The goal of this study was to see how significant it was in hepatocellular carcinoma for the expression of liver fatty acidbinding protein (L-FABP) to be downregulated (HCC). Methods: On tissue microarrays from 146 cases of HCC, immunohistochemical labelling for L-FABP was conducted. Further immunohistochemical staining was done on a representative whole-tissue section for each L-FABP-negative HCC to validate the downregulation of L-FABP expression and examine intratumoral heterogeneity of the staining pattern. Clinical data was acquired from the clinical files and histological slides were inspected. Immunohistochemical staining for cytokerati on tissue microarrays There was also a test for serum amyloid A (SAA). Clinicopathological characteristics of L-FABP-negative and L-FABP-positive HCC patients were compared. In addition, real-time reverse transcription polymerase chain reaction was used to examine L-FABP and GS gene expression in HCC and cholangiocarcinoma (CC) cell lines. For L-FABP-negative HCC cases, mutation analysis of HNF1A (encoding hepatocyte nuclear factor 1 (HNF1)) was done. Sixteen of the 146 HCC patients (10.9 percent) were negative for L-FABP. When we looked at the relationship between L-FABP downregulation and tumour size, we found that most cases of smaller HCC (less than 2 cm in diameter) had localised downregulation, while most cases of bigger HCC (more than 2 cm in diameter) had diffuse downregulation. The connection (P = 0.036) was statistically significant. The L-FABP-negative area commonly resembled a "nodule-in-nodule" look when the HCC was smaller. Tumor differentiation was much lower, and the frequency of intratumoral inflammation was significantly lower in L-FABP-negative cases than in L-FABP-positive cases in small HCC cases. Cases with FABP positivity (P = 0.032 and 0.009, respectively). L-FABP-negative instances of small HCC had a considerably greater frequency of -catenin and GS staining than L-FABP-positive cases of small HCC (P = 0.009 and P = 0.000, respectively). Four of the six HCC cell lines studied had increased L-FABP expression, whereas the remaining two had lower or no L-FABP expression. A mutation in exon 4 of HNF1A was found in two of the 16 L-FABP-negative HCC cases. Conclusion: L-FABP downregulation occurs in smaller HCCs due to phenotypic changes as the tumour progresses. Furthermore, this downregulation was linked to tumour differentiation and inflammation within the tumour.
Author(s) Details
Department of Pathology, Toranomon Hospital, Tokyo 105-8470, Japan.
Yoshihisa Takahashi
Department of Pathology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
Takeshi Fujii
Department of Pathology, Toranomon Hospital, Tokyo 105-8470, Japan.
Masanobu Kitagawa
Department of Comprehensive Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Toshio Fukusato
Department of Pathology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
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