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. 2003 Jul 7;89(1):140-5.
doi: 10.1038/sj.bjc.6601050.

FAK Overexpression Is Correlated With Tumour Invasiveness and Lymph Node Metastasis in Oesophageal Squamous Cell Carcinoma

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Free PMC article

FAK Overexpression Is Correlated With Tumour Invasiveness and Lymph Node Metastasis in Oesophageal Squamous Cell Carcinoma

T Miyazaki et al. Br J Cancer. .
Free PMC article

Abstract

Focal adhesion kinase (p125(FAK); 'FAK') is a tyrosine kinase that is localised to cellular focal adhesions and is associated with a number of other proteins, such as integrin adhesion receptors. We performed an immunohistochemical analysis of FAK protein expression to determine the relationship between FAK overexpression and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 91 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Seven human ESCC cell lines-TE-1, TE-2, TE-8, TE-13, TE-15, TT, and TTn-and one immortalized human keratinocyte cell line-HaCaT-were used in Western blot analysis. Immunostaining of FAK was seen in the cytoplasm of cancer cells, particularly in cells located in the invasive fronts of cancer nests. FAK overexpression was detected in 54 of the 91 patients (59.3%). Significant correlations were observed between FAK overexpression and cell differentiation (P=0.0057), depth of tumour invasion (P=0.0023), presence of regional lymph node metastasis (P=0.0097), number of lymph node metastases (P=0.0026), and disease stage (P=0.012). The survival rates of patients with FAK-overexpressing cancer were significantly lower than those of patients without FAK-overexpression cancer (P=0.006). The 5-year survival rate of patients without FAK overexpression was 69%, whereas that of patients with FAK overexpression was 38%. On Western blot analysis, FAK was expressed at a high level in TE-1, TE-8, TE-15, and TT cells, at a moderate level in TE-2 and TTn cells, and at a low level in TE13 and HaCaT cells. FAK phosphorylation at tyrosine 397 was demonstrated in proportion to the intensity of FAK in all cell lines except TE15 and HaCaT. In conclusion, FAK overexpression of ESCC was related to cell differentiation, tumour invasiveness, and lymph node metastasis. Consequently, patients with ESCC who had FAK overexpression had a poor prognosis.

Figures

Figure 1
Figure 1
Representative photomicrographs of tissue sections immunostained for FAK. (A) FAK was detected in the cytoplasm of the basal cells, parabasal cells, and leukocytes in normal oesophageal epithelium (right). Primary oesophageal cancer with FAK protein overexpression (× 100) (left). This case was regarded as FAK-overexpression (+). (B) FAK protein overexpression was detected in invasive cancer fronts, particularly in cells located in the peripheral layers of cancer cell nests (× 200). (C) Scattering small clusters of cancer cells have expressed FAK protein abundantly (× 100). (D) High-power view of the immunohistochemistry. FAK was detected in the cytoplasm of cancer cells (× 400).
Figure 2
Figure 2
Relationship between overall postoperative survival and FAK expression. FAK-overexpression (−) patients had a significantly more favourable prognosis than those with FAK overexpression (5-year survival rates: FAK overexpression (+), 38%; FAK overexpression (−), 69%; P=0.006).
Figure 3
Figure 3
Western blotting of cell extracts from seven ESCC lines. The figure shows the expression of FAK: 125 kDa; FAK phosphorylated at tyrosine 397 (P-FAK): 125 kDa and β-actin: 42 kDa (control).

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