Expression of sarcosine metabolism-related proteins in estrogen receptor negative breast cancer according to the androgen receptor and HER-2 status.
The aim of this study is to investigate the expression of sarcosine metabolism related proteins according to androgen receptor (AR) and HER-2 status in estrogen receptor (ER) negative breast cancer and to analyze its clinical implications. Tissue microarray was constructed for a total of 334 cases of ER negative breast cancer. Immunohistochemical stain was conducted for sarcosine metabolism related proteins such as glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX). There were 131 AR positive, 205 AR negative cases and 143 HER-2 positive, 193 HER-2 negative cases. When subdividing into four groups according to AR and HER-2 status, there were 55 AR(+)/HER-2(-) cases, 76 AR(+)/HER-2(+) cases, 67 AR(-)/HER-2(+) cases and 138 AR(-)/HER-2(-) cases. GNMT and PIPOX expression was highest in the AR(+)/HER-2(-) group while expressed lowest in the AR(-)/HER-2(-) group (P<0.001). Stromal PIPOX expression was highest in the AR(-)/HER-2(+) group and lowest in the AR(-)/HER-2(-) group (P=0.010). GNMT and PIPOX expression was higher in the AR positive group compared with those of AR negative group (P=0.001, and P<0.001, respectively), while tumoral and stromal PIPOX expression showed a significant association with HER-2 positivity (P=0.006, and P=0.005, respectively). AR positive group had the highest ratio of low sarcosine type while the AR negative group had the highest ratio of null type (P<0.001). In conclusion, ER negative breast cancer showed different expression of sarcosine metabolism related proteins according to AR and HER-2 status. GNMT and PIPOX expression was high in the AR positive group while tumoral and stromal PIPOX expression was high in the HER-2 positive group.
Department of Pathology, Gachon University Gil Medical Center Incheon, Korea.
Min Ju
MJ
Kim
Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
Woo Hee
WH
Jung
Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
Ja Seung
JS
Koo
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000201:enzymology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D050938:Glycine N-Methyltransferase / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011944:Receptors, Androgen / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis* / Q000172:deficiency; D012521:Sarcosine / Q000378:metabolism*; D050892:Sarcosine Dehydrogenase / Q000032:analysis; D050879:Sarcosine Oxidase / Q000032:analysis; D017154:Stromal Cells / Q000737:chemistry; D013997:Time Factors; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D050938:Glycine N-Methyltransferase; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D012521:Sarcosine; D050892:Sarcosine Dehydrogenase; D050879:Sarcosine Oxidase; C410798:AR protein, human; C494349:PIPOX protein, human; C494395:SARDH protein, human; C494510:GNMT protein, human; C508053:ERBB2 protein, human
Androgen receptor; breast cancer; sarcosine