G1 cell cycle regulators in congenital melanocytic nevi. Comparison with acquired nevi and melanomas

Stefanaki, Christina; Stefanaki, Kalliopi; Antoniou, Christina; Argyrakos, Theodoros; Stratigos, Alexander J.; Patereli, Amalia; Katsambas, Andreas

doi:10.1111/j.1600-0560.2007.00912.x

Cited by 26 publications

(19 citation statements)

References 39 publications

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“…Cyclin D1-positive cells were mostly located close to the dermal–epidermal junction, which corresponds to the observations of Stefanaki et al [23] that common nevi shows either rare cyclin D1 positivity or a zonal expression pattern. This is quite distinct from melanomas which display diffuse cyclin D1 expression.…”

Section: Discussionsupporting

confidence: 89%

Cyclin D1 and D3 expression in melanocytic skin lesions

et al. 2010

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Cyclins, cyclin-dependent kinases, as well as proteins cooperating with them are responsible for cell cycle regulation which is crucial for normal development, injury repair, and tumorigenesis. D-type cyclins regulate G1 cell cycle progression by enhancing the activities of cyclin-dependent kinases, and their expression is frequently altered in tumors. Disturbances in cyclin expression were also reported in melanocytic skin lesions. The objective of the study was to evaluate the expression of cyclins D1 and D3 in common, dysplastic, and malignant melanocytic skin lesions. Forty-eight melanocytic skin lesions including common nevi (10), dysplastic nevi (24), and melanomas (14) were diagnosed by dermoscopy and excised. Expression of cyclin D1 and D3 was detected by immunohistochemistry and quantified as percentage of immunostained cell nuclei in each sample. In normal skin, expression of cyclins D1 and D3 was not detected. The mean percentage of cyclin D1-positive nuclei was 7.75% for melanoma samples, 5% for dysplastic nevi samples, and 0.34% for common nevi samples. For cyclin D3, the respective values were 17.8, 6.4, and 1.8%. Statistically significant differences in cyclin D1 expression were observed between melanomas and common nevi as well as between dysplastic and common nevi (p = 0.0001), but not between melanomas and dysplastic nevi. Cyclin D3 expression revealed significant differences between all investigated lesion types (p = 0.0000). The mean cyclin D1 and D3 scores of melanomas with Breslow thickness <1 mm and >1 mm were not significantly different. G1/S abnormalities are crucial for the progression of malignant melanoma, and enhanced cyclin D1 and D3 expression leading to increased melanocyte proliferation is observed in both melanoma and dysplastic nevi. In histopathologically ambiguous cases, lower cyclin D3 expression in dysplastic nevi can be a diagnostic marker for that lesion type.

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Section: Discussionsupporting

confidence: 89%

Cyclin D1 and D3 expression in melanocytic skin lesions

et al. 2010

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“…This result corresponds to documented higher levels of p16 staining in benign [9–13], congenital [14], conjunctival [15], oral [16], and Spitz nevi [17–19], when compared to melanoma. Our study further subclassified lesions based on the level of atypia, and we found a trend towards decreasing p16 staining as the level of atypia increased.…”

Section: Discussionsupporting

confidence: 79%

“…Since loss of p16 expression has been documented to occur in melanoma [8], p16 may be a potential helpful marker in differentiating atypical melanocytic nevi from melanoma. p16 has been shown to be decreased or absent in melanoma compared to benign melanocytic nevi [9–13], including congenital melanocytic nevi [14]. This loss of p16 staining in melanoma compared to benign nevi has also been found to occur in noncutaneous sites such as the oral mucosa and conjunctiva [15, 16].…”

Section: Introductionmentioning

confidence: 99%

p16 Expression Is Lost in Severely Atypical Cellular Blue Nevi and Melanoma Compared to Conventional, Mildly, and Moderately Atypical Cellular Blue Nevi

Chang

Cassarino

2014

ISRN Dermatology

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Background. Significant decreases in p16 expression have been shown to occur in melanoma compared to Spitz tumors, and loss of p16 staining has been found to correlate with melanoma tumor progression. However, comparison of p16 between atypical cellular blue nevi (CBN) and melanoma has not been reported previously. Methods. p16 immunohistochemical staining was evaluated in 14 atypical CBN, 8 conventional and atypical melanocytic nevi, and 16 melanomas, including 4 malignant CBN. p16 staining intensity was graded on a scale of 0–3 and the percentage of melanocytes stained with p16 was determined. Results. p16 staining was significantly higher in all CBN as a group when compared to melanomas (P = 0.001) and malignant CBN (P = 0.00008). Higher p16 expression was also seen in mildly (P = 0.0002) and moderately atypical (P = 0.02), but not severely atypical, CBN compared to melanomas. Conclusions. p16 immunohistochemical expression is higher in mildly and moderately atypical CBN compared to severely atypical CBN and melanomas. In conjunction with additional markers and histology, p16 staining may be useful in confirming the benign nature of these tumors, but is not useful in distinguishing severely atypical CBN from malignant cases, consistent with the overlapping histologic features between these tumors.

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“…The negative cell cycle regulators p16 and p27 were diffusely expressed at high levels in all intramucosal nevi cells, in contrast to oral melanomas, which demonstrated a much lower expression of these proteins. In agreement with these results, cutaneous nevi have been shown to be uniformly positive for p16 in more than 70% of cells [7,15]. On the other hand, loss of p16 expression has also been demonstrated in almost 50% of primary cutaneous and oral melanomas, similarly to many other cancers, including pancreatic, esophageal, lung, head and neck, breast, bladder, brain and ovarian [1,5,13,14].…”

Section: Discussionsupporting

confidence: 70%

“…Among the cell cycle regulators, some studies have focused on the expression of p16, p21, p27 and cyclin D1 in cutaneous melanocytic lesions and melanomas, but little is known of their expression in oral melanoma and there are no data about oral nevi [1,6,7]. These proteins are involved in the retinoblastoma protein (pRb) and p53 pathways.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Andrade

León

Carlos³

et al. 2012

Head and Neck Pathol

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The acquisition of abnormalities at G1/S is considered a crucial step in the genesis and progression of melanoma. The expression of cell cycle regulators has also been used in various neoplasms as an adjunct to diagnosis. The aim of this study was to compare the expression of p16, p21, p27 and cyclin D1 in oral nevi and melanomas. Expression of these cell cycle regulatory proteins was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas. p16 and p27 were highly expressed in intramucosal nevi, whereas p21 and cyclin D1 expression was higher in oral melanomas. The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions.

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G1 cell cycle regulators in congenital melanocytic nevi. Comparison with acquired nevi and melanomas

Cited by 26 publications

References 39 publications

Cyclin D1 and D3 expression in melanocytic skin lesions

Cyclin D1 and D3 expression in melanocytic skin lesions

p16 Expression Is Lost in Severely Atypical Cellular Blue Nevi and Melanoma Compared to Conventional, Mildly, and Moderately Atypical Cellular Blue Nevi

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

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