Loss of PTEN in high grade advanced stage triple negative breast ductal cancers in African American women

• Published in: Pathology, research and practice research and practice, 2018-05, Vol.214 (5), p.673-678
• Main Authors: Khan, Farhan, Esnakula, Ashwini, Ricks-Santi, Luisel J, Zafar, Rabia, Kanaan, Yasmine, Naab, Tammey
• Format: Article
• Language: English
• Subjects: Adult; African American; African Americans; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - pathology; Female; Humans; Mammalian target of rapamycin (mTOR); Middle Aged; Phosphatidyl inositol 3-kinase (PI3k)/AKT signal transduction pathway; Phosphatidylinositol 3-Kinases - metabolism; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; PTEN; PTEN Phosphohydrolase - genetics; TOR Serine-Threonine Kinases - metabolism; Triple Negative Breast Neoplasms - diagnosis; Triple Negative Breast Neoplasms - pathology; Triple-negative breast cancer
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2018.03.020

PTEN is a tumor suppressor gene that inhibits cell proliferation by inhibiting the phosphoinositide 3-kinase (PI3 K) signaling pathway. The significance of PTEN mutations resulting in variable PTEN expression and their impact on prognosis of breast cancer is not well established. The objective of our study was to correlate the immunohistochemical expression of PTEN in the four major subtypes of breast carcinoma (Luminal A, Luminal B, HER2 positive, and Triple Negative) in a population of 202 African-American (AA) females with other clinicopathological factors. Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 African-American females. Five micrometer sections were stained with a mouse monoclonal antibody against PTEN. The sections were evaluated for the intensity of cytoplasmic and nuclear reactivity. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). Loss of PTEN expression was associated with ER negative (p = 0.021), PR negative (p = 0.024) and triple negative (p = 0.0024) breast ductal cancers. It was marginally associated with distant metastasis (p = 0.074). There was no association between PTEN loss and recurrence-free survival or overall survival. In our study, a statistically significant association between PTEN loss and the triple negative breast cancers (TNBC) was found in AA women. PTEN inhibits PI3 K resulting in decreased activation of downstream effector, mammalian target of rapamycin (mTOR). Loss of PTEN results in cell proliferation through activation of mTOR. Targeted therapy with mTOR inhibitors might be useful in the treatment of TNBC.