Vimentin Emerges as a Powerful Prognostic Marker in Triple-Negative Breast Cancer

Triple-negative breast cancer is the most unforgiving form of the disease. Lacking the estrogen receptor, the progesterone receptor, and HER2, it cannot be reached by the hormonal therapies and HER2-targeted drugs that have transformed outcomes for other breast cancer subtypes. Now a retrospective cohort study from Dr. Cipto Mangunkusumo National General Hospital in Jakarta, published open access in Cancer Reports, points to a cytoskeletal protein as a potential beacon of prognosis in this aggressive cancer: vimentin, the hallmark intermediate filament of the epithelial-mesenchymal transition.

The research team, led by Erwin Danil Yulian, Teguh Herdadi, and Karl Heinz Leonhardt Rowika, examined archived tumor tissue from 29 female TNBC patients treated between 2017 and 2022. All patients had histologically confirmed triple-negative disease, defined as estrogen receptor expression of 1 percent or less, progesterone receptor expression of 1 percent or less, and HER2 scores of 0 to 1+ or 2+ with negative in situ hybridization. Using immunohistochemistry on formalin-fixed paraffin-embedded blocks, the investigators scored vimentin expression semiquantitatively, from 0 for no staining to 3+ for strong cytoplasmic staining in more than 10 percent of tumor cells. Crucially, only cytoplasmic staining within invasive tumor epithelial cells was counted; staining in stromal fibroblasts, endothelial cells, and inflammatory cells was excluded, since vimentin is constitutively expressed in normal mesenchymal cells and would otherwise confound the analysis.

The results were striking. Vimentin expression was detected in 22 of 29 cases, or 75.9 percent of the cohort. Among these positive cases, 14 showed strong 3+ expression, 6 showed moderate 2+ expression, and only 2 showed weak 1+ expression. When the researchers correlated expression status with overall survival, defined as the time from diagnosis to death from any cause or last follow-up, the association was statistically significant at p = 0.019. Of the 22 patients with positive vimentin expression, 19 experienced mortality events, while only 3 remained alive at the end of the observation period. In contrast, among the 7 patients with negative vimentin expression, only 3 experienced mortality events and 4 were alive at final follow-up.

Kaplan-Meier survival curves told the same story visually. Patients with positive vimentin expression had a mean survival time of 20.86 plus or minus 2.01 months, with a 95 percent confidence interval of 16.90 to 24.82 months. Those with negative expression survived a mean of 30.42 plus or minus 4.36 months, with a 95 percent confidence interval of 21.87 to 38.98 months. The log-rank test confirmed a significant difference between the two curves at p = 0.004, indicating that vimentin expression status meaningfully affects patient prognosis in this population.

What makes vimentin such a potent prognostic signal? The protein is a mesenchymal intermediate filament that sits at the heart of the epithelial-mesenchymal transition, a developmental program hijacked by cancer cells that enhances motility, invasiveness, and metastatic potential. EMT activation is regulated by transcription factors such as Snail, Twist, and Slug, and by signaling pathways including TGF-beta/SMAD, STAT3, and Wnt/beta-catenin. Overexpression of vimentin reflects EMT activation, cytoskeletal remodeling, and increased therapeutic resistance. Previous studies support the Indonesian findings: Xu and colleagues reported that vimentin overexpression in TNBC enhances invasion and anthracycline resistance, while Fedele and colleagues found that high vimentin levels doubled mortality risk and were associated with distant metastasis, particularly to the lung and brain.

Beyond survival, the study explored whether vimentin correlated with conventional clinicopathological characteristics. No significant associations were observed with age, body mass index, tumor size, lymph node status, histopathological grade, or clinical stage, all p values exceeding 0.05. However, vimentin expression showed a significant correlation with Ki-67 expression at p = 0.045, suggesting a link between EMT activation and proliferative activity. This association implies that proliferation and EMT may occur in parallel, as both are regulated by TGF-beta and beta-catenin signaling, which induce vimentin, CCND1, and MYC transcription. Inflammatory cytokines such as IL-6 and TNF-alpha further enhance this process via the JAK/STAT pathway, supporting tumor cell survival under oxidative and hypoxic stress.

In Cox regression analysis, vimentin expression emerged as an independent predictor of overall survival with a hazard ratio of 5.64 and a 95 percent confidence interval of 1.39 to 22.7 at p = 0.015. Adequate therapy was also significantly associated with survival, with a hazard ratio of 4.05 and a 95 percent confidence interval of 1.37 to 11.9 at p = 0.011. In contrast, conventional variables including tumor size, lymph node status, histopathological grade, and Ki-67 expression showed no statistically significant association with survival outcomes. This suggests that biological factors may play a more dominant role than anatomical characteristics in determining prognosis in TNBC, and that conventional clinicopathological variables may underestimate true biological aggressiveness.

The patient profile itself reveals much about TNBC in developing countries. Most patients were aged 40 years or older at 82.8 percent, had a normal body mass index below 25 at 82.8 percent, and presented with locally advanced disease at 72.4 percent. Nearly two-thirds had Grade III tumors, and 72.4 percent showed a high Ki-67 index of 20 percent or greater, indicating elevated proliferative activity consistent with basal-like TNBC biology. Late-stage presentation reflects persistent barriers to early detection in Indonesia, including low health literacy and limited access to diagnostic services, contributing directly to poorer survival outcomes since advanced TNBC typically has a 5-year survival below 50 percent.

The study has limitations that warrant caution. The cohort was small, drawn from a single institution, and dominated by locally advanced disease, which may not fully represent the broader spectrum of TNBC. Statistical power to detect significant associations was limited, and generalization to early-stage populations requires validation. Nevertheless, the findings suggest that incorporating vimentin immunostaining into routine diagnostic panels could enhance risk stratification and personalized management, particularly in tertiary centers. Patients with high vimentin levels may benefit from EMT-inhibitory strategies such as TGF-beta or STAT3 blockade, which are being explored in TNBC trials. Future prospective multicenter studies with larger and more heterogeneous cohorts are needed to confirm the prognostic significance of vimentin expression and to translate these findings into clinical practice.

Subject of Research: Triple-negative breast cancer

Article Title: The Prognostic Role of Vimentin Expression in Triple‐Negative Breast Cancer: A Retrospective Cohort Study

Article References: Danil Yulian, E., Hellyanti, T., & Rowika, K. H. L. (2026). The Prognostic Role of Vimentin Expression in Triple‐Negative Breast Cancer: A Retrospective Cohort Study. Cancer Reports, 9(10), Article e70632. https://doi.org/10.1002/cnr2.70632

Image Credits: AI Generated

DOI: 10.1002/cnr2.70632

Keywords: vimentin, triple-negative breast cancer, TNBC, epithelial-mesenchymal transition, EMT, Ki-67, immunohistochemistry, prognosis, overall survival, biomarker, Prognostic, Role