Krüppel-like factor 4 (KLF4) is a
transcription factor regulating cell growth and differentiation. It has been postulated as a tumor suppressor gene in several
tumors including
colon cancer and
prostate cancer; whereas, it is activated in other
tumors such as
breast cancer and oropharyngeal
carcinomas. To understand the significance KLF4 on clinicopathologic implications in human
squamous cell carcinoma skin (SCC) progression, thirty six
formalin-fixed
paraffin-embedded samples of cutaneous SCC and 28 samples of
Bowen's disease were stained with anti-KLF4
antibodies. A semiquantitative evaluation of the degree of staining intensity and localization of expression were analyzed and correlated with histological and clinical features. Nuclear KLF4 staining was seen in differentiated epithelium including suprabasal keratinocyte of non-lesional skin. Strong nuclear KLF4 staining was observed in
tumor parts of both SCC and
Bowen's disease, when compared with their non-
tumor parts (p = 0.001). Increased expression of
KLF4 protein and
mRNA were found in
squamous cell carcinoma cell line studies and fresh skin tissue respectively, using western blotting and semi-quantitative real time polymerase chain reaction (PCR). SCC with moderately and poorly differentiated
tumors tend to have maturation independent (MI) staining pattern (p = 0.0004), compared to maturation dependent (MD) staining in well-differentiated
tumors. Finally, constitutive nuclear KLF4 staining pattern was significantly associated with moderately and poorly differentiated
tumors (p = 0.0006), and
tumor metastasis (p = 0.024). We propose that KLF4 expression is associated with human skin SCC progression and
metastases.