Nuclear Parameters in the Superficial and Deep Portion of Melanocytic Lesions

Smolle, Josef; Soyer, H. P.; Juettner, F.-M.; Hoedl, Stefan; Kerl, Helmut

doi:10.1016/s0344-0338(88)80120-1

Cited by 28 publications

(15 citation statements)

References 9 publications

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“…In humans, this may contribute to the recognized risk of nevi for progression to melanoma and reports that ∼25% of melanomas arise from a preexisting nevus (14,15). Underscoring the possible link between Wnt and neoplastic progression of nevi, we find that Wnt signaling is preferentially active in the least mature, more proliferative component of the nevus that appears to be of greater malignant potential (43)(44)(45). Recently, we also reported that nevus maturation is associated with marked changes in nuclear chromatin structure (55).…”

Section: Discussionmentioning

confidence: 56%

“…Localization of activated Wnt signaling and expression of cyclin D1 and c-myc was linked to nevus maturation, an important histological parameter, reflected in decreased size and more spindle-shaped morphology of melanocytes deeper within a nevus (Fig. 3B) (43,44). Maturation is associated with enhanced proliferation arrest because nevi can contain some mitotic cells, typically in the least mature upper portion of the nevus (45).…”

Section: Resultsmentioning

confidence: 99%

“…Maturation is associated with enhanced proliferation arrest because nevi can contain some mitotic cells, typically in the least mature upper portion of the nevus (45). Most important, maturation is an indicator of reduced malignant potential (43,44). Although less mature, the upper part of the nevus is judged to be in a senescent-like state, based on widespread expression of p16 (3,12,13) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Wnt signaling potentiates nevogenesis

Pawlikowski

McBryan

Tuyn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway (senescence-associated secretory phenotype). Cellular senescence is also a tumor suppressor mechanism, to which both proliferation arrest and senescence-associated secretory phenotype are thought to contribute. The melanocytes within benign human nevi are a paradigm for tumor-suppressive senescent cells in a premalignant neoplasm. Here a comparison of proliferating and senescent melanocytes and melanoma cell lines by RNA sequencing emphasizes the importance of senescenceassociated proliferation arrest in suppression of transformation. Previous studies showed that activation of the Wnt signaling pathway can delay or bypass senescence. Consistent with this, we present evidence that repression of Wnt signaling contributes to melanocyte senescence in vitro. Surprisingly, Wnt signaling is active in many senescent human melanocytes in nevi, and this is linked to histological indicators of higher proliferative and malignant potential. In a mouse, activated Wnt signaling delays senescenceassociated proliferation arrest to expand the population of senescent oncogene-expressing melanocytes. These results suggest that Wnt signaling can potentiate nevogenesis in vivo by delaying senescence. Further, we suggest that activated Wnt signaling in human nevi undermines senescence-mediated tumor suppression and enhances the probability of malignancy.

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Section: Discussionmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Wnt signaling potentiates nevogenesis

Pawlikowski

McBryan

Tuyn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…These factors together can make it difficult to measure the nuclei in the deep portions in some melanomas. Furthermore, Smolle et al found that the nuclei in the deep portion of melanomas are larger than in the superficial portion (26). If this is true, measuring the cells of the deep portion would be equivalent to measuring the cells with the largest average nuclear size area of the melanoma.…”

Section: Ivlorphometrymentioning

confidence: 99%

Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index in the assessment of proliferative activity and prognosis of primary malignant melanomas of the skin

1996

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Nuclear morphometry, immunohistochemical staining with Ki-67 antibody and mitotic index were studied in primary cutaneous malignant melanomas. The number of Ki-67 positive cells/ 200 tumor cells did not correlate with any nuclear morphometrical parameters, and it only approached but did not reach significant correlation with melanoma thickness according to Breslow. The nuclear area, short axis and long axis correlated with melanoma thickness, but the nuclear axis ratio (which reflects the sphericity of nuclei) and melanoma thickness did not show significant correlation. Mitotic index was higher in thick melanomas and in melanomas with high Ki-67 positivity, large nuclear area, long nuclear short axis, and small nuclear axis ratio. In Cox's stepwise proportional hazard model, melanoma thickness and the nuclear axis ratio were significant independent prognostic factors for patient survival, while the nuclear area, short axis and long axis, gender, age, Clark level, mitotic index and Ki-67 positivity lacked significant independent prognostic value. The results suggest that the proliferative activity of tumor cells does not alone explain the great importance of tumor thickness as prognosticator in melanoma. The thickness of melanoma measured according to Breslow and the nuclear axis ratio are more efficient prognosticators in melanoma than parameters associated with proliferation.

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“…Nuclear size is of particular interest in the diagnosis of neoplasia and grading of malignancy. Cytophotometry and image analysis, addressing measurements of nuclear size, mostly rely on 2-dimensional estimation of nuclear profile areas (32)(33)(34). However, even when supplied by assumptions of nuclear shape, the relationship between nuclear profile areas and true, 3-dimensional nuclear volume is always unknown.…”

Section: Discussionmentioning

confidence: 99%

DNA‐index and stereological estimation of nuclear volume in primary and metastatic malignant melanomas: A comparative study with analysis of heterogeneity

Sørensen¹,

Kristensen

Grymer

et al. 1990

APMIS

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The aim of this study was to investigate the relationship between physical nuclear volume and ploidy level in malignant melanomas, and to analyse the heterogeneity of these two parameters among primary and corresponding secondary tumours. Unbiased stereological estimates of nuclear volume can be obtained objectively by point‐sampled intercepts. Using this approach, the volume‐weighted mean nuclear volume, nuclear v̄v, was estimated in ordinary histological sections from 34 primary cutaneous malignant melanomas and their corresponding 62 metastatic lesions. For comparison, DNA‐indices (DI) were determined by flow cytometry in adjacent sections from the same paraffin‐embedded tumours. Only a poor correlation was found between nuclear v̄v and DI (Kendall's τ=+0.21). The variability of nuclear v̄v among metastatic lesions was increased as compared to primary melanomas, whereas averaged mean values of nuclear v̄v did not differ significantly between the two types of neoplasms. Aneuploidy was not significantly associated with increased nuclear v̄v. Pronounced intra‐patient heterogeneity of nuclear v̄v was disclosed among metastases and between the primary melanoma and the metastatic lesions. Likewise, no significant association between DI of primary and metastatic melanomas was demonstrated. Heterogeneity of nuclear v̄v and DI in malignant melanomas is in agreement with the theory of polyclonality.

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Nuclear Parameters in the Superficial and Deep Portion of Melanocytic Lesions

Cited by 28 publications

References 9 publications

Wnt signaling potentiates nevogenesis

Wnt signaling potentiates nevogenesis

Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index in the assessment of proliferative activity and prognosis of primary malignant melanomas of the skin

DNA‐index and stereological estimation of nuclear volume in primary and metastatic malignant melanomas: A comparative study with analysis of heterogeneity

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