High expression of Ki-67 and cyclin D1 in invasive extramammary Paget's disease.
BACKGROUND
Invasive extramammary Paget's disease (EMPD) is commonly associated with a poor prognosis. Although early detection of micro invasion can improve the prognosis, diagnosis is not always straightforward in some EMPD cases. Several clinical studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicative of the invasiveness have yet to be well characterized.


OBJECTIVE
The purpose of this study was to identify a reliable immunohistochemical marker for predicting the risk of invasion and metastasis in EMPD cases.


METHODS
A total of 32 specimens from 23 primary EMPD cases were analyzed by immunohistochemical staining. In formalin-fixed, paraffin-embedded tissue sections, immunolabeling of tumor cells were scored by stain intensity on a four-tiered scale. Using antibodies against several tumor proliferation markers, such as Her2, p53, Ki-67, cyclin D1 and Bcl-2, we determined the correlation between the expression of these molecular markers and the types of EMPD lesions (in situ, invasive or metastatic).


RESULTS
In contrast to Her2, p53 and Bcl-2, which are similarly expressed among different types of lesions, Ki-67 and cyclin D1 are expressed at significantly higher levels in invasive lesions than in situ lesions (P<0.01 and P<0.05, respectively). Furthermore, the mean of the sum of Ki-67 and cyclin D1 expression scores was significantly higher in invasive lesions, compared to the scores obtained for in situ lesions. In addition, the difference was more significant (P<or=0.001) than each of these independent marker.


CONCLUSIONS
Combined high expression of Ki-67 and cyclin D1 was highly associated with invasive lesions of EMPD.
Aoyagi
Satoru
S
Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7 Kita-ku, Sapporo, Hokkaido 060-8638, Japan. saoyagi@med.hokudai.ac.jp
Akiyama
Masashi
M
Shimizu
Hiroshi
H
D000368:Aged; D000369:Aged, 80 and over; D001365:Axilla / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002455:Cell Division; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D005834:Genital Neoplasms, Male / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010145:Paget Disease, Extramammary / Q000453:epidemiology / Q000378:metabolism* / Q000556:secondary; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D012611:Scrotum / Q000473:pathology; D014844:Vulva / Q000473:pathology; D014846:Vulvar Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D056741:Cyclin D; D016213:Cyclins; D019394:Ki-67 Antigen