Can immunohistochemical markers and mitotic rate improve prognostic precision in patients with primary melanoma?

Ostmeier, H.; Fuchs, Blandine; Otto, F.; Mawick, R; Lippold, A.; Krieg, V.; Suter, L.

doi:10.1002/(sici)1097-0142(19990601)85:11<2391::aid-cncr14>3.0.co;2-i

Cited by 74 publications

(67 citation statements)

References 51 publications

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“…An additional interesting observation in our study was the finding that despite the relatively high mitotic figure count (mean 6.5/mm 2 for all cases) and the relatively large size of these lesions (mean tumor thickness: 20.9 mm), ulceration was a relatively rare event compared with conventional nodular melanomas with similar size and mitotic figure count. [58][59][60][61] This observation may be attributable to the fact that many of our lesions arose in the deep dermis/ subcutis, supporting the concept that ulceration is likely related to the relationship/proximity of the lesion to the epidermis. Alternatively, recent gene expression profiling studies have shown that ulcerated primary melanomas have distinct gene expression profiles compared with their nonulcerated counterparts, suggesting that ulceration may in fact be driven by properties intrinsic to the tumor.…”

Section: Discussionsupporting

confidence: 66%

Melanoma arising in association with blue nevus: a clinical and pathologic study of 24 cases and comprehensive review of the literature

et al. 2014

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Melanomas arising in association with blue nevi or mimicking cellular blue nevi comprise a relatively rare and heterogeneous group of melanomas. It remains controversial which prognostic indicators predictive of outcome in conventional cutaneous melanomas are applicable to this type of melanoma. Here, we describe the clinical and histopathologic features of 24 melanomas arising in association with blue nevi and correlate these with clinical outcome. The mean patient age was 49 years (range: 23-85) with a slight female predominance (15 females:9 males). The most common anatomic locations included the head and neck region (50%), the trunk (21%), and the buttock/sacrococcygeum (17%). Histologically, the tumors were typically situated in the mid to deep dermis with variable involvement of the subcutis, but uniformly lacked a prominent intraepithelial component. The mean tumor thickness (defined as either the standard Breslow thickness or, if not available due to the lack of orientation or lack of epidermis, the largest tumor dimension) was 20.9 mm (range: 0.6-130 mm). The mean mitotic figure count was 6.5/mm 2 (range: 1-30/mm 2 ). Perineural invasion was common (38%). Followup was available for 21 cases (median 2.1 years). The median overall survival, recurrence-free survival, time to local recurrence, and time to distant recurrence were 5.2, 0.7, 2.6, and 1.6 years, respectively. Logistic regression analyses demonstrated a significant association between tumor thickness and recurrence-free survival (hazard ratio ¼ 1.02 per mm; P ¼ 0.04) and reduced time to distant metastasis (hazard ratio ¼ 1.03 per mm; P ¼ 0.02) with a similar trend toward reduced time to local recurrence (hazard ratio ¼ 1.02 per mm; P ¼ 0.07). No other parameters (age, anatomic location, mitotic figures, lymphovascular or perineural invasion, or type of associated blue nevus) emerged as significant. In addition, we provide a comprehensive review of 109 cases of melanoma blue nevus type described in the English literature and summarize our findings in this context.

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Section: Discussionsupporting

confidence: 66%

Melanoma arising in association with blue nevus: a clinical and pathologic study of 24 cases and comprehensive review of the literature

et al. 2014

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“…A German study of 691 patients by Ostmeier et al 19 (Table 3) found that ulceration no longer demonstrated independent significance when TMR was included in their prognostic model. They cited reasons similar to those proposed by Barnhill et al 18 for conflicting results from multivariate analyses.…”

Section: Discussionmentioning

confidence: 99%

Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma

Azzola

Shaw

Thompson

et al. 2003

Cancer

381

217

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BACKGROUNDThe current study was performed to determine whether tumor mitotic rate (TMR) is a useful, independent prognostic factor in patients with localized cutaneous melanoma.METHODSFrom the Sydney Melanoma Unit database, 3661 patients with complete clinical information and details of primary tumor thickness, ulcerative state, and TMR were studied. TMR was expressed as mitoses per mm2 in the dermal part of the tumor in which most mitoses were seen, as recommended in the 1982 revision of the 1972 Sydney classification of malignant melanoma. To determine which was the more prognostically useful method of grouping TMR, two separate methods (A and B) were used. Factors predicting melanoma‐specific survival were analyzed using the Cox proportional hazards regression model.RESULTSPatients with a TMR of 0 mitoses/mm2 had a significantly better survival than those with 1 mitosis/mm2 (P < 0.0001) but no significant survival differences were recorded for the stepwise increases from 1–2, 2–3, 3–4, and 4–5/mm2. Tumor thickness, ulceration, and TMR were closely correlated, whether TMR was grouped using Method A (0, 1–4, 5–10, and ≥ 11 mitoses/mm2) or Method B (0–1, 2–4, and ≥ 5 mitoses/mm2). However, Cox regression analysis indicated that the TMR was a highly significant independent prognostic factor, particularly when grouped according to Method A, in which it was second only to tumor thickness as the most powerful predictor of survival (P < 0.0001).CONCLUSIONSTMR is an important independent predictor of survival for melanoma patients. If confirmed by studies from other centers, it has the potential to further improve the accuracy of melanoma staging, as well as to define more rigidly the risk categories for patients entering clinical trials. Cancer 2003;97:1488–98. © 2003 American Cancer Society.DOI 10.1002/cncr.11196

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“…Although MHC class II presentation of tumor Ags by melanoma cells has been described (14), MHC class II expression was shown to be associated with a better progression of primary melanoma and a higher metastatic dissemination (15). MHC class II constitutive expression in melanomas is considered nowadays as a progression marker (16,17). Therefore, it was proposed that MHC class IIexpressing tumors might mimic an APC and induce lymphocyte anergy by the lack of accessory signals (18).…”

Section: More Recently Attention Has Focused On the Role Of Cd4mentioning

confidence: 99%

Constitutive Expression of MHC Class II Genes in Melanoma Cell Lines Results from the Transcription of Class II Transactivator Abnormally Initiated from Its B Cell-Specific Promoter

Deffrennes

Vedrenne

Stolzenberg

et al. 2001

The Journal of Immunology

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In melanoma cell lines, two different patterns of MHC class II expression have been described, either an IFN γ-inducible expression of HLA-DR and HLA-DP, with a faint or null expression of HLA-DQ, resembling that described for melanocytes, or a constitutive expression, i.e., IFN-γ independent, of all three HLA-D isotypes. As this latter phenotype has been associated with a more rapid progression of melanoma tumors, we have analyzed in different melanoma cell lines the molecular mechanisms leading to this abnormal pattern of MHC class II expression. In agreement with the evidence of a coordinate transcription of the HLA-D genes in these cell lines, we have shown the constitutive expression of CIITA (class II transactivator) transcripts, CIITA being known as the master switch of MHC class II expression. Unexpectedly, these transcripts initiate from promoter III of the CIITA gene, a promoter that is mainly used constitutively in B lymphocytes. This expression was further shown to occur through factor(s) acting on the enhancer located upstream of CIITA promoter III, which was previously described in epithelioid cells as an IFN-γ-response sequence. The hypothesis of a general abnormality of the IFN-γ transduction pathway was dismissed. Constitutive transcription of CIITA from promoter III having been observed in unrelated melanoma cell lines, we propose the hypothesis that this phenomenon might not be a random event, but could be linked to the neoplasic state of the melanoma cells.

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Can immunohistochemical markers and mitotic rate improve prognostic precision in patients with primary melanoma?

Cited by 74 publications

References 51 publications

Melanoma arising in association with blue nevus: a clinical and pathologic study of 24 cases and comprehensive review of the literature

Melanoma arising in association with blue nevus: a clinical and pathologic study of 24 cases and comprehensive review of the literature

Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma

Constitutive Expression of MHC Class II Genes in Melanoma Cell Lines Results from the Transcription of Class II Transactivator Abnormally Initiated from Its B Cell-Specific Promoter

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