Loss of primary cilia correlates with cytologic severity in dysplastic melanocytic nevi.
BACKGROUND
Primary cilia are ubiquitously present in cell surface organelles with essential functions in cellular proliferation, differentiation and development. We have previously shown that cilia in melanoma in situ, invasive melanoma and metastatic melanoma are nearly completely lost, whereas benign nevi are ciliated. Dysplastic nevi (DN) have a wide range of histopathologic features from mild (low-grade) to severe (high-grade) cytologic atypia and represent a key clinical and histopathologic marker for melanomagenesis. We sought to identify whether cilia are retained in these melanocytic lesions and whether increasing degree of dysplasia correlates with loss of ciliation.


METHODS
We measured the percentage of ciliated melanocytes (ciliation index) in DN with mild (n = 9) and severe dysplasia (n = 10). We identified the primary cilium and basal bodies by immunofluorescence staining of sections with acetylated alpha-tubulin and gamma-tubulin, respectively.


RESULTS
Our results showed a significant decrease in the ciliation index from mild dysplastic (55%) to severe DN (14%) (p = 0.005).


CONCLUSIONS
These data support the hypothesis that primary cilium loss may play a role in the underlying biology of severe DN. The ciliation index is a novel quantitative tool that may increase the reproducibility in grading severity of dysplasia for diagnostic and clinical management of melanocytic neoplasms.
Section of Dermatopathology, Department of Dermatology and Pathology, Stanford University Medical Center, Stanford, CA, USA.
Ursula E
UE
Lang
Section of Dermatopathology, Department of Dermatology and Pathology, Stanford University Medical Center, Stanford, CA, USA.
Christine
C
Cheung
Section of Dermatopathology, Department of Dermatology and Pathology, Stanford University Medical Center, Stanford, CA, USA.
Eszter K
EK
Vladar
Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center, Stanford, CA, USA.|Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Susan M
SM
Swetter
Section of Dermatopathology, Department of Dermatology and Pathology, Stanford University Medical Center, Stanford, CA, USA.|Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center, Stanford, CA, USA.
Jinah
J
Kim
D000328:Adult; D000368:Aged; D002923:Cilia / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000378:metabolism* / Q000473:pathology*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*
dysplastic nevi; melanocytic; primary cilia