Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

Net letter
doi: 10.4103/0378-6323.44341

Expression of cell cycle inhibitor p27 Kip1 in nevi and melanomas

Ayse Akman1 , M Akif Ciftcioglu2 , Caner Ozbey2 , Erkan Alpsoy1
1 Department of Dermatology and Venereology, Akdeniz University School of Medicine, Antalya, Turkey
2 Department of Pathology, Akdeniz University School of Medicine, Antalya, Turkey

Correspondence Address:
Ayse Akman
Department of Dermatology and Venereology, Akdeniz University School of Medicine, 07070 Antalya
How to cite this article:
Akman A, Ciftcioglu M A, Ozbey C, Alpsoy E. Expression of cell cycle inhibitor p27 Kip1 in nevi and melanomas. Indian J Dermatol Venereol Leprol 2008;74:551
Copyright: (C)2008 Indian Journal of Dermatology, Venereology, and Leprology


Cutaneous melanoma, the most aggressive skin tumor, is characterized by a multifactorial etiology. [1] Multiple genetic alterations including oncogens, tumor suppressor genes, and apoptosis-related genes can cause conversion of normal cells to cancer cells. [2] It has been suggested that proliferation and progression of cancer cells relate to abnormalities in various cell cycle regulators. Cell cycle is controlled by the regulators such as cyclins, cyclin-dependent kinases, and their inhibitors. P27 Kip1 is an important cyclin-dependent kinase inhibitor. It has crucial roles in cellular processes, which cause G1 arrest when overexpressed; and it functions as a tumor suppressor. [3]

There are conflicted data of p27 Kip1 expression in melanoma and dysplastic nevi. Besides low levels of p27 Kip1 , normal levels have also been reported to be associated with melanoma. [3] The aim of the present study was to investigate the expression of p27 Kip1 in melanocyctic lesions, and to identify its possible participation in melanoma progression.

Paraffin-embedded archival tissues from 45 patients with benign nevi (14), dysplastic nevi (15), and melanoma (16) diagnosed between 1991 and 2007 were evaluated for expression of p27 Kip1 by immunohistochemistry. Medical records were reviewed for each case for demographic data, as well as clinical and pathologic characteristics. All the samples were evaluated by the same pathologist, and strong nuclear staining was accepted as positive. In every sample, 10 fields were taken and 500 cells were evaluated for each field (40x). For every field, mean values were calculated for positive nuclear stained cells. Differences of P27 Kip1 expression between groups were evaluated by nonparametric test (Mann-Whitney U test). A value of P < 0.05 was considered significant.

Sixteen unrelated patients (6 women, 10 men; mean±SD age, 55.56±16.35 years) with melanoma; 15 patients (8 women, 7 men; mean±SD age, 36.73±7.71 years) with dysplastic nevi; and 14 patients (7 women, 7 men; mean±SD age, 28.71±6.79 years) with benign nevi were enrolled in the study. Expression of p27 Kip1 as the number of positive nuclei was 454.46±26.6 (91%) for the benign nevi, 452±21.7 (90.6%) for the dysplastic nevi, and 313±42.8 (62.6%) for the melanomas [Figure 1A],[Figure 1B]. A significant difference was observed in expression of p27 Kip1 between benign nevi and melanomas ( P < 0.001). There was also a significant difference in expression of p27 Kip1 between dysplastic nevi and melanomas ( P < 0.001) [Table - 1]. In melanoma cases, when the p27 Kip1 expression was analyzed according to the clinical and pathological features, it was seen that the expression was decreased in patients with metastasis, ulceration, increased tumor thickness, and male sex. But none of these changes were statistically significantly [Table - 2].

In the present study we found that p27 Kip1 expression was significantly lower in melanoma patients compared to patients with benign nevi and dysplastic nevi. Morgan et al, analyzed p27 Kip1 expression in 63 melanocyctic lesions (21 Spitz nevi, 21 compound nevi, and 21 melanomas). [4] They did not report any difference in p27 Kip1 staining. On the other hand, Ivan et al, also examined p27 Kip1 protein levels in melanocytic lesions (15 nevi, 18 dysplastic nevi, and 15 melanomas), and they reported lower expression levels of p27 Kip1 in melanoma cases. In agreement with this report for benign and dysplastic nevi, we found that p27 Kip1 was highly expressed in these lesions, supporting the notion that one important function of p27 Kip1 may be to regulate stillness in nevi cells. The level of p27 Kip1 has been shown to be regulated primarily at the post-transcriptional level through the ubiquitin-proteasome-mediated pathway. [5] The low level of p27 Kip1 in cancers is suggested to be due to an enhancement of its degradation and decreased stability. [3] A potential role of the extracellular matrix has also been proposed for inducing p27 Kip1 degradation in melanoma. [6]

Melanoma cell proliferation is an important parameter in determining the biological behavior of melanoma. p27 Kip1 has been suggested to have functions related to cell adhesion and may play a role in tumor invasion and metastasis by allowing cells to escape from the primary site. Florenes et al, have shown lower p27 Kip1 expression in thicker lesions in cases with nodular melanomas. In addition, they found that patients having tumors with fewer than 5% p27 Kip1 staining cells had a significantly higher risk of early relapse of their disease compared with those expressing moderate or high levels. [7]

Our results suggest that p27 Kip1 could play a critical role in the genesis and progression of melanoma, and future studies will be required to determine therapeutic importance of p27 Kip1 , in addition to the prognostic value.

Pinarbasi A, Savas B, Ciftcioglu MA, Alpsoy E. Cutaneous melanoma cases observed in Antalya from 1994 to 2003: Clinical and demographical properties. J Eur Acad Dermatol Venereol 2006;20:620-1.
[Google Scholar]
Zhang H, Rosdahl I. Expression of oncogenes, tumor suppressor, mismatch repair and apoptosis-related genes in primary and metastatic melanoma cells. Int J Oncol 2001;19:1149-53.
[Google Scholar]
Ivan D, Diwan AH, Esteva FJ, Prieto VG. Expression of cell cycle inhibitor p27(Kip1) and its activator Jab1 in melanocytic lesions. Mod Pathol 2004;17:811-18.
[Google Scholar]
Morgan MB, Cowper SE. Expression of p-27 (kip1) in nevi and melanomas. Am J Dermatopathol 1999;21:121-4.
[Google Scholar]
Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, et al . Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 1995;269:682-5.
[Google Scholar]
Henriet P, Zhong ZD, Brooks PC, Weinberg KI, DeClerck YA. Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1. Proc Natl Acad Sci USA 2000;97:10026-31.
[Google Scholar]
Florenes VA, Maelandsmo GM, Kerbel RS, Slingerland JM, Nesland JM, Holm R. Protein expression of the cell-cycle inhibitor p27Kip1 in malignant melanoma. Am J Pathol 1998;153:305-12.
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections