title: Androgenic pathway in triple negative invasive ductal tumors: its correlation with tumor cell proliferation.
abstract: Triple negative breast cancer (TNBC) is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity. Patients with TNBC frequently undergo an aggressive clinical course due to the unavailability of specific targeted therapies. Androgen receptor (AR) was reported to be expressed in up to 60% of TNBC cases but there have been controversies as to the roles of androgen signaling through AR in TNBC. Therefore, in this study, we analyzed the status of AR in combination with androgen synthesizing enzymes (5α-reductase type 1 (5αR1) and 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5)] in order to further understand androgenic actions in TNBC. Androgen receptor, 5αR1, and 17βHSD5 were immunolocalized in a cohort of 203 TNBC patients from Thailand and Japan. We then correlated the findings with clinicopathological characteristics (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki-67 labeling index, disease-free survival, and overall survival) of the patients. Univariate analysis revealed that AR+/enzyme+ cases were associated with a significantly lower Ki-67 labeling index than AR-/enzyme- samples. Multivariate analysis indicated the presence of significant positive correlations between AR and enzyme status in tumor cells, and between tumor diameter, lymph node invasion, and distant metastasis. Significant negative correlations were also detected between Ki-67 labeling index and AR status (P = 0.04) or 5αR1 (P < 0.001). Cox proportional hazards analysis showed that Ki-67 labeling index and stage were the only factors predicting disease-free and overall survival of the patients, although univariate Kaplan-Meier analysis revealed AR/5αR1 negativity suggested a more adverse clinical course up to 80 months after surgery. These results suggest that the presence of androgen synthesizing pathways in addition to AR expression in tumor cells could confer a better clinical outcome through suppression of cell proliferation.
authors: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. kmcnamara@patholo2.med.tohoku.ac.jp
authors: Keely M
authors: KM
authors: McNamara
authors: Tomomi
authors: T
authors: Yoda
authors: Yasuhiro
authors: Y
authors: Miki
authors: Niramol
authors: N
authors: Chanplakorn
authors: Sansanee
authors: S
authors: Wongwaisayawan
authors: Pimpin
authors: P
authors: Incharoen
authors: Youwanush
authors: Y
authors: Kongdan
authors: Lin
authors: L
authors: Wang
authors: Kiyoshi
authors: K
authors: Takagi
authors: Takagi
authors: T
authors: Mayu
authors: Yasuhiro
authors: Y
authors: Nakamura
authors: Takashi
authors: T
authors: Suzuki
authors: Noriko
authors: N
authors: Nemoto
authors: Minoru
authors: M
authors: Miyashita
authors: Kentaro
authors: K
authors: Tamaki
authors: Takanori
authors: T
authors: Ishida
authors: Noriaki
authors: N
authors: Ohuchi
authors: Hironobu
authors: H
authors: Sasano
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D013785:Thailand
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase
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