Mammary Paget's disease and extra-mammary Paget's disease: two morphologically similar but biologically different diseases.
BACKGROUND
The cells of origin of mammary Paget's disease (MPD) and extra-mammary Paget's disease (EMPD) have been a controversial subject. The purpose of this study is to examine the expression of the human epidermal growth factor receptor 2 (HER2) pathway members in these two diseases.


METHODS
HER2, AKT, pAKT, PTEN, epidermal growth factor receptor (EGFR) and pEGFR were examined in 16 MPD and 14 EMPD cases. HER2 was graded on a scale from 0 to 3. A score of 3 was considered positive. For AKT, pAKT, PTEN, EGFR and pEGFR, a semi-quantitative scoring system was used. A score >100 was considered positive. Fisher's exact test was used to analyze the data.


RESULTS
HER2 was overexpressed in 87.5% MPD and 35.7% EMPD. While AKT was expressed in all cases, pAKT was expressed in 87.5% MPD and 92.9% EMPD. Both EGFR and pEGFR were negative in all cases. PTEN was positive in 62.5% MPD and 71.4% EMPD. For pAKT+ group, HER2-/PTEN+ was recorded in 0% MPD and 38.5% EMPD (P = .01).


CONCLUSIONS
In a subset of EMPD, AKT is not activated by HER2 overexpression or by loss of PTEN, which is not the case in MPD. These data suggest that these two diseases are biologically different.
Liu
Weiguo
W
Department of Pathology, State University of New York at Buffalo, NY, USA.
Iqbal
Jabad
J
Khoury
Thaer
T
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010145:Paget Disease, Extramammary / Q000378:metabolism* / Q000473:pathology; D010144:Paget's Disease, Mammary / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C494929:PTEN protein, human