Expression of the Androgen Receptor, PAkt, and PPTEN in Breast Cancer and Their Potential in Prognostication

Overview

Journal Transl Oncol

Specialty Oncology

Date 2014 May 17

PMID 24831579

Citations 9

Authors

Aisha Sultana

Romana Idress

Zulfiqar Ali Naqvi

Iqbal Azam

Shaista Khan

Anwar Ali Siddiqui

El-Nasir Lalani

Affiliations

Soon will be listed here.

Abstract

Background: Importance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.

Methods: This study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥5years of follow-up (n=82).

Results: Expression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P<.001) and expressed ER (P=.002) and PR (P=.001). Patients with AR tumors had significantly higher OS (Mean OS=10.2±0.465years) compared to patients with AR tumors (Mean OS=5.8±0.348years) (P=.047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P=.020). Patients with AR /pAkt /pPTEN tumors, had increased OS (Mean OS=7.1±0.535years) compared to patients with AR/pAkt/pPTEN tumors (Mean OS=5.1±0.738years).

Conclusion: AR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa.

Citing Articles

A molecular switch from tumor suppressor to oncogene in ER+ve breast cancer: Role of androgen receptor, JAK-STAT, and lineage plasticity.

Asemota S, Effah W, Holt J, Johnson D, Cripe L, Ponnusamy S Proc Natl Acad Sci U S A. 2024; 121(40):e2406837121.

PMID: 39312663 PMC: 11459127. DOI: 10.1073/pnas.2406837121.

Impact of Androgen Receptor Expression and the AR:ER Ratio on the Survival Outcomes in the Diverse Subgroups of Vietnamese Breast Cancer: A Single Institutional Retrospective Cohort Analysis.

Phung H, Nguyen C, Mai N, Vu H, Pham K, Tran G Technol Cancer Res Treat. 2022; 21:15330338221080941.

PMID: 35379053 PMC: 8988687. DOI: 10.1177/15330338221080941.

Ethanol extract of (Rupr. & Maxim.) Harms induces liver cancer cell apoptosis through inhibiting NF-κB.

Zhao B, Zhu W, Han X, Li X, Lu Y, Cao X Transl Cancer Res. 2022; 9(2):1032-1043.

PMID: 35117448 PMC: 8798094. DOI: 10.21037/tcr.2020.01.02.

Selective androgen receptor modulators: the future of androgen therapy?.

Christiansen A, Lipshultz L, Hotaling J, Pastuszak A Transl Androl Urol. 2020; 9(Suppl 2):S135-S148.

PMID: 32257854 PMC: 7108998. DOI: 10.21037/tau.2019.11.02.

Androgen Receptor Is a Non-canonical Inhibitor of Wild-Type and Mutant Estrogen Receptors in Hormone Receptor-Positive Breast Cancers.

Ponnusamy S, Asemota S, Schwartzberg L, Guestini F, McNamara K, Pierobon M iScience. 2019; 21:341-358.

PMID: 31698248 PMC: 6889594. DOI: 10.1016/j.isci.2019.10.038.

References

Mishra A, Agrawal U, Negi S, Bansal A, Mohil R, Chintamani C . Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors. Indian J Med Res. 2012; 135(6):843-52. PMC: 3410212. View

Song G, Ouyang G, Bao S . The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005; 9(1):59-71. PMC: 6741304. DOI: 10.1111/j.1582-4934.2005.tb00337.x. View

Slamon D, Godolphin W, Jones L, Holt J, Wong S, Keith D . Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989; 244(4905):707-12. DOI: 10.1126/science.2470152. View

Peters A, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera M, Harris J . Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res. 2009; 69(15):6131-40. DOI: 10.1158/0008-5472.CAN-09-0452. View

Paez J, Sellers W . PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res. 2003; 115:145-67. View

Faheem M, Mahmood H, Khurram M, Qasim U, Irfan J . Estrogen receptor, progesterone receptor, and Her 2 Neu positivity and its association with tumour characteristics and menopausal status in a breast cancer cohort from northern Pakistan. Ecancermedicalscience. 2013; 6:283. PMC: 3530377. DOI: 10.3332/ecancer.2012.283. View

Langer M, Kubista E, Schemper M, Spona J . Androgen receptors, serum androgen levels and survival of breast cancer patients. Arch Gynecol Obstet. 1990; 247(4):203-9. DOI: 10.1007/BF02389545. View

Cleator S, Ahamed E, Coombes R, Palmieri C . A 2009 update on the treatment of patients with hormone receptor-positive breast cancer. Clin Breast Cancer. 2009; 9 Suppl 1:S6-S17. DOI: 10.3816/CBC.2009.s.001. View

Nagata Y, Lan K, Zhou X, Tan M, Esteva F, Sahin A . PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004; 6(2):117-27. DOI: 10.1016/j.ccr.2004.06.022. View

10.

Stambolic V, Suzuki A, de la Pompa J, Brothers G, Mirtsos C, Sasaki T . Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 1998; 95(1):29-39. DOI: 10.1016/s0092-8674(00)81780-8. View

11.

Stal O . Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer. 2002; 86(4):540-5. PMC: 2375266. DOI: 10.1038/sj.bjc.6600126. View

12.

Soiland H, Korner H, Skaland I, Janssen E, Gudlaugsson E, Varhaug J . Prognostic relevance of androgen receptor detection in operable breast cancer. J Surg Oncol. 2008; 98(7):551-8. DOI: 10.1002/jso.21156. View

13.

Aleskandarany M, Rakha E, Ahmed M, Powe D, Ellis I, Green A . Clinicopathologic and molecular significance of phospho-Akt expression in early invasive breast cancer. Breast Cancer Res Treat. 2010; 127(2):407-16. DOI: 10.1007/s10549-010-1012-y. View

14.

Schippinger W, Regitnig P, Dandachi N, Wernecke K, Bauernhofer T, Samonigg H . Evaluation of the prognostic significance of androgen receptor expression in metastatic breast cancer. Virchows Arch. 2006; 449(1):24-30. DOI: 10.1007/s00428-006-0213-6. View

15.

Nadji M, Gomez-Fernandez C, Ganjei-Azar P, Morales A . Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers. Am J Clin Pathol. 2005; 123(1):21-7. DOI: 10.1309/4wv79n2ghj3x1841. View

16.

Wang Y, Romigh T, He X, Tan M, Orloff M, Silverman R . Differential regulation of PTEN expression by androgen receptor in prostate and breast cancers. Oncogene. 2011; 30(42):4327-38. DOI: 10.1038/onc.2011.144. View

17.

Bhurgri Y, Kayani N, Faridi N, Pervez S, Usman A, Bhurgri H . Patho-epidemiology of breast cancer in Karachi '1995-1997'. Asian Pac J Cancer Prev. 2007; 8(2):215-20. View

18.

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W . Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785):177-82. DOI: 10.1126/science.3798106. View

19.

Park S, Park H, Koo J, Yang W, Kim S, Park B . Higher expression of androgen receptor is a significant predictor for better endocrine-responsiveness in estrogen receptor-positive breast cancers. Breast Cancer Res Treat. 2012; 133(1):311-20. DOI: 10.1007/s10549-011-1950-z. View

20.

Esteva F, Guo H, Zhang S, Santa-Maria C, Stone S, Lanchbury J . PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol. 2010; 177(4):1647-56. PMC: 2947262. DOI: 10.2353/ajpath.2010.090885. View