and clinicians has become of vital interest to the prognostication of the individual patient with melanoma. The purpose of this review is to bring to the attention of anatomic pathologists the essential characteristics of the pathology report for primary cutaneous melanoma in the modern era.

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Clinical and Histopathologic Predictors of Survival in Patients With Malignant Melanoma: a Population-Based Study in Sweden

Abstract: The present population-based study identifies independent clinical and histopathologic predictors of survival in cutaneous malignant melanoma and emphasizes the role of histopathologic characteristics such as tumor thickness, ulceration, and vascular invasion besides anatomic site.

Cited by 131 publications

References 0 publications

B7-H4 Expression in Human Melanoma: Its Association with Patients' Survival and Antitumor Immune Response

B7-H4 Expression in Human Melanoma: Its Association with Patients' Survival and Antitumor Immune Response

Mortality from cutaneous melanoma: evidence for contrasting trends between populations

Prognosticators of melanoma, the melanoma report, and the sentinel lymph node

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