The Expression And Value Of P16, CDK4 And PCNA In Extramammary Paget's Disease

Objective:To study the expression of P16,CDK4 and PCNA and their correlation in extramammary Paget's disease(EMPD).Crocker,in 1889,described the first patient with extramammary Paget's disease.Extramammary Paget's disease (EMPD) is a rare malignant intraepithelial neoplasm of genital region,perineum or apocrine gland bearing skin in aged people.And it's frequently associated with underlying sweat gland or visceral malignancy.It's characterized by eczematous lesions in clinical and Paget's cells in histological.The histogenesis of EMPD has long been a subject of controversy.The tumour cells can invade the dermis and may metastasize via the lymphatic system.Lots of studies in recent years have revealed that uncontrolled cell cycle plays an important role in cell over-proliferation,which ultimately results in cell carcinogenesis.It is well known that cell cycle in eukaryotic cells is controlled by various complexes composed of cyclin and cyclin dependent kinase(CDK).As a novel protein identified by human,cyclin dependent kinase inhibitor (CDI) could combine with cyclin-CDK complexes,and inhibit the activity of those complexes.As a result, CDI arrests the transition from G1 phase to S phase in cell cycle and slowers the progression of cell proliferation,suggesting that acts as anti-oncogene product.It is generally accepted that P16 is an protein in CDI family,which could block the cell cycle at G1 phase by preventing Rb protein from phosphorylation.There have been a few speculations about whether the abnormal expression of P16 is relevant to the initiation and development of tumors.Some tumors found that they are short of P16,but others showed the overexpression of P16.CDK4 is essential for the transition from G1 phase to S phase in cell cycle and associates closely with the initiation of tumors.PCNA takes part in cell proliferation and it can be as the indexes of the cell proliferation.Extramammary Paget's disease which is a special skin tumor. However,the mechanism for Extramammary Paget's disease as well as its histological origin remains unclear.Up to date there's no report about expression or significance of P16,CDK4 and PCNA in Extramammary Paget's disease in literature.In this study,it's our objective that the results may provide a novel insight and means in clinical diagnosis and prognosis for Extramammary Paget's disease. Methods:Two-step immunohistochemistry technology was used to detect the expression of P16,CDK4 and PCNA in 34 cases of EMPD and 20 cases of normal skin tissues from skin surgery department.Laboratory data were analyzed statistically together with the related clinical-pathological data.Results:The positive expression rate of P16 in 34 cases of EMPD was 29.4%(10/34).The expression of P16 was apparently higher in EMPD than that in normal skin tissues.The difference was statistically significant(P<0.05).The Positive rates of PCNA and CDK4 expression in EMPD were 85.3%(29/34) and 67.6%(23/34) respectively.The expression of PCNA and CDK4 was apparently higher in EMPD than that in normal skin tissues(P<0.05). The Positive rates of PCNA and CDK4 were associated with lymph node metastasis(P<0.05).There was a positive correlation between PCNA and CDK4(P<0.05).The difference was statistically significant(P<0.05).Conclusion:P16 may play an important role in the cacinogenesis of EMPD. Overexpression of PCNA and CDK4 may contribute to the pathogenesis of EMPD,and it was correlated with lymph node metastasis.P16,CDK4 and PCNA may play an important role in the carcinogenesis and development of EMPD.P16,CDK4 and PCNA may be identified as a defining diagnostic marker and a potential gene therapeutic target in EMPD.The expression of P16 was not significantly correlated with age,gender,dermis infiltration,lymph node metastasis and recurrence in EMPD,indicating that the up-regulation expression of P16 is just related to oncogenesis of EMPD.It's just a biological parameter reflecting growth of EMPD. The high expression of CDK4 and PCNA in EMPD and the expression of CDK4 and PCNA was not significantly correlated with age,gender.However,they are correlated with dermis infiltration and lymph node metastasis in EMPD.The expression of CDK4 in EMPD closely relates to that of PCNA,indicating that they may play a cooperative role in this process.