Proliferation associated biomarkers in breast pathology
Preliminary data indicate that PHH3 has the potential to increase the sensitivity and specificity for the Luminal B subtype even further. Perhaps even more important, results indicate that PHH3 have a stronger prognostic value compared to Ki67. After analysis of receiver operating characteristics in our cohort with long term follow up data (n=88), the difference in overall survival of patients with PHH3 “high” (≥ 0.45 %) was 2,7 years shorter than patients with PHH3 “low” (< 0.45 %, p = 0.074). This difference was only 1,9 years when the same analysis was repeated for Ki67 at a cutoff of ≥20 % (p=0.448). With the imminent addition of more patients, the difference in survival in the PHH3 group is expected to be significant.
Johan Hartman is an associate professor of pathology and principal investigator at department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. Dr Hartman is a board certified surgical pathologist at the Karolinska University Laboratory, Southern Hospital (SÖS), Stockholm; the largest breast center in Scandinavia. Dr Hartman received his MD at Karolinska Institutet in 2008 and defended his thesis in tumor biology the same year. He has been main-supervisor for two completed PhD-degrees and is currently main-supervisor for three PhD-students. He is regularly lecturing for medical students, residents as well as for PhD-students at Karolinska Institutet. The main research focus of Dr Hartmans team is breast cancer therapy prediction, including digital image analysis in histopathology and computer-aided diagnosis, cancer genomics/transcriptomics and primary tumor cell cultures. Dr Hartman has received several awards such as the Alvarengas prize and the Anders Wall award for his research. He has more than 2800 citations. He is currently holding a clinical investigator award from the Swedish Cancer Society and has also research grants from Swedish Society for Medical Research, the Swedish Breast Cancer organisation and others.
Ma R, Karthik GM, Lövrot J, Haglund F, Rosin G, Katchy A, Zhang X, Viberg L, Jan Frisell J, Williams C, Linder S, Fredriksson I and Hartman J. Estrogen receptor b as a therapeutic target in breast cancer stem cells. Journal of the National Cancer Institute, in press, December 2016.
Rantalainen M, Klevebring D, Lindberg J, Ivansson E, Rosin G, Kis L, Celebioglu F, Fredriksson I, Czene K, Frisell J, Hartman J, Bergh J and Gronberg H. Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers. Scientific Reports. 2016 Nov 30;6:38037
Hosaka K, Yang Y, Seki T, Fischer C, Dubey O, Fredlund E, Hartman J, Religa P, Morikawa H, Ishii Y, Sasahara M, Larsson O, Cossu G, Cao R, Lim S, Cao Y. Pericyte-fibroblast transition promotes tumor growth and metastasis. Proc Natl Acad Sci U S A. 2016 Sep 7.
Stålhammar G, Martinez N F, Lippert M, Tobin N P, Mølholm I, Kis L, Rosin G, Rantalainen M, Pedersen L, Bergh J, Grunkin M and Hartman J. Digital image analysis outperforms manual biomarker assessment in breast cancer. Modern Pathology. 2016 Apr;29(4):318-29.
Karthik GM, Ma R, Lövrot J, Kis L, Lindh C, Blomquist L, Fredriksson I, Bergh J, Hartman J. mTOR inhibitors counteract tamoxifen-induced activation of breast cancer stem cells. Cancer Letters 2015 Oct 10;367(1):76-87.