Loss of Expression of the PTEN Gene Protein Product Is Associated with Poor Outcome in Breast Cancer

• Published in: Modern pathology 2001-07, Vol.14 (7), p.672-676
• Main Authors: Depowski, Peter L, Rosenthal, Seth I, Ross, Jeffrey S
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Automation; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell cycle; Cell growth; Cyclin-dependent kinases; Estrogens; Female; Humans; Immunohistochemistry; Kinases; Laboratory Medicine; Lymphatic system; Medical prognosis; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Mutation; original-article; Pathology; Phosphoric Monoester Hydrolases - biosynthesis; Prognosis; Protein expression; Proteins; PTEN; PTEN Phosphohydrolase; Stem cells; Survival Analysis; Tumor Suppressor Proteins; Tumorigenesis; Tumors; Womens health
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3880371

Introduction: The PTEN gene, a candidate tumor suppressor, is localized to chromosome 10q23 and shares extensive homology with cytoskeletal proteins auxilin and tensin. A high frequency of mutations at the PTEN locus has been described in a variety of neoplasms including breast cancer. However, the role of PTEN alternations and its association with outcome variables in breast neoplasia is not well established. Design: Formalin-fixed paraffin embedded tissues from 151 women (mean age 62 years, range 26–98) with primary diagnosis of invasive breast cancer were evaluated for PTEN protein expression by automated immunohistochemical methods. Slides were scored semi-quantitatively based on staining intensity and distribution, and results were compared with clinical pathologic parameters. The mean follow-up was 56 months (range 1–169). Results: Seventy-three (48%) of 151 breast tumors had loss of PTEN protein expression. On univariate analysis, loss of PTEN expression (P = .034), stage (P < .0001), node positive (P < .0001), and tumor grade (P = .002) were associated with disease-related death. Loss of PTEN expression also predicted lymph node metastasis (P < .0001), and correlated with loss of estrogen receptor staining (P = .040). Loss of PTEN did not correlate with stage, tumor grade, disease recurrence, or loss of progesterone receptor [although a trend was seen (P = .092). On multivariate analysis, stage (P < .0001), lymph node metastasis (P < .0001), and tumor grade (P = .002) correlated with survival. Conclusion: Loss of PTEN protein expression occurs commonly in breast cancer and correlates with disease related death, lymph node metastasis, and loss of estrogen receptor staining. Our results support the proposed role of PTEN as a candidate tumor suppressor in breast cancer and suggest a need for further study of this marker.