Immunohistochemical detection of phospho-Akt, phospho-BAD, HER2 and oestrogen receptors alpha and beta in Malaysian breast cancer patients.
Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-alpha, ER-beta, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-alpha, nuclear ER-beta, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-alpha expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-alpha or ER-beta was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-alpha expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.
Seow
Heng Fong
HF
Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia. shf@medic.upm.edu.my
Yip
Wai Kien
WK
Loh
Hui Woon
HW
Ithnin
Hairuszah
H
Por
Patricia
P
Rohaizak
Mohammad
M
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008296:Malaysia; D008875:Middle Aged; D009367:Neoplasm Staging; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; D051025:bcl-Associated Death Protein