Expression of the transcriptional coregulator FHL2 in human breast cancer: a clinicopathologic study.
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 weak 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 independent predictor of survival.


CONCLUSIONS
The specific expression 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.
Gabriel
Boris
B
Department of Obstetrics and Gynecology and Molecular Gynecology, Center for Clinical Research, Freiburg University Medical Center, Freiburg, Germany. bGabriel@frk.ukl.uni-freiburg.de
Fischer
Dagmar-C
DC
Orlowska-Volk
M
M
zur Hausen
Axel
A
Schüle
Roland
R
Müller
Judith M
JM
Hasenburg
Annette
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D011944:Receptors, Androgen / Q000378:metabolism; D013534:Survival; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; D013629:Tamoxifen