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Journal of the Society for Gynecologic Investigation, Vol. 13, No. 1, 69-75 (2006)
DOI: 10.1016/j.jsgi.2005.10.001

Expression of the Transcriptional Coregulator FHL2 in Human Breast Cancer: A Clinicopathologic Study

Boris Gabriel, MD

Department of Obstetrics and Gynecology and Molecular Gynecology, Center for Clinical Research, and Department of Pathology, Freiburg University Medical Center, Freiburg, Germany; Department of Obstetrics and Gynecology, Heidelberg University Medical Center, Heidelberg, Germany bGabriel{at}frk.ukl.uni-freiburg.de

Dagmar-C Fischer, PhD

M. Orlowska-Volk, MD

Axel zur Hausen, MD

Roland Schüle, PhD

Judith M. Müller, PhD

Annettee Hasenburg, MD

Department of Obstetrics and Gynecology and Molecular Gynecology, Center for Clinical Research, and Department of Pathology, Freiburg University Medical Center, Freiburg, Germany; Department of Obstetrics and Gynecology, Heidelberg University Medical Center, Heidelberg, Germany

Objective: Although the Four and a Half LIM domain protein 2 (FHL2) has been suggested to play an important role in tumor development, this has not been investigated in breast cancer.

Methods: Paraffin-embedded tissues from patients (n = 85) with primary breast cancer were submitted to immunohistochemical investigation of FHL2 expression and subsequent correlation with clinicopathologic parameters and patient survival.

Results: The expression of FHL2 was confined to the cytoplasm of the tumor cells. Forty (47%) of 85 samples showed weake expression of FHL2, whereas high expression was found in 45 tumors (53%). A statistically significant positive correlation was observed between FHL2 and androgen receptor expression (P = .029). Patients with tumors expressing low amounts of FHL2 were characterized by a significantly better survival compared to those with high intratumoral FHL2 expression (P = .0215, log-rank test). The additional stratification according to adjuvant tamoxifen treatment revealed a significantly improved survival rate for patients receiving tamoxifen and being diagnosed with a tumor expressing high amounts of FHL2. This might indicate that tamoxifen is at least partially capable of reversing the negative prognostic impact of high FHL2 expression. Multivariate Cox regression analysis revealed FHL2 expression as a significant indepenent predictor of survival.

Conclusion: The specific in tumor tissue points to an important functional role of FHL2 in human breast cancer. Our survival data indicate that the expression of FHL2 in primary breast cancer is a potentially relevant prognostic factor. Further studies are warranted to elucidate whether analysis of FHL2 expression is suitable to predict response to antihormonal treatment with tamoxifen.

Key Words: FHL2 • breast cancer • prognostic marker • survival

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